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MIAMI – The fecal presence of least two genes harbored by toxin-producing or proinflammatory bacteria conferred a nearly 200% rise in the odds of colorectal adenoma, investigators reported.
Moreover, the fecal presence of usp (uropathogenic-specific protein), a bacterial gene encoding a genotoxin that damages DNA, correlated with nearly 1,200% greater odds of colorectal adenoma (P =.08), said senior investigator María González-Pons, PhD, of the University of Puerto Rico Comprehensive Cancer Center in San Juan.
“We are continuing to enlarge this study. We need more power to assess statistical significance and look at associations for individual combinations of bacterial genes,” Dr. Pons said in an interview. “Our ultimate goal is to risk-stratify patients so that we know whom to target for [colorectal cancer] prevention.”
Dr. Pons and the study’s lead author, Noe Crespo-Hernandez, of the University of Puerto Rico, presented the findings with their associates in a poster at the the annual Gut Microbiota for Health World Summit.
Colorectal cancer is the most lethal cancer and the second-most common malignancy in Puerto Rico. Despite recommendations for screening colonoscopy, many patients are diagnosed in late-stage disease, when treatment options are limited. Intestinal inflammation is itself key to colorectal carcinogenesis and also promotes the enteric proliferation of gram-negative bacteria that produce potentially carcinogenic toxins. Thus, gut inflammation and the microbiome are of great interest to researchers who are working to develop reliable, minimally invasive tests that assess future colorectal cancer risk.
For their study presented at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility, Dr. Pons and her coinvestigators compared stool samples from 67 adults with colonoscopically confirmed colorectal adenomas and 39 controls with negative screening colonoscopies. Both groups were captured in the Puerto Rico Familial Colorectal Cancer Registry. The researchers used TaqMan SNP Genotyping to look for single-nucleotide polymorphisms (SNPs) from promoter regions of genes encoding interleukin-1 beta, IL-6, and IL-10, cytokines that regulate gut inflammation. They found nonