AACR Annual Meeting 2011

ORLANDO – Heavy long-term beer drinking is associated with an increased risk of gastric cancer, particularly in people with a variant in a cluster of genes that metabolize alcohol, according to findings from the European Prospective Investigation into Cancer and Nutrition study.

More than 521,000 people in 10 European studies were part of the observational cohort EPIC study. Total consumption of 60 g (vs. less than 5 g) of pure ethanol/alcohol per day from all beverage types over an average of about 8-10 years was associated with a 65% increase in the risk of gastric cancer.

Photo credit: Len Rizzi/National Cancer Institute

The association was attributable to beer consumption, Eric J. Duell, Ph.D., reported at the annual meeting of the American Association for Cancer Research. That is, drinking 30 g of pure ethanol/alcohol per day strictly from beer (which equates to the alcohol level in about three beers) was associated with a 75% increase in risk. No significant increase in risk was seen with wine or liquor consumption.

Furthermore, an analysis of data from a nested case-control study within the EPIC cohort (the EurGast study) showed that in heavy beer drinkers with two copies of rs1230025 – an intergenic single nucleotide polymorphism (SNP) in the locus of the alcohol dehydrogenase gene cluster (ADH1) – the risk was increased by about 700%, compared with the risk in those who drank less and lacked the SNP (odds ratios, 8.72 and 1.29, respectively).

This interaction between the rs1230025 SNP (which itself confers a 30% increased risk of cancer) and beer consumption in relation to gastric cancer was statistically significant (P = .003), said Dr. Duell, senior epidemiologist in the cancer epidemiology research program at the Catalan Institute of Oncology in Barcelona.

The EPIC study enrolled adults aged 35-70 years from 1992 through 1998. Alcohol use and dietary factors were assessed by questionnaire. The current analysis included adjustment for age, center/country, sex, education level, smoking status, H. pylori infection (the main risk factor for gastric cancer, which is the second leading cause of death worldwide), diet, and total energy.

"This is the first study to see an association between this SNP and gastric cancer risk," Dr. Duell said, noting that although the findings need to be replicated in future studies, there are number of potential biological explanation for the associations.

For example, a build-up of acetaldehyde (a product of ethanol oxidation and a known carcinogen) in the stomach, excess nitrosamines (a known carcinogen found in beer), excess stomach bacteria resulting from atrophic gastritis (a known risk factor for gastric cancer), or a combination of these factors could be increasing risk, he said.

Dr. Duell had no relevant disclosures.

ORLANDO – Heavy long-term beer drinking is associated with an increased risk of gastric cancer, particularly in people with a variant in a cluster of genes that metabolize alcohol, according to findings from the European Prospective Investigation into Cancer and Nutrition study.

More than 521,000 people in 10 European studies were part of the observational cohort EPIC study. Total consumption of 60 g (vs. less than 5 g) of pure ethanol/alcohol per day from all beverage types over an average of about 8-10 years was associated with a 65% increase in the risk of gastric cancer.

Photo credit: Len Rizzi/National Cancer Institute

The association was attributable to beer consumption, Eric J. Duell, Ph.D., reported at the annual meeting of the American Association for Cancer Research. That is, drinking 30 g of pure ethanol/alcohol per day strictly from beer (which equates to the alcohol level in about three beers) was associated with a 75% increase in risk. No significant increase in risk was seen with wine or liquor consumption.

Furthermore, an analysis of data from a nested case-control study within the EPIC cohort (the EurGast study) showed that in heavy beer drinkers with two copies of rs1230025 – an intergenic single nucleotide polymorphism (SNP) in the locus of the alcohol dehydrogenase gene cluster (ADH1) – the risk was increased by about 700%, compared with the risk in those who drank less and lacked the SNP (odds ratios, 8.72 and 1.29, respectively).

This interaction between the rs1230025 SNP (which itself confers a 30% increased risk of cancer) and beer consumption in relation to gastric cancer was statistically significant (P = .003), said Dr. Duell, senior epidemiologist in the cancer epidemiology research program at the Catalan Institute of Oncology in Barcelona.

The EPIC study enrolled adults aged 35-70 years from 1992 through 1998. Alcohol use and dietary factors were assessed by questionnaire. The current analysis included adjustment for age, center/country, sex, education level, smoking status, H. pylori infection (the main risk factor for gastric cancer, which is the second leading cause of death worldwide), diet, and total energy.

"This is the first study to see an association between this SNP and gastric cancer risk," Dr. Duell said, noting that although the findings need to be replicated in future studies, there are number of potential biological explanation for the associations.

For example, a build-up of acetaldehyde (a product of ethanol oxidation and a known carcinogen) in the stomach, excess nitrosamines (a known carcinogen found in beer), excess stomach bacteria resulting from atrophic gastritis (a known risk factor for gastric cancer), or a combination of these factors could be increasing risk, he said.

Dr. Duell had no relevant disclosures.

ORLANDO – Heavy long-term beer drinking is associated with an increased risk of gastric cancer, particularly in people with a variant in a cluster of genes that metabolize alcohol, according to findings from the European Prospective Investigation into Cancer and Nutrition study.

More than 521,000 people in 10 European studies were part of the observational cohort EPIC study. Total consumption of 60 g (vs. less than 5 g) of pure ethanol/alcohol per day from all beverage types over an average of about 8-10 years was associated with a 65% increase in the risk of gastric cancer.

Photo credit: Len Rizzi/National Cancer Institute

The association was attributable to beer consumption, Eric J. Duell, Ph.D., reported at the annual meeting of the American Association for Cancer Research. That is, drinking 30 g of pure ethanol/alcohol per day strictly from beer (which equates to the alcohol level in about three beers) was associated with a 75% increase in risk. No significant increase in risk was seen with wine or liquor consumption.

Furthermore, an analysis of data from a nested case-control study within the EPIC cohort (the EurGast study) showed that in heavy beer drinkers with two copies of rs1230025 – an intergenic single nucleotide polymorphism (SNP) in the locus of the alcohol dehydrogenase gene cluster (ADH1) – the risk was increased by about 700%, compared with the risk in those who drank less and lacked the SNP (odds ratios, 8.72 and 1.29, respectively).

This interaction between the rs1230025 SNP (which itself confers a 30% increased risk of cancer) and beer consumption in relation to gastric cancer was statistically significant (P = .003), said Dr. Duell, senior epidemiologist in the cancer epidemiology research program at the Catalan Institute of Oncology in Barcelona.

The EPIC study enrolled adults aged 35-70 years from 1992 through 1998. Alcohol use and dietary factors were assessed by questionnaire. The current analysis included adjustment for age, center/country, sex, education level, smoking status, H. pylori infection (the main risk factor for gastric cancer, which is the second leading cause of death worldwide), diet, and total energy.

"This is the first study to see an association between this SNP and gastric cancer risk," Dr. Duell said, noting that although the findings need to be replicated in future studies, there are number of potential biological explanation for the associations.

For example, a build-up of acetaldehyde (a product of ethanol oxidation and a known carcinogen) in the stomach, excess nitrosamines (a known carcinogen found in beer), excess stomach bacteria resulting from atrophic gastritis (a known risk factor for gastric cancer), or a combination of these factors could be increasing risk, he said.

Dr. Duell had no relevant disclosures.

ORLANDO – Heavy long-term beer drinking is associated with an increased risk of gastric cancer, particularly in people with a variant in a cluster of genes that metabolize alcohol, according to findings from the European Prospective Investigation into Cancer and Nutrition study.

More than 521,000 people in 10 European studies were part of the observational cohort EPIC study. Total consumption of 60 g (vs. less than 5 g) of pure ethanol/alcohol per day from all beverage types over an average of about 8-10 years was associated with a 65% increase in the risk of gastric cancer.

Photo credit: Len Rizzi/National Cancer Institute

The association was attributable to beer consumption, Eric J. Duell, Ph.D., reported at the annual meeting of the American Association for Cancer Research. That is, drinking 30 g of pure ethanol/alcohol per day strictly from beer (which equates to the alcohol level in about three beers) was associated with a 75% increase in risk. No significant increase in risk was seen with wine or liquor consumption.

Furthermore, an analysis of data from a nested case-control study within the EPIC cohort (the EurGast study) showed that in heavy beer drinkers with two copies of rs1230025 – an intergenic single nucleotide polymorphism (SNP) in the locus of the alcohol dehydrogenase gene cluster (ADH1) – the risk was increased by about 700%, compared with the risk in those who drank less and lacked the SNP (odds ratios, 8.72 and 1.29, respectively).

This interaction between the rs1230025 SNP (which itself confers a 30% increased risk of cancer) and beer consumption in relation to gastric cancer was statistically significant (P = .003), said Dr. Duell, senior epidemiologist in the cancer epidemiology research program at the Catalan Institute of Oncology in Barcelona.

The EPIC study enrolled adults aged 35-70 years from 1992 through 1998. Alcohol use and dietary factors were assessed by questionnaire. The current analysis included adjustment for age, center/country, sex, education level, smoking status, H. pylori infection (the main risk factor for gastric cancer, which is the second leading cause of death worldwide), diet, and total energy.

"This is the first study to see an association between this SNP and gastric cancer risk," Dr. Duell said, noting that although the findings need to be replicated in future studies, there are number of potential biological explanation for the associations.

For example, a build-up of acetaldehyde (a product of ethanol oxidation and a known carcinogen) in the stomach, excess nitrosamines (a known carcinogen found in beer), excess stomach bacteria resulting from atrophic gastritis (a known risk factor for gastric cancer), or a combination of these factors could be increasing risk, he said.

Dr. Duell had no relevant disclosures.

ORLANDO – Heavy long-term beer drinking is associated with an increased risk of gastric cancer, particularly in people with a variant in a cluster of genes that metabolize alcohol, according to findings from the European Prospective Investigation into Cancer and Nutrition study.

More than 521,000 people in 10 European studies were part of the observational cohort EPIC study. Total consumption of 60 g (vs. less than 5 g) of pure ethanol/alcohol per day from all beverage types over an average of about 8-10 years was associated with a 65% increase in the risk of gastric cancer.

Photo credit: Len Rizzi/National Cancer Institute

The association was attributable to beer consumption, Eric J. Duell, Ph.D., reported at the annual meeting of the American Association for Cancer Research. That is, drinking 30 g of pure ethanol/alcohol per day strictly from beer (which equates to the alcohol level in about three beers) was associated with a 75% increase in risk. No significant increase in risk was seen with wine or liquor consumption.

Furthermore, an analysis of data from a nested case-control study within the EPIC cohort (the EurGast study) showed that in heavy beer drinkers with two copies of rs1230025 – an intergenic single nucleotide polymorphism (SNP) in the locus of the alcohol dehydrogenase gene cluster (ADH1) – the risk was increased by about 700%, compared with the risk in those who drank less and lacked the SNP (odds ratios, 8.72 and 1.29, respectively).

This interaction between the rs1230025 SNP (which itself confers a 30% increased risk of cancer) and beer consumption in relation to gastric cancer was statistically significant (P = .003), said Dr. Duell, senior epidemiologist in the cancer epidemiology research program at the Catalan Institute of Oncology in Barcelona.

The EPIC study enrolled adults aged 35-70 years from 1992 through 1998. Alcohol use and dietary factors were assessed by questionnaire. The current analysis included adjustment for age, center/country, sex, education level, smoking status, H. pylori infection (the main risk factor for gastric cancer, which is the second leading cause of death worldwide), diet, and total energy.

"This is the first study to see an association between this SNP and gastric cancer risk," Dr. Duell said, noting that although the findings need to be replicated in future studies, there are number of potential biological explanation for the associations.

For example, a build-up of acetaldehyde (a product of ethanol oxidation and a known carcinogen) in the stomach, excess nitrosamines (a known carcinogen found in beer), excess stomach bacteria resulting from atrophic gastritis (a known risk factor for gastric cancer), or a combination of these factors could be increasing risk, he said.

Dr. Duell had no relevant disclosures.

ORLANDO – Heavy long-term beer drinking is associated with an increased risk of gastric cancer, particularly in people with a variant in a cluster of genes that metabolize alcohol, according to findings from the European Prospective Investigation into Cancer and Nutrition study.

More than 521,000 people in 10 European studies were part of the observational cohort EPIC study. Total consumption of 60 g (vs. less than 5 g) of pure ethanol/alcohol per day from all beverage types over an average of about 8-10 years was associated with a 65% increase in the risk of gastric cancer.

Photo credit: Len Rizzi/National Cancer Institute

The association was attributable to beer consumption, Eric J. Duell, Ph.D., reported at the annual meeting of the American Association for Cancer Research. That is, drinking 30 g of pure ethanol/alcohol per day strictly from beer (which equates to the alcohol level in about three beers) was associated with a 75% increase in risk. No significant increase in risk was seen with wine or liquor consumption.

Furthermore, an analysis of data from a nested case-control study within the EPIC cohort (the EurGast study) showed that in heavy beer drinkers with two copies of rs1230025 – an intergenic single nucleotide polymorphism (SNP) in the locus of the alcohol dehydrogenase gene cluster (ADH1) – the risk was increased by about 700%, compared with the risk in those who drank less and lacked the SNP (odds ratios, 8.72 and 1.29, respectively).

This interaction between the rs1230025 SNP (which itself confers a 30% increased risk of cancer) and beer consumption in relation to gastric cancer was statistically significant (P = .003), said Dr. Duell, senior epidemiologist in the cancer epidemiology research program at the Catalan Institute of Oncology in Barcelona.

The EPIC study enrolled adults aged 35-70 years from 1992 through 1998. Alcohol use and dietary factors were assessed by questionnaire. The current analysis included adjustment for age, center/country, sex, education level, smoking status, H. pylori infection (the main risk factor for gastric cancer, which is the second leading cause of death worldwide), diet, and total energy.

"This is the first study to see an association between this SNP and gastric cancer risk," Dr. Duell said, noting that although the findings need to be replicated in future studies, there are number of potential biological explanation for the associations.

For example, a build-up of acetaldehyde (a product of ethanol oxidation and a known carcinogen) in the stomach, excess nitrosamines (a known carcinogen found in beer), excess stomach bacteria resulting from atrophic gastritis (a known risk factor for gastric cancer), or a combination of these factors could be increasing risk, he said.

Dr. Duell had no relevant disclosures.

ORLANDO – Heavy long-term beer drinking is associated with an increased risk of gastric cancer, particularly in people with a variant in a cluster of genes that metabolize alcohol, according to findings from the European Prospective Investigation into Cancer and Nutrition study.

More than 521,000 people in 10 European studies were part of the observational cohort EPIC study. Total consumption of 60 g (vs. less than 5 g) of pure ethanol/alcohol per day from all beverage types over an average of about 8-10 years was associated with a 65% increase in the risk of gastric cancer.

Photo credit: Len Rizzi/National Cancer Institute

The association was attributable to beer consumption, Eric J. Duell, Ph.D., reported at the annual meeting of the American Association for Cancer Research. That is, drinking 30 g of pure ethanol/alcohol per day strictly from beer (which equates to the alcohol level in about three beers) was associated with a 75% increase in risk. No significant increase in risk was seen with wine or liquor consumption.

Furthermore, an analysis of data from a nested case-control study within the EPIC cohort (the EurGast study) showed that in heavy beer drinkers with two copies of rs1230025 – an intergenic single nucleotide polymorphism (SNP) in the locus of the alcohol dehydrogenase gene cluster (ADH1) – the risk was increased by about 700%, compared with the risk in those who drank less and lacked the SNP (odds ratios, 8.72 and 1.29, respectively).

This interaction between the rs1230025 SNP (which itself confers a 30% increased risk of cancer) and beer consumption in relation to gastric cancer was statistically significant (P = .003), said Dr. Duell, senior epidemiologist in the cancer epidemiology research program at the Catalan Institute of Oncology in Barcelona.

The EPIC study enrolled adults aged 35-70 years from 1992 through 1998. Alcohol use and dietary factors were assessed by questionnaire. The current analysis included adjustment for age, center/country, sex, education level, smoking status, H. pylori infection (the main risk factor for gastric cancer, which is the second leading cause of death worldwide), diet, and total energy.

"This is the first study to see an association between this SNP and gastric cancer risk," Dr. Duell said, noting that although the findings need to be replicated in future studies, there are number of potential biological explanation for the associations.

For example, a build-up of acetaldehyde (a product of ethanol oxidation and a known carcinogen) in the stomach, excess nitrosamines (a known carcinogen found in beer), excess stomach bacteria resulting from atrophic gastritis (a known risk factor for gastric cancer), or a combination of these factors could be increasing risk, he said.

Dr. Duell had no relevant disclosures.

ORLANDO – Heavy long-term beer drinking is associated with an increased risk of gastric cancer, particularly in people with a variant in a cluster of genes that metabolize alcohol, according to findings from the European Prospective Investigation into Cancer and Nutrition study.

More than 521,000 people in 10 European studies were part of the observational cohort EPIC study. Total consumption of 60 g (vs. less than 5 g) of pure ethanol/alcohol per day from all beverage types over an average of about 8-10 years was associated with a 65% increase in the risk of gastric cancer.

Photo credit: Len Rizzi/National Cancer Institute

The association was attributable to beer consumption, Eric J. Duell, Ph.D., reported at the annual meeting of the American Association for Cancer Research. That is, drinking 30 g of pure ethanol/alcohol per day strictly from beer (which equates to the alcohol level in about three beers) was associated with a 75% increase in risk. No significant increase in risk was seen with wine or liquor consumption.

Furthermore, an analysis of data from a nested case-control study within the EPIC cohort (the EurGast study) showed that in heavy beer drinkers with two copies of rs1230025 – an intergenic single nucleotide polymorphism (SNP) in the locus of the alcohol dehydrogenase gene cluster (ADH1) – the risk was increased by about 700%, compared with the risk in those who drank less and lacked the SNP (odds ratios, 8.72 and 1.29, respectively).

This interaction between the rs1230025 SNP (which itself confers a 30% increased risk of cancer) and beer consumption in relation to gastric cancer was statistically significant (P = .003), said Dr. Duell, senior epidemiologist in the cancer epidemiology research program at the Catalan Institute of Oncology in Barcelona.

The EPIC study enrolled adults aged 35-70 years from 1992 through 1998. Alcohol use and dietary factors were assessed by questionnaire. The current analysis included adjustment for age, center/country, sex, education level, smoking status, H. pylori infection (the main risk factor for gastric cancer, which is the second leading cause of death worldwide), diet, and total energy.

"This is the first study to see an association between this SNP and gastric cancer risk," Dr. Duell said, noting that although the findings need to be replicated in future studies, there are number of potential biological explanation for the associations.

For example, a build-up of acetaldehyde (a product of ethanol oxidation and a known carcinogen) in the stomach, excess nitrosamines (a known carcinogen found in beer), excess stomach bacteria resulting from atrophic gastritis (a known risk factor for gastric cancer), or a combination of these factors could be increasing risk, he said.

Dr. Duell had no relevant disclosures.

ORLANDO – Heavy long-term beer drinking is associated with an increased risk of gastric cancer, particularly in people with a variant in a cluster of genes that metabolize alcohol, according to findings from the European Prospective Investigation into Cancer and Nutrition study.

More than 521,000 people in 10 European studies were part of the observational cohort EPIC study. Total consumption of 60 g (vs. less than 5 g) of pure ethanol/alcohol per day from all beverage types over an average of about 8-10 years was associated with a 65% increase in the risk of gastric cancer.

Photo credit: Len Rizzi/National Cancer Institute

The association was attributable to beer consumption, Eric J. Duell, Ph.D., reported at the annual meeting of the American Association for Cancer Research. That is, drinking 30 g of pure ethanol/alcohol per day strictly from beer (which equates to the alcohol level in about three beers) was associated with a 75% increase in risk. No significant increase in risk was seen with wine or liquor consumption.

Furthermore, an analysis of data from a nested case-control study within the EPIC cohort (the EurGast study) showed that in heavy beer drinkers with two copies of rs1230025 – an intergenic single nucleotide polymorphism (SNP) in the locus of the alcohol dehydrogenase gene cluster (ADH1) – the risk was increased by about 700%, compared with the risk in those who drank less and lacked the SNP (odds ratios, 8.72 and 1.29, respectively).

This interaction between the rs1230025 SNP (which itself confers a 30% increased risk of cancer) and beer consumption in relation to gastric cancer was statistically significant (P = .003), said Dr. Duell, senior epidemiologist in the cancer epidemiology research program at the Catalan Institute of Oncology in Barcelona.

The EPIC study enrolled adults aged 35-70 years from 1992 through 1998. Alcohol use and dietary factors were assessed by questionnaire. The current analysis included adjustment for age, center/country, sex, education level, smoking status, H. pylori infection (the main risk factor for gastric cancer, which is the second leading cause of death worldwide), diet, and total energy.

"This is the first study to see an association between this SNP and gastric cancer risk," Dr. Duell said, noting that although the findings need to be replicated in future studies, there are number of potential biological explanation for the associations.

For example, a build-up of acetaldehyde (a product of ethanol oxidation and a known carcinogen) in the stomach, excess nitrosamines (a known carcinogen found in beer), excess stomach bacteria resulting from atrophic gastritis (a known risk factor for gastric cancer), or a combination of these factors could be increasing risk, he said.

Dr. Duell had no relevant disclosures.

ORLANDO – Diabetes appears to be associated with an increased risk of several types of cancer and with an increased risk of cancer-related mortality in both men and women, findings from a large prospective study have shown.

Incidence rates for both diseases are increasing worldwide, and although prior research has demonstrated a decreased risk for prostate cancer in men with diabetes – perhaps due to the lower testosterone levels associated with diabetes – the association between diabetes and other cancers has not been well studied, Gabriel Lai, Ph.D., said at the annual meeting of the American Association for Cancer Research.

To better characterize the association between the two diseases, Dr. Lai and his colleagues analyzed data from the nearly 300,000 men and 200,000 women aged 50-71 years who participated in a diet and health study by the National Institutes of Health and AARP. After 11 years of follow-up, about 13,000 of the men and nearly 6,500 of the women in the study had died of cancer.

A modest inverse association between diabetes and total incident cancer was observed in men (hazard ratio, 0.96), but this stemmed largely from prostate cancer, as expected based on the prior research on diabetes and prostate cancer. In the current study, prostate cancer accounted for 42% of all the cancers in men, and when it was excluded from the analysis, diabetes was found to be positively associated with cancer in men (HR, 1.08) and with cancer mortality in men (HR, 1.20), said Dr. Lai, a cancer prevention fellow at the National Cancer Institute.

Diabetes also was found to have a modest association with cancer in women (HR, 1.06) and with cancer mortality in women (HR, 1.15).

Statistically significant associations were observed for cancers of the colon, rectum, and liver in both men and women (HR, 1.15, 1.28, and 2.40, respectively); for the pancreas and urinary bladder in men (HR, 1.47 and 1.10, respectively); and for the stomach, anus, and corpus and uterus in women (HR, 1.74, 2.44, and 1.20, respectively). The risk estimates for cancers of the pancreas and urinary bladder in women with diabetes were similar to those in men, and the risk estimate for stomach cancer in men was similar to that in women, but these did not reach statistical significance, Dr. Lai said.

No association between diabetes and lung, skin, or other cancers was observed, he noted.

Diabetes in the NIH-AARP study was assessed by self-report in the predominantly white, non-Hispanic cohort, and all analyses included adjustment for age; education; body mass index; smoking status; self-reported health status; physical activity; vitamin supplement use; alcohol intake; diet (fruit, vegetable, and meat consumption); family history of cancer; and – among women – hormonal therapy.

The findings provide additional evidence that abnormal insulin and glucose signaling contribute to cancer risk, and suggest that in addition to myriad other benefits, avoiding diabetes through diet, exercise, and maintenance of healthy body weight potentially reduces the risk for cancer development and mortality, Dr. Lai said.

Further study is needed to elucidate the biologic mechanisms of the association between diabetes and cancer, he concluded.

Dr. Lai said he had no relevant financial disclosures. The study was sponsored by the National Cancer Institute.

ORLANDO – Diabetes appears to be associated with an increased risk of several types of cancer and with an increased risk of cancer-related mortality in both men and women, findings from a large prospective study have shown.

Incidence rates for both diseases are increasing worldwide, and although prior research has demonstrated a decreased risk for prostate cancer in men with diabetes – perhaps due to the lower testosterone levels associated with diabetes – the association between diabetes and other cancers has not been well studied, Gabriel Lai, Ph.D., said at the annual meeting of the American Association for Cancer Research.

To better characterize the association between the two diseases, Dr. Lai and his colleagues analyzed data from the nearly 300,000 men and 200,000 women aged 50-71 years who participated in a diet and health study by the National Institutes of Health and AARP. After 11 years of follow-up, about 13,000 of the men and nearly 6,500 of the women in the study had died of cancer.

A modest inverse association between diabetes and total incident cancer was observed in men (hazard ratio, 0.96), but this stemmed largely from prostate cancer, as expected based on the prior research on diabetes and prostate cancer. In the current study, prostate cancer accounted for 42% of all the cancers in men, and when it was excluded from the analysis, diabetes was found to be positively associated with cancer in men (HR, 1.08) and with cancer mortality in men (HR, 1.20), said Dr. Lai, a cancer prevention fellow at the National Cancer Institute.

Diabetes also was found to have a modest association with cancer in women (HR, 1.06) and with cancer mortality in women (HR, 1.15).

Statistically significant associations were observed for cancers of the colon, rectum, and liver in both men and women (HR, 1.15, 1.28, and 2.40, respectively); for the pancreas and urinary bladder in men (HR, 1.47 and 1.10, respectively); and for the stomach, anus, and corpus and uterus in women (HR, 1.74, 2.44, and 1.20, respectively). The risk estimates for cancers of the pancreas and urinary bladder in women with diabetes were similar to those in men, and the risk estimate for stomach cancer in men was similar to that in women, but these did not reach statistical significance, Dr. Lai said.

No association between diabetes and lung, skin, or other cancers was observed, he noted.

Diabetes in the NIH-AARP study was assessed by self-report in the predominantly white, non-Hispanic cohort, and all analyses included adjustment for age; education; body mass index; smoking status; self-reported health status; physical activity; vitamin supplement use; alcohol intake; diet (fruit, vegetable, and meat consumption); family history of cancer; and – among women – hormonal therapy.

The findings provide additional evidence that abnormal insulin and glucose signaling contribute to cancer risk, and suggest that in addition to myriad other benefits, avoiding diabetes through diet, exercise, and maintenance of healthy body weight potentially reduces the risk for cancer development and mortality, Dr. Lai said.

Further study is needed to elucidate the biologic mechanisms of the association between diabetes and cancer, he concluded.

Dr. Lai said he had no relevant financial disclosures. The study was sponsored by the National Cancer Institute.

ORLANDO – Diabetes appears to be associated with an increased risk of several types of cancer and with an increased risk of cancer-related mortality in both men and women, findings from a large prospective study have shown.

Incidence rates for both diseases are increasing worldwide, and although prior research has demonstrated a decreased risk for prostate cancer in men with diabetes – perhaps due to the lower testosterone levels associated with diabetes – the association between diabetes and other cancers has not been well studied, Gabriel Lai, Ph.D., said at the annual meeting of the American Association for Cancer Research.

To better characterize the association between the two diseases, Dr. Lai and his colleagues analyzed data from the nearly 300,000 men and 200,000 women aged 50-71 years who participated in a diet and health study by the National Institutes of Health and AARP. After 11 years of follow-up, about 13,000 of the men and nearly 6,500 of the women in the study had died of cancer.

A modest inverse association between diabetes and total incident cancer was observed in men (hazard ratio, 0.96), but this stemmed largely from prostate cancer, as expected based on the prior research on diabetes and prostate cancer. In the current study, prostate cancer accounted for 42% of all the cancers in men, and when it was excluded from the analysis, diabetes was found to be positively associated with cancer in men (HR, 1.08) and with cancer mortality in men (HR, 1.20), said Dr. Lai, a cancer prevention fellow at the National Cancer Institute.

Diabetes also was found to have a modest association with cancer in women (HR, 1.06) and with cancer mortality in women (HR, 1.15).

Statistically significant associations were observed for cancers of the colon, rectum, and liver in both men and women (HR, 1.15, 1.28, and 2.40, respectively); for the pancreas and urinary bladder in men (HR, 1.47 and 1.10, respectively); and for the stomach, anus, and corpus and uterus in women (HR, 1.74, 2.44, and 1.20, respectively). The risk estimates for cancers of the pancreas and urinary bladder in women with diabetes were similar to those in men, and the risk estimate for stomach cancer in men was similar to that in women, but these did not reach statistical significance, Dr. Lai said.

No association between diabetes and lung, skin, or other cancers was observed, he noted.

Diabetes in the NIH-AARP study was assessed by self-report in the predominantly white, non-Hispanic cohort, and all analyses included adjustment for age; education; body mass index; smoking status; self-reported health status; physical activity; vitamin supplement use; alcohol intake; diet (fruit, vegetable, and meat consumption); family history of cancer; and – among women – hormonal therapy.

The findings provide additional evidence that abnormal insulin and glucose signaling contribute to cancer risk, and suggest that in addition to myriad other benefits, avoiding diabetes through diet, exercise, and maintenance of healthy body weight potentially reduces the risk for cancer development and mortality, Dr. Lai said.

Further study is needed to elucidate the biologic mechanisms of the association between diabetes and cancer, he concluded.

Dr. Lai said he had no relevant financial disclosures. The study was sponsored by the National Cancer Institute.

ORLANDO – Diabetes appears to be associated with an increased risk of several types of cancer and with an increased risk of cancer-related mortality in both men and women, findings from a large prospective study have shown.

Incidence rates for both diseases are increasing worldwide, and although prior research has demonstrated a decreased risk for prostate cancer in men with diabetes – perhaps due to the lower testosterone levels associated with diabetes – the association between diabetes and other cancers has not been well studied, Gabriel Lai, Ph.D., said at the annual meeting of the American Association for Cancer Research.

To better characterize the association between the two diseases, Dr. Lai and his colleagues analyzed data from the nearly 300,000 men and 200,000 women aged 50-71 years who participated in a diet and health study by the National Institutes of Health and AARP. After 11 years of follow-up, about 13,000 of the men and nearly 6,500 of the women in the study had died of cancer.

A modest inverse association between diabetes and total incident cancer was observed in men (hazard ratio, 0.96), but this stemmed largely from prostate cancer, as expected based on the prior research on diabetes and prostate cancer. In the current study, prostate cancer accounted for 42% of all the cancers in men, and when it was excluded from the analysis, diabetes was found to be positively associated with cancer in men (HR, 1.08) and with cancer mortality in men (HR, 1.20), said Dr. Lai, a cancer prevention fellow at the National Cancer Institute.

Diabetes also was found to have a modest association with cancer in women (HR, 1.06) and with cancer mortality in women (HR, 1.15).

Statistically significant associations were observed for cancers of the colon, rectum, and liver in both men and women (HR, 1.15, 1.28, and 2.40, respectively); for the pancreas and urinary bladder in men (HR, 1.47 and 1.10, respectively); and for the stomach, anus, and corpus and uterus in women (HR, 1.74, 2.44, and 1.20, respectively). The risk estimates for cancers of the pancreas and urinary bladder in women with diabetes were similar to those in men, and the risk estimate for stomach cancer in men was similar to that in women, but these did not reach statistical significance, Dr. Lai said.

No association between diabetes and lung, skin, or other cancers was observed, he noted.

Diabetes in the NIH-AARP study was assessed by self-report in the predominantly white, non-Hispanic cohort, and all analyses included adjustment for age; education; body mass index; smoking status; self-reported health status; physical activity; vitamin supplement use; alcohol intake; diet (fruit, vegetable, and meat consumption); family history of cancer; and – among women – hormonal therapy.

The findings provide additional evidence that abnormal insulin and glucose signaling contribute to cancer risk, and suggest that in addition to myriad other benefits, avoiding diabetes through diet, exercise, and maintenance of healthy body weight potentially reduces the risk for cancer development and mortality, Dr. Lai said.

Further study is needed to elucidate the biologic mechanisms of the association between diabetes and cancer, he concluded.

Dr. Lai said he had no relevant financial disclosures. The study was sponsored by the National Cancer Institute.

ORLANDO – Diabetes appears to be associated with an increased risk of several types of cancer and with an increased risk of cancer-related mortality in both men and women, findings from a large prospective study have shown.

Incidence rates for both diseases are increasing worldwide, and although prior research has demonstrated a decreased risk for prostate cancer in men with diabetes – perhaps due to the lower testosterone levels associated with diabetes – the association between diabetes and other cancers has not been well studied, Gabriel Lai, Ph.D., said at the annual meeting of the American Association for Cancer Research.

To better characterize the association between the two diseases, Dr. Lai and his colleagues analyzed data from the nearly 300,000 men and 200,000 women aged 50-71 years who participated in a diet and health study by the National Institutes of Health and AARP. After 11 years of follow-up, about 13,000 of the men and nearly 6,500 of the women in the study had died of cancer.

A modest inverse association between diabetes and total incident cancer was observed in men (hazard ratio, 0.96), but this stemmed largely from prostate cancer, as expected based on the prior research on diabetes and prostate cancer. In the current study, prostate cancer accounted for 42% of all the cancers in men, and when it was excluded from the analysis, diabetes was found to be positively associated with cancer in men (HR, 1.08) and with cancer mortality in men (HR, 1.20), said Dr. Lai, a cancer prevention fellow at the National Cancer Institute.

Diabetes also was found to have a modest association with cancer in women (HR, 1.06) and with cancer mortality in women (HR, 1.15).

Statistically significant associations were observed for cancers of the colon, rectum, and liver in both men and women (HR, 1.15, 1.28, and 2.40, respectively); for the pancreas and urinary bladder in men (HR, 1.47 and 1.10, respectively); and for the stomach, anus, and corpus and uterus in women (HR, 1.74, 2.44, and 1.20, respectively). The risk estimates for cancers of the pancreas and urinary bladder in women with diabetes were similar to those in men, and the risk estimate for stomach cancer in men was similar to that in women, but these did not reach statistical significance, Dr. Lai said.

No association between diabetes and lung, skin, or other cancers was observed, he noted.

Diabetes in the NIH-AARP study was assessed by self-report in the predominantly white, non-Hispanic cohort, and all analyses included adjustment for age; education; body mass index; smoking status; self-reported health status; physical activity; vitamin supplement use; alcohol intake; diet (fruit, vegetable, and meat consumption); family history of cancer; and – among women – hormonal therapy.

The findings provide additional evidence that abnormal insulin and glucose signaling contribute to cancer risk, and suggest that in addition to myriad other benefits, avoiding diabetes through diet, exercise, and maintenance of healthy body weight potentially reduces the risk for cancer development and mortality, Dr. Lai said.

Further study is needed to elucidate the biologic mechanisms of the association between diabetes and cancer, he concluded.

Dr. Lai said he had no relevant financial disclosures. The study was sponsored by the National Cancer Institute.

ORLANDO – Diabetes appears to be associated with an increased risk of several types of cancer and with an increased risk of cancer-related mortality in both men and women, findings from a large prospective study have shown.

Incidence rates for both diseases are increasing worldwide, and although prior research has demonstrated a decreased risk for prostate cancer in men with diabetes – perhaps due to the lower testosterone levels associated with diabetes – the association between diabetes and other cancers has not been well studied, Gabriel Lai, Ph.D., said at the annual meeting of the American Association for Cancer Research.

To better characterize the association between the two diseases, Dr. Lai and his colleagues analyzed data from the nearly 300,000 men and 200,000 women aged 50-71 years who participated in a diet and health study by the National Institutes of Health and AARP. After 11 years of follow-up, about 13,000 of the men and nearly 6,500 of the women in the study had died of cancer.

A modest inverse association between diabetes and total incident cancer was observed in men (hazard ratio, 0.96), but this stemmed largely from prostate cancer, as expected based on the prior research on diabetes and prostate cancer. In the current study, prostate cancer accounted for 42% of all the cancers in men, and when it was excluded from the analysis, diabetes was found to be positively associated with cancer in men (HR, 1.08) and with cancer mortality in men (HR, 1.20), said Dr. Lai, a cancer prevention fellow at the National Cancer Institute.

Diabetes also was found to have a modest association with cancer in women (HR, 1.06) and with cancer mortality in women (HR, 1.15).

Statistically significant associations were observed for cancers of the colon, rectum, and liver in both men and women (HR, 1.15, 1.28, and 2.40, respectively); for the pancreas and urinary bladder in men (HR, 1.47 and 1.10, respectively); and for the stomach, anus, and corpus and uterus in women (HR, 1.74, 2.44, and 1.20, respectively). The risk estimates for cancers of the pancreas and urinary bladder in women with diabetes were similar to those in men, and the risk estimate for stomach cancer in men was similar to that in women, but these did not reach statistical significance, Dr. Lai said.

No association between diabetes and lung, skin, or other cancers was observed, he noted.

Diabetes in the NIH-AARP study was assessed by self-report in the predominantly white, non-Hispanic cohort, and all analyses included adjustment for age; education; body mass index; smoking status; self-reported health status; physical activity; vitamin supplement use; alcohol intake; diet (fruit, vegetable, and meat consumption); family history of cancer; and – among women – hormonal therapy.

The findings provide additional evidence that abnormal insulin and glucose signaling contribute to cancer risk, and suggest that in addition to myriad other benefits, avoiding diabetes through diet, exercise, and maintenance of healthy body weight potentially reduces the risk for cancer development and mortality, Dr. Lai said.

Further study is needed to elucidate the biologic mechanisms of the association between diabetes and cancer, he concluded.

Dr. Lai said he had no relevant financial disclosures. The study was sponsored by the National Cancer Institute.

ORLANDO – Diabetes appears to be associated with an increased risk of several types of cancer and with an increased risk of cancer-related mortality in both men and women, findings from a large prospective study have shown.

Incidence rates for both diseases are increasing worldwide, and although prior research has demonstrated a decreased risk for prostate cancer in men with diabetes – perhaps due to the lower testosterone levels associated with diabetes – the association between diabetes and other cancers has not been well studied, Gabriel Lai, Ph.D., said at the annual meeting of the American Association for Cancer Research.

To better characterize the association between the two diseases, Dr. Lai and his colleagues analyzed data from the nearly 300,000 men and 200,000 women aged 50-71 years who participated in a diet and health study by the National Institutes of Health and AARP. After 11 years of follow-up, about 13,000 of the men and nearly 6,500 of the women in the study had died of cancer.

A modest inverse association between diabetes and total incident cancer was observed in men (hazard ratio, 0.96), but this stemmed largely from prostate cancer, as expected based on the prior research on diabetes and prostate cancer. In the current study, prostate cancer accounted for 42% of all the cancers in men, and when it was excluded from the analysis, diabetes was found to be positively associated with cancer in men (HR, 1.08) and with cancer mortality in men (HR, 1.20), said Dr. Lai, a cancer prevention fellow at the National Cancer Institute.

Diabetes also was found to have a modest association with cancer in women (HR, 1.06) and with cancer mortality in women (HR, 1.15).

Statistically significant associations were observed for cancers of the colon, rectum, and liver in both men and women (HR, 1.15, 1.28, and 2.40, respectively); for the pancreas and urinary bladder in men (HR, 1.47 and 1.10, respectively); and for the stomach, anus, and corpus and uterus in women (HR, 1.74, 2.44, and 1.20, respectively). The risk estimates for cancers of the pancreas and urinary bladder in women with diabetes were similar to those in men, and the risk estimate for stomach cancer in men was similar to that in women, but these did not reach statistical significance, Dr. Lai said.

No association between diabetes and lung, skin, or other cancers was observed, he noted.

Diabetes in the NIH-AARP study was assessed by self-report in the predominantly white, non-Hispanic cohort, and all analyses included adjustment for age; education; body mass index; smoking status; self-reported health status; physical activity; vitamin supplement use; alcohol intake; diet (fruit, vegetable, and meat consumption); family history of cancer; and – among women – hormonal therapy.

The findings provide additional evidence that abnormal insulin and glucose signaling contribute to cancer risk, and suggest that in addition to myriad other benefits, avoiding diabetes through diet, exercise, and maintenance of healthy body weight potentially reduces the risk for cancer development and mortality, Dr. Lai said.

Further study is needed to elucidate the biologic mechanisms of the association between diabetes and cancer, he concluded.

Dr. Lai said he had no relevant financial disclosures. The study was sponsored by the National Cancer Institute.

ORLANDO – Diabetes appears to be associated with an increased risk of several types of cancer and with an increased risk of cancer-related mortality in both men and women, findings from a large prospective study have shown.

Incidence rates for both diseases are increasing worldwide, and although prior research has demonstrated a decreased risk for prostate cancer in men with diabetes – perhaps due to the lower testosterone levels associated with diabetes – the association between diabetes and other cancers has not been well studied, Gabriel Lai, Ph.D., said at the annual meeting of the American Association for Cancer Research.

To better characterize the association between the two diseases, Dr. Lai and his colleagues analyzed data from the nearly 300,000 men and 200,000 women aged 50-71 years who participated in a diet and health study by the National Institutes of Health and AARP. After 11 years of follow-up, about 13,000 of the men and nearly 6,500 of the women in the study had died of cancer.

A modest inverse association between diabetes and total incident cancer was observed in men (hazard ratio, 0.96), but this stemmed largely from prostate cancer, as expected based on the prior research on diabetes and prostate cancer. In the current study, prostate cancer accounted for 42% of all the cancers in men, and when it was excluded from the analysis, diabetes was found to be positively associated with cancer in men (HR, 1.08) and with cancer mortality in men (HR, 1.20), said Dr. Lai, a cancer prevention fellow at the National Cancer Institute.

Diabetes also was found to have a modest association with cancer in women (HR, 1.06) and with cancer mortality in women (HR, 1.15).

Statistically significant associations were observed for cancers of the colon, rectum, and liver in both men and women (HR, 1.15, 1.28, and 2.40, respectively); for the pancreas and urinary bladder in men (HR, 1.47 and 1.10, respectively); and for the stomach, anus, and corpus and uterus in women (HR, 1.74, 2.44, and 1.20, respectively). The risk estimates for cancers of the pancreas and urinary bladder in women with diabetes were similar to those in men, and the risk estimate for stomach cancer in men was similar to that in women, but these did not reach statistical significance, Dr. Lai said.

No association between diabetes and lung, skin, or other cancers was observed, he noted.

Diabetes in the NIH-AARP study was assessed by self-report in the predominantly white, non-Hispanic cohort, and all analyses included adjustment for age; education; body mass index; smoking status; self-reported health status; physical activity; vitamin supplement use; alcohol intake; diet (fruit, vegetable, and meat consumption); family history of cancer; and – among women – hormonal therapy.

The findings provide additional evidence that abnormal insulin and glucose signaling contribute to cancer risk, and suggest that in addition to myriad other benefits, avoiding diabetes through diet, exercise, and maintenance of healthy body weight potentially reduces the risk for cancer development and mortality, Dr. Lai said.

Further study is needed to elucidate the biologic mechanisms of the association between diabetes and cancer, he concluded.

Dr. Lai said he had no relevant financial disclosures. The study was sponsored by the National Cancer Institute.

ORLANDO – Diabetes appears to be associated with an increased risk of several types of cancer and with an increased risk of cancer-related mortality in both men and women, findings from a large prospective study have shown.

Incidence rates for both diseases are increasing worldwide, and although prior research has demonstrated a decreased risk for prostate cancer in men with diabetes – perhaps due to the lower testosterone levels associated with diabetes – the association between diabetes and other cancers has not been well studied, Gabriel Lai, Ph.D., said at the annual meeting of the American Association for Cancer Research.

To better characterize the association between the two diseases, Dr. Lai and his colleagues analyzed data from the nearly 300,000 men and 200,000 women aged 50-71 years who participated in a diet and health study by the National Institutes of Health and AARP. After 11 years of follow-up, about 13,000 of the men and nearly 6,500 of the women in the study had died of cancer.

A modest inverse association between diabetes and total incident cancer was observed in men (hazard ratio, 0.96), but this stemmed largely from prostate cancer, as expected based on the prior research on diabetes and prostate cancer. In the current study, prostate cancer accounted for 42% of all the cancers in men, and when it was excluded from the analysis, diabetes was found to be positively associated with cancer in men (HR, 1.08) and with cancer mortality in men (HR, 1.20), said Dr. Lai, a cancer prevention fellow at the National Cancer Institute.

Diabetes also was found to have a modest association with cancer in women (HR, 1.06) and with cancer mortality in women (HR, 1.15).

Statistically significant associations were observed for cancers of the colon, rectum, and liver in both men and women (HR, 1.15, 1.28, and 2.40, respectively); for the pancreas and urinary bladder in men (HR, 1.47 and 1.10, respectively); and for the stomach, anus, and corpus and uterus in women (HR, 1.74, 2.44, and 1.20, respectively). The risk estimates for cancers of the pancreas and urinary bladder in women with diabetes were similar to those in men, and the risk estimate for stomach cancer in men was similar to that in women, but these did not reach statistical significance, Dr. Lai said.

No association between diabetes and lung, skin, or other cancers was observed, he noted.

Diabetes in the NIH-AARP study was assessed by self-report in the predominantly white, non-Hispanic cohort, and all analyses included adjustment for age; education; body mass index; smoking status; self-reported health status; physical activity; vitamin supplement use; alcohol intake; diet (fruit, vegetable, and meat consumption); family history of cancer; and – among women – hormonal therapy.

The findings provide additional evidence that abnormal insulin and glucose signaling contribute to cancer risk, and suggest that in addition to myriad other benefits, avoiding diabetes through diet, exercise, and maintenance of healthy body weight potentially reduces the risk for cancer development and mortality, Dr. Lai said.

Further study is needed to elucidate the biologic mechanisms of the association between diabetes and cancer, he concluded.

Dr. Lai said he had no relevant financial disclosures. The study was sponsored by the National Cancer Institute.

ORLANDO – Massively parallel sequencing of DNA from tumor samples in 50 patients with luminal-type breast cancer revealed a novel mutation in the breast cancer tumor suppressor gene MAP3K1, which normally controls programmed cell death.

Presumably, the knockout mutation – which affected about 10% of estrogen receptor–positive breast cancers in the study and which "unequivocally destroys the function of the gene" – allows cells to survive when they would normally die, Dr. Matthew J. Ellis said at the annual meeting of the American Association for Cancer Research.

This finding, along with others from the sequencing of more than 10 trillion chemical bases of DNA in this extensive genomics investigation (one of the largest to date), marks an important early step toward personalized therapy for breast cancer patients who fail to respond to estrogen-lowering therapy prior to surgery, said Dr. Ellis, professor of medicine and chief of breast oncology at the Washington University in St. Louis.

Luminal-type breast cancer is the most common form of the disease, accounting for 70%-80% of hormone receptor–positive breast cancers. Many patients have a good prognosis, but a subset has this very aggressive type of disease. Indeed, more patients die of aggressive luminal-type breast cancer than do all other breast cancer subtypes combined, he said.

"So we set out to find a molecular basis for poor outcome in receptor-positive disease," he said.

DNA from tumor samples of patients who were enrolled in ongoing neoadjuvant endocrine clinical trials – 24 of whom were resistant to estrogen receptor–targeted therapy – was used for the supercomputer-conducted analysis. The whole genomes of the tumors were compared with the matched DNA of the same patients’ healthy cells, allowing identification of mutations occurring only in the cancer cells.

In all, 1,700 mutations were identified, and most of these were unique to individuals. In addition to two previously identified, relatively common mutations (PIK3CA and TP53), Dr. Ellis and his colleagues found only three others – including MAP3K1 – that recurred at a frequency of at least 10%; the other two were ATR and MYST3.

PIK3CA and TP53 were the most frequently mutated genes in estrogen receptor–positive breast cancer in this study, occurring in about 50% and 20% of tumors, respectively. MAP3K1 was the third most commonly mutated gene.

Considering the large number of mutations found, it was "a rather shocking result" to find only three new gene mutations at the 10% recurrence level, Dr. Ellis said. "What it says is that breast cancer is highly complex, that the genetic make-up involves a large number of mutations that averages about 20 tier-1 [or coding region] mutations in each tumor, and there’s a wide range," he added.

But the findings do offer a glimpse into how therapy can be personalized.

Using a "very, very simple model" produced by this analysis, Dr. Ellis illustrated how a constellation of mutations could be used to predict response or resistance patterns: The three-gene cluster of mutated MAP3K1, mutated PIK3CA, and wild type TP53, which occurred in a small subset of patients, was shown to be significantly associated with "luminal A status [indicative of good prognosis], suppressed proliferation, and favorable small tumors at the end of neoadjuvant treatment," he said.

Although there remains "a great sea of unknown," the findings – when considered in the context of the growing list of "druggable mutations" and treatments approved for other diseases – allow for a vision of therapy that involves obtaining the genetic information in advance of treatment to allow for the design of individually appropriate therapy to address the problem of resistance.

"Very clearly, this is a big problem clinically ... and only a tailored approach will lead to a solution to the problem," he said.

Dr. Ellis disclosed that he has received grant or research support from and/or served on the speakers bureau for Novartis, AstraZeneca, and Bioclassifier LLC.

ORLANDO – Massively parallel sequencing of DNA from tumor samples in 50 patients with luminal-type breast cancer revealed a novel mutation in the breast cancer tumor suppressor gene MAP3K1, which normally controls programmed cell death.

Presumably, the knockout mutation – which affected about 10% of estrogen receptor–positive breast cancers in the study and which "unequivocally destroys the function of the gene" – allows cells to survive when they would normally die, Dr. Matthew J. Ellis said at the annual meeting of the American Association for Cancer Research.

This finding, along with others from the sequencing of more than 10 trillion chemical bases of DNA in this extensive genomics investigation (one of the largest to date), marks an important early step toward personalized therapy for breast cancer patients who fail to respond to estrogen-lowering therapy prior to surgery, said Dr. Ellis, professor of medicine and chief of breast oncology at the Washington University in St. Louis.

Luminal-type breast cancer is the most common form of the disease, accounting for 70%-80% of hormone receptor–positive breast cancers. Many patients have a good prognosis, but a subset has this very aggressive type of disease. Indeed, more patients die of aggressive luminal-type breast cancer than do all other breast cancer subtypes combined, he said.

"So we set out to find a molecular basis for poor outcome in receptor-positive disease," he said.

DNA from tumor samples of patients who were enrolled in ongoing neoadjuvant endocrine clinical trials – 24 of whom were resistant to estrogen receptor–targeted therapy – was used for the supercomputer-conducted analysis. The whole genomes of the tumors were compared with the matched DNA of the same patients’ healthy cells, allowing identification of mutations occurring only in the cancer cells.

In all, 1,700 mutations were identified, and most of these were unique to individuals. In addition to two previously identified, relatively common mutations (PIK3CA and TP53), Dr. Ellis and his colleagues found only three others – including MAP3K1 – that recurred at a frequency of at least 10%; the other two were ATR and MYST3.

PIK3CA and TP53 were the most frequently mutated genes in estrogen receptor–positive breast cancer in this study, occurring in about 50% and 20% of tumors, respectively. MAP3K1 was the third most commonly mutated gene.

Considering the large number of mutations found, it was "a rather shocking result" to find only three new gene mutations at the 10% recurrence level, Dr. Ellis said. "What it says is that breast cancer is highly complex, that the genetic make-up involves a large number of mutations that averages about 20 tier-1 [or coding region] mutations in each tumor, and there’s a wide range," he added.

But the findings do offer a glimpse into how therapy can be personalized.

Using a "very, very simple model" produced by this analysis, Dr. Ellis illustrated how a constellation of mutations could be used to predict response or resistance patterns: The three-gene cluster of mutated MAP3K1, mutated PIK3CA, and wild type TP53, which occurred in a small subset of patients, was shown to be significantly associated with "luminal A status [indicative of good prognosis], suppressed proliferation, and favorable small tumors at the end of neoadjuvant treatment," he said.

Although there remains "a great sea of unknown," the findings – when considered in the context of the growing list of "druggable mutations" and treatments approved for other diseases – allow for a vision of therapy that involves obtaining the genetic information in advance of treatment to allow for the design of individually appropriate therapy to address the problem of resistance.

"Very clearly, this is a big problem clinically ... and only a tailored approach will lead to a solution to the problem," he said.

Dr. Ellis disclosed that he has received grant or research support from and/or served on the speakers bureau for Novartis, AstraZeneca, and Bioclassifier LLC.

ORLANDO – Massively parallel sequencing of DNA from tumor samples in 50 patients with luminal-type breast cancer revealed a novel mutation in the breast cancer tumor suppressor gene MAP3K1, which normally controls programmed cell death.

Presumably, the knockout mutation – which affected about 10% of estrogen receptor–positive breast cancers in the study and which "unequivocally destroys the function of the gene" – allows cells to survive when they would normally die, Dr. Matthew J. Ellis said at the annual meeting of the American Association for Cancer Research.

This finding, along with others from the sequencing of more than 10 trillion chemical bases of DNA in this extensive genomics investigation (one of the largest to date), marks an important early step toward personalized therapy for breast cancer patients who fail to respond to estrogen-lowering therapy prior to surgery, said Dr. Ellis, professor of medicine and chief of breast oncology at the Washington University in St. Louis.

Luminal-type breast cancer is the most common form of the disease, accounting for 70%-80% of hormone receptor–positive breast cancers. Many patients have a good prognosis, but a subset has this very aggressive type of disease. Indeed, more patients die of aggressive luminal-type breast cancer than do all other breast cancer subtypes combined, he said.

"So we set out to find a molecular basis for poor outcome in receptor-positive disease," he said.

DNA from tumor samples of patients who were enrolled in ongoing neoadjuvant endocrine clinical trials – 24 of whom were resistant to estrogen receptor–targeted therapy – was used for the supercomputer-conducted analysis. The whole genomes of the tumors were compared with the matched DNA of the same patients’ healthy cells, allowing identification of mutations occurring only in the cancer cells.

In all, 1,700 mutations were identified, and most of these were unique to individuals. In addition to two previously identified, relatively common mutations (PIK3CA and TP53), Dr. Ellis and his colleagues found only three others – including MAP3K1 – that recurred at a frequency of at least 10%; the other two were ATR and MYST3.

PIK3CA and TP53 were the most frequently mutated genes in estrogen receptor–positive breast cancer in this study, occurring in about 50% and 20% of tumors, respectively. MAP3K1 was the third most commonly mutated gene.

Considering the large number of mutations found, it was "a rather shocking result" to find only three new gene mutations at the 10% recurrence level, Dr. Ellis said. "What it says is that breast cancer is highly complex, that the genetic make-up involves a large number of mutations that averages about 20 tier-1 [or coding region] mutations in each tumor, and there’s a wide range," he added.

But the findings do offer a glimpse into how therapy can be personalized.

Using a "very, very simple model" produced by this analysis, Dr. Ellis illustrated how a constellation of mutations could be used to predict response or resistance patterns: The three-gene cluster of mutated MAP3K1, mutated PIK3CA, and wild type TP53, which occurred in a small subset of patients, was shown to be significantly associated with "luminal A status [indicative of good prognosis], suppressed proliferation, and favorable small tumors at the end of neoadjuvant treatment," he said.

Although there remains "a great sea of unknown," the findings – when considered in the context of the growing list of "druggable mutations" and treatments approved for other diseases – allow for a vision of therapy that involves obtaining the genetic information in advance of treatment to allow for the design of individually appropriate therapy to address the problem of resistance.

"Very clearly, this is a big problem clinically ... and only a tailored approach will lead to a solution to the problem," he said.

Dr. Ellis disclosed that he has received grant or research support from and/or served on the speakers bureau for Novartis, AstraZeneca, and Bioclassifier LLC.

ORLANDO – People with AIDS have a substantially increased risk of developing stomach and esophageal malignancies, compared with the general public, according to an analysis of data from the large, population-based HIV/AIDS Cancer Match Study.

Among the more than 600,000 people with AIDS who were included in the analysis, 1,166 developed stomach malignancies and 240 developed esophageal malignancies. The overall risks of stomach and esophageal malignancies were 6.9-fold and 2.7-fold higher, respectively, than in the general population, E. Christina Persson, Ph.D., reported at the annual meeting of the American Association for Cancer Research.

Although most of the increased risk was attributable to lymphomas, the risk of carcinomas was also increased. The lymphomas were not surprising, as AIDS patients are known to be at increased risk for these cancers, but the greater risk for carcinomas is a new finding, Dr. Persson said.

People with AIDS who were included in the HIV/AIDS Cancer Match Study (a linkage of 15 U.S. population–based HIV/AIDS and cancer registries) were registered in 1980-2007. This population is known to have a higher prevalence of cancer risk factors, as well an increased risk of infection-related malignancies resulting from a suppressed immune system. As AIDS therapies – and thus, survival - have improved, concern regarding cancer risk is increased.

In the current study, the risk of stomach carcinomas was increased 70% (standardized incidence ratio, 1.7), whereas the risk of stomach lymphomas was 36-fold higher. Similar increases in risk were seen for proximal (cardia) and distal (noncardia) carcinomas (SIR, 1.5 and 1.8, respectively), said Dr. Persson, a postdoctoral fellow at the National Cancer Institute.

The risk for esophageal carcinomas was increased 80% (SIR, 1.8), with a 54% increased risk of squamous cell carcinomas and a 101% increased risk for adenocarcinomas (SIR, 1.5 and 2.0), whereas there was a 261-fold increased risk of esophageal lymphomas, she said.

Dr. Judy E. Garber, the new AACR president and moderator of the press briefing where Dr. Persson discussed her findings, said the report is both fascinating and worrisome.

Given that most AIDS-related cancers are lymphomas, it is "quite remarkable to show solid tumor differences" in the AIDS population vs. the general public, she said, adding that she hopes this is not an indication that people who are surviving AIDS thanks to better treatments will have other problems, such as increased cancer risks, to contend with.

Although the findings do not warrant routine screening for solid tumors in the AIDS population at this time, this increased risk is something for clinicians to keep in mind when they care for AIDS survivors, said Dr. Garber, director of the center for cancer genetics and prevention at the Dana-Farber Cancer Institute, Boston.

Dr. Persson had no disclosures.

ORLANDO – People with AIDS have a substantially increased risk of developing stomach and esophageal malignancies, compared with the general public, according to an analysis of data from the large, population-based HIV/AIDS Cancer Match Study.

Among the more than 600,000 people with AIDS who were included in the analysis, 1,166 developed stomach malignancies and 240 developed esophageal malignancies. The overall risks of stomach and esophageal malignancies were 6.9-fold and 2.7-fold higher, respectively, than in the general population, E. Christina Persson, Ph.D., reported at the annual meeting of the American Association for Cancer Research.

Although most of the increased risk was attributable to lymphomas, the risk of carcinomas was also increased. The lymphomas were not surprising, as AIDS patients are known to be at increased risk for these cancers, but the greater risk for carcinomas is a new finding, Dr. Persson said.

People with AIDS who were included in the HIV/AIDS Cancer Match Study (a linkage of 15 U.S. population–based HIV/AIDS and cancer registries) were registered in 1980-2007. This population is known to have a higher prevalence of cancer risk factors, as well an increased risk of infection-related malignancies resulting from a suppressed immune system. As AIDS therapies – and thus, survival - have improved, concern regarding cancer risk is increased.

In the current study, the risk of stomach carcinomas was increased 70% (standardized incidence ratio, 1.7), whereas the risk of stomach lymphomas was 36-fold higher. Similar increases in risk were seen for proximal (cardia) and distal (noncardia) carcinomas (SIR, 1.5 and 1.8, respectively), said Dr. Persson, a postdoctoral fellow at the National Cancer Institute.

The risk for esophageal carcinomas was increased 80% (SIR, 1.8), with a 54% increased risk of squamous cell carcinomas and a 101% increased risk for adenocarcinomas (SIR, 1.5 and 2.0), whereas there was a 261-fold increased risk of esophageal lymphomas, she said.

Dr. Judy E. Garber, the new AACR president and moderator of the press briefing where Dr. Persson discussed her findings, said the report is both fascinating and worrisome.

Given that most AIDS-related cancers are lymphomas, it is "quite remarkable to show solid tumor differences" in the AIDS population vs. the general public, she said, adding that she hopes this is not an indication that people who are surviving AIDS thanks to better treatments will have other problems, such as increased cancer risks, to contend with.

Although the findings do not warrant routine screening for solid tumors in the AIDS population at this time, this increased risk is something for clinicians to keep in mind when they care for AIDS survivors, said Dr. Garber, director of the center for cancer genetics and prevention at the Dana-Farber Cancer Institute, Boston.

Dr. Persson had no disclosures.

ORLANDO – People with AIDS have a substantially increased risk of developing stomach and esophageal malignancies, compared with the general public, according to an analysis of data from the large, population-based HIV/AIDS Cancer Match Study.

Among the more than 600,000 people with AIDS who were included in the analysis, 1,166 developed stomach malignancies and 240 developed esophageal malignancies. The overall risks of stomach and esophageal malignancies were 6.9-fold and 2.7-fold higher, respectively, than in the general population, E. Christina Persson, Ph.D., reported at the annual meeting of the American Association for Cancer Research.

Although most of the increased risk was attributable to lymphomas, the risk of carcinomas was also increased. The lymphomas were not surprising, as AIDS patients are known to be at increased risk for these cancers, but the greater risk for carcinomas is a new finding, Dr. Persson said.

People with AIDS who were included in the HIV/AIDS Cancer Match Study (a linkage of 15 U.S. population–based HIV/AIDS and cancer registries) were registered in 1980-2007. This population is known to have a higher prevalence of cancer risk factors, as well an increased risk of infection-related malignancies resulting from a suppressed immune system. As AIDS therapies – and thus, survival - have improved, concern regarding cancer risk is increased.

In the current study, the risk of stomach carcinomas was increased 70% (standardized incidence ratio, 1.7), whereas the risk of stomach lymphomas was 36-fold higher. Similar increases in risk were seen for proximal (cardia) and distal (noncardia) carcinomas (SIR, 1.5 and 1.8, respectively), said Dr. Persson, a postdoctoral fellow at the National Cancer Institute.

The risk for esophageal carcinomas was increased 80% (SIR, 1.8), with a 54% increased risk of squamous cell carcinomas and a 101% increased risk for adenocarcinomas (SIR, 1.5 and 2.0), whereas there was a 261-fold increased risk of esophageal lymphomas, she said.

Dr. Judy E. Garber, the new AACR president and moderator of the press briefing where Dr. Persson discussed her findings, said the report is both fascinating and worrisome.

Given that most AIDS-related cancers are lymphomas, it is "quite remarkable to show solid tumor differences" in the AIDS population vs. the general public, she said, adding that she hopes this is not an indication that people who are surviving AIDS thanks to better treatments will have other problems, such as increased cancer risks, to contend with.

Although the findings do not warrant routine screening for solid tumors in the AIDS population at this time, this increased risk is something for clinicians to keep in mind when they care for AIDS survivors, said Dr. Garber, director of the center for cancer genetics and prevention at the Dana-Farber Cancer Institute, Boston.

Dr. Persson had no disclosures.

ORLANDO – People with AIDS have a substantially increased risk of developing stomach and esophageal malignancies, compared with the general public, according to an analysis of data from the large, population-based HIV/AIDS Cancer Match Study.

Among the more than 600,000 people with AIDS who were included in the analysis, 1,166 developed stomach malignancies and 240 developed esophageal malignancies. The overall risks of stomach and esophageal malignancies were 6.9-fold and 2.7-fold higher, respectively, than in the general population, E. Christina Persson, Ph.D., reported at the annual meeting of the American Association for Cancer Research.

Although most of the increased risk was attributable to lymphomas, the risk of carcinomas was also increased. The lymphomas were not surprising, as AIDS patients are known to be at increased risk for these cancers, but the greater risk for carcinomas is a new finding, Dr. Persson said.

People with AIDS who were included in the HIV/AIDS Cancer Match Study (a linkage of 15 U.S. population–based HIV/AIDS and cancer registries) were registered in 1980-2007. This population is known to have a higher prevalence of cancer risk factors, as well an increased risk of infection-related malignancies resulting from a suppressed immune system. As AIDS therapies – and thus, survival - have improved, concern regarding cancer risk is increased.

In the current study, the risk of stomach carcinomas was increased 70% (standardized incidence ratio, 1.7), whereas the risk of stomach lymphomas was 36-fold higher. Similar increases in risk were seen for proximal (cardia) and distal (noncardia) carcinomas (SIR, 1.5 and 1.8, respectively), said Dr. Persson, a postdoctoral fellow at the National Cancer Institute.

The risk for esophageal carcinomas was increased 80% (SIR, 1.8), with a 54% increased risk of squamous cell carcinomas and a 101% increased risk for adenocarcinomas (SIR, 1.5 and 2.0), whereas there was a 261-fold increased risk of esophageal lymphomas, she said.

Dr. Judy E. Garber, the new AACR president and moderator of the press briefing where Dr. Persson discussed her findings, said the report is both fascinating and worrisome.

Given that most AIDS-related cancers are lymphomas, it is "quite remarkable to show solid tumor differences" in the AIDS population vs. the general public, she said, adding that she hopes this is not an indication that people who are surviving AIDS thanks to better treatments will have other problems, such as increased cancer risks, to contend with.

Although the findings do not warrant routine screening for solid tumors in the AIDS population at this time, this increased risk is something for clinicians to keep in mind when they care for AIDS survivors, said Dr. Garber, director of the center for cancer genetics and prevention at the Dana-Farber Cancer Institute, Boston.

Dr. Persson had no disclosures.

ORLANDO – People with AIDS have a substantially increased risk of developing stomach and esophageal malignancies, compared with the general public, according to an analysis of data from the large, population-based HIV/AIDS Cancer Match Study.

Among the more than 600,000 people with AIDS who were included in the analysis, 1,166 developed stomach malignancies and 240 developed esophageal malignancies. The overall risks of stomach and esophageal malignancies were 6.9-fold and 2.7-fold higher, respectively, than in the general population, E. Christina Persson, Ph.D., reported at the annual meeting of the American Association for Cancer Research.

Although most of the increased risk was attributable to lymphomas, the risk of carcinomas was also increased. The lymphomas were not surprising, as AIDS patients are known to be at increased risk for these cancers, but the greater risk for carcinomas is a new finding, Dr. Persson said.

People with AIDS who were included in the HIV/AIDS Cancer Match Study (a linkage of 15 U.S. population–based HIV/AIDS and cancer registries) were registered in 1980-2007. This population is known to have a higher prevalence of cancer risk factors, as well an increased risk of infection-related malignancies resulting from a suppressed immune system. As AIDS therapies – and thus, survival - have improved, concern regarding cancer risk is increased.

In the current study, the risk of stomach carcinomas was increased 70% (standardized incidence ratio, 1.7), whereas the risk of stomach lymphomas was 36-fold higher. Similar increases in risk were seen for proximal (cardia) and distal (noncardia) carcinomas (SIR, 1.5 and 1.8, respectively), said Dr. Persson, a postdoctoral fellow at the National Cancer Institute.

The risk for esophageal carcinomas was increased 80% (SIR, 1.8), with a 54% increased risk of squamous cell carcinomas and a 101% increased risk for adenocarcinomas (SIR, 1.5 and 2.0), whereas there was a 261-fold increased risk of esophageal lymphomas, she said.

Dr. Judy E. Garber, the new AACR president and moderator of the press briefing where Dr. Persson discussed her findings, said the report is both fascinating and worrisome.

Given that most AIDS-related cancers are lymphomas, it is "quite remarkable to show solid tumor differences" in the AIDS population vs. the general public, she said, adding that she hopes this is not an indication that people who are surviving AIDS thanks to better treatments will have other problems, such as increased cancer risks, to contend with.

Although the findings do not warrant routine screening for solid tumors in the AIDS population at this time, this increased risk is something for clinicians to keep in mind when they care for AIDS survivors, said Dr. Garber, director of the center for cancer genetics and prevention at the Dana-Farber Cancer Institute, Boston.

Dr. Persson had no disclosures.

ORLANDO – People with AIDS have a substantially increased risk of developing stomach and esophageal malignancies, compared with the general public, according to an analysis of data from the large, population-based HIV/AIDS Cancer Match Study.

Among the more than 600,000 people with AIDS who were included in the analysis, 1,166 developed stomach malignancies and 240 developed esophageal malignancies. The overall risks of stomach and esophageal malignancies were 6.9-fold and 2.7-fold higher, respectively, than in the general population, E. Christina Persson, Ph.D., reported at the annual meeting of the American Association for Cancer Research.

Although most of the increased risk was attributable to lymphomas, the risk of carcinomas was also increased. The lymphomas were not surprising, as AIDS patients are known to be at increased risk for these cancers, but the greater risk for carcinomas is a new finding, Dr. Persson said.

People with AIDS who were included in the HIV/AIDS Cancer Match Study (a linkage of 15 U.S. population–based HIV/AIDS and cancer registries) were registered in 1980-2007. This population is known to have a higher prevalence of cancer risk factors, as well an increased risk of infection-related malignancies resulting from a suppressed immune system. As AIDS therapies – and thus, survival - have improved, concern regarding cancer risk is increased.

In the current study, the risk of stomach carcinomas was increased 70% (standardized incidence ratio, 1.7), whereas the risk of stomach lymphomas was 36-fold higher. Similar increases in risk were seen for proximal (cardia) and distal (noncardia) carcinomas (SIR, 1.5 and 1.8, respectively), said Dr. Persson, a postdoctoral fellow at the National Cancer Institute.

The risk for esophageal carcinomas was increased 80% (SIR, 1.8), with a 54% increased risk of squamous cell carcinomas and a 101% increased risk for adenocarcinomas (SIR, 1.5 and 2.0), whereas there was a 261-fold increased risk of esophageal lymphomas, she said.

Dr. Judy E. Garber, the new AACR president and moderator of the press briefing where Dr. Persson discussed her findings, said the report is both fascinating and worrisome.

Given that most AIDS-related cancers are lymphomas, it is "quite remarkable to show solid tumor differences" in the AIDS population vs. the general public, she said, adding that she hopes this is not an indication that people who are surviving AIDS thanks to better treatments will have other problems, such as increased cancer risks, to contend with.

Although the findings do not warrant routine screening for solid tumors in the AIDS population at this time, this increased risk is something for clinicians to keep in mind when they care for AIDS survivors, said Dr. Garber, director of the center for cancer genetics and prevention at the Dana-Farber Cancer Institute, Boston.

Dr. Persson had no disclosures.

ORLANDO - Ovarian cancer patients with BRCA1 or BRCA2 gene mutations have better survival than do those with neither mutation, and those with the BRCA2 mutation have better survival than do those with the BRCA1 mutation, according to the findings of a large, multicenter study.

The findings confirm the results of several prior smaller studies showing a survival advantage in mutation carriers vs. nonmutation carriers, and they provide the first direct evidence that BRCA1 and BRCA2 mutations have differing effects on survival, Kelly L. Bolton reported at the annual meeting of the American Association for Cancer Research.

She and her colleagues studied 3,531 women with invasive epithelial ovarian cancer who were enrolled in one of 24 studies in the United States, Europe, Israel, and Asia, and for whom survival data were available. They excluded patients who either were known or were likely not to have received platinum-based therapy. Included were 1,178 women with BRCA1, 367 with BRCA2, and 1,986 who were BRCA negative.

The 5-year survival was 36% in those with no mutation, 46% of those with the BRCA1 mutation, and 61% of those with the BRCA2 mutation, after adjustment for stage, grade, histology, and age at diagnosis, said Ms. Bolton, a predoctoral fellow at the National Cancer Institute.

The difference in survival between the BRCA1 mutation carriers and those with no mutation was modest, although not statistically significant (hazard ratio, 0.84). However, the difference between the BRCA2 mutation carriers and both the noncarriers and the BRCA1 mutation carriers (after adjustment for age at diagnosis) did reach statistical significance (HR, 0.57 and 0.69, respectively).

Even after the exclusion of all but high-grade, advanced-stage serous cases, the survival differences persisted, Ms. Bolton reported.

A possible explanation for the differences, based on in vitro work and some retrospective trials, may lie in patients’ responses to chemotherapy; those with the BRCA2 mutation may have an improved response, but unidentified biological differences among BRCA1 carriers, BRCA2 carriers, and noncarriers could also be driving the association, she said.

The BRCA1 and BRCA2 mutation carriers in this study did not differ in regard to tumor stage, grade, or histology. Compared with noncarriers, however, BRCA1 carriers were younger and BRCA2 carriers were older at diagnosis.

Furthermore, compared with noncarriers, BRCA1 and BRCA2 carriers were more likely to present with advanced-stage disease, high-grade disease, and serous disease.

"The findings don’t have any immediate impact on clinical practice, but they do have important implications [for both] clinical prediction and also trial design, particularly for clinical trials," Ms. Bolton said, noting that although germline mutations in the BRCA1 and BRCA2 genes (which are important in DNA damage repair and have distinct yet complementary functions) are rare in the general population, they are present in 10%-15% of those with ovarian cancer.

Indeed, the findings – which "may be a very faint silver lining" for mutation carriers with a terrible disease that still has terrible survival – do speak to the possibility that women with these mutations need to be identified in the setting of ovarian cancer, as the presence of mutations will affect thinking about treatment, said Dr. Judy E. Garber, the new AACR president and director of the center for cancer genetics and prevention at the Dana-Farber Cancer Institute, Boston. Dr. Garber moderated a press briefing where Ms. Bolton discussed her findings,

Ms. Bolton had no relevant disclosures.

ORLANDO - Ovarian cancer patients with BRCA1 or BRCA2 gene mutations have better survival than do those with neither mutation, and those with the BRCA2 mutation have better survival than do those with the BRCA1 mutation, according to the findings of a large, multicenter study.

The findings confirm the results of several prior smaller studies showing a survival advantage in mutation carriers vs. nonmutation carriers, and they provide the first direct evidence that BRCA1 and BRCA2 mutations have differing effects on survival, Kelly L. Bolton reported at the annual meeting of the American Association for Cancer Research.

She and her colleagues studied 3,531 women with invasive epithelial ovarian cancer who were enrolled in one of 24 studies in the United States, Europe, Israel, and Asia, and for whom survival data were available. They excluded patients who either were known or were likely not to have received platinum-based therapy. Included were 1,178 women with BRCA1, 367 with BRCA2, and 1,986 who were BRCA negative.

The 5-year survival was 36% in those with no mutation, 46% of those with the BRCA1 mutation, and 61% of those with the BRCA2 mutation, after adjustment for stage, grade, histology, and age at diagnosis, said Ms. Bolton, a predoctoral fellow at the National Cancer Institute.

The difference in survival between the BRCA1 mutation carriers and those with no mutation was modest, although not statistically significant (hazard ratio, 0.84). However, the difference between the BRCA2 mutation carriers and both the noncarriers and the BRCA1 mutation carriers (after adjustment for age at diagnosis) did reach statistical significance (HR, 0.57 and 0.69, respectively).

Even after the exclusion of all but high-grade, advanced-stage serous cases, the survival differences persisted, Ms. Bolton reported.

A possible explanation for the differences, based on in vitro work and some retrospective trials, may lie in patients’ responses to chemotherapy; those with the BRCA2 mutation may have an improved response, but unidentified biological differences among BRCA1 carriers, BRCA2 carriers, and noncarriers could also be driving the association, she said.

The BRCA1 and BRCA2 mutation carriers in this study did not differ in regard to tumor stage, grade, or histology. Compared with noncarriers, however, BRCA1 carriers were younger and BRCA2 carriers were older at diagnosis.

Furthermore, compared with noncarriers, BRCA1 and BRCA2 carriers were more likely to present with advanced-stage disease, high-grade disease, and serous disease.

"The findings don’t have any immediate impact on clinical practice, but they do have important implications [for both] clinical prediction and also trial design, particularly for clinical trials," Ms. Bolton said, noting that although germline mutations in the BRCA1 and BRCA2 genes (which are important in DNA damage repair and have distinct yet complementary functions) are rare in the general population, they are present in 10%-15% of those with ovarian cancer.

Indeed, the findings – which "may be a very faint silver lining" for mutation carriers with a terrible disease that still has terrible survival – do speak to the possibility that women with these mutations need to be identified in the setting of ovarian cancer, as the presence of mutations will affect thinking about treatment, said Dr. Judy E. Garber, the new AACR president and director of the center for cancer genetics and prevention at the Dana-Farber Cancer Institute, Boston. Dr. Garber moderated a press briefing where Ms. Bolton discussed her findings,

Ms. Bolton had no relevant disclosures.

ORLANDO - Ovarian cancer patients with BRCA1 or BRCA2 gene mutations have better survival than do those with neither mutation, and those with the BRCA2 mutation have better survival than do those with the BRCA1 mutation, according to the findings of a large, multicenter study.

The findings confirm the results of several prior smaller studies showing a survival advantage in mutation carriers vs. nonmutation carriers, and they provide the first direct evidence that BRCA1 and BRCA2 mutations have differing effects on survival, Kelly L. Bolton reported at the annual meeting of the American Association for Cancer Research.

She and her colleagues studied 3,531 women with invasive epithelial ovarian cancer who were enrolled in one of 24 studies in the United States, Europe, Israel, and Asia, and for whom survival data were available. They excluded patients who either were known or were likely not to have received platinum-based therapy. Included were 1,178 women with BRCA1, 367 with BRCA2, and 1,986 who were BRCA negative.

The 5-year survival was 36% in those with no mutation, 46% of those with the BRCA1 mutation, and 61% of those with the BRCA2 mutation, after adjustment for stage, grade, histology, and age at diagnosis, said Ms. Bolton, a predoctoral fellow at the National Cancer Institute.

The difference in survival between the BRCA1 mutation carriers and those with no mutation was modest, although not statistically significant (hazard ratio, 0.84). However, the difference between the BRCA2 mutation carriers and both the noncarriers and the BRCA1 mutation carriers (after adjustment for age at diagnosis) did reach statistical significance (HR, 0.57 and 0.69, respectively).

Even after the exclusion of all but high-grade, advanced-stage serous cases, the survival differences persisted, Ms. Bolton reported.

A possible explanation for the differences, based on in vitro work and some retrospective trials, may lie in patients’ responses to chemotherapy; those with the BRCA2 mutation may have an improved response, but unidentified biological differences among BRCA1 carriers, BRCA2 carriers, and noncarriers could also be driving the association, she said.

The BRCA1 and BRCA2 mutation carriers in this study did not differ in regard to tumor stage, grade, or histology. Compared with noncarriers, however, BRCA1 carriers were younger and BRCA2 carriers were older at diagnosis.

Furthermore, compared with noncarriers, BRCA1 and BRCA2 carriers were more likely to present with advanced-stage disease, high-grade disease, and serous disease.

"The findings don’t have any immediate impact on clinical practice, but they do have important implications [for both] clinical prediction and also trial design, particularly for clinical trials," Ms. Bolton said, noting that although germline mutations in the BRCA1 and BRCA2 genes (which are important in DNA damage repair and have distinct yet complementary functions) are rare in the general population, they are present in 10%-15% of those with ovarian cancer.

Indeed, the findings – which "may be a very faint silver lining" for mutation carriers with a terrible disease that still has terrible survival – do speak to the possibility that women with these mutations need to be identified in the setting of ovarian cancer, as the presence of mutations will affect thinking about treatment, said Dr. Judy E. Garber, the new AACR president and director of the center for cancer genetics and prevention at the Dana-Farber Cancer Institute, Boston. Dr. Garber moderated a press briefing where Ms. Bolton discussed her findings,

Ms. Bolton had no relevant disclosures.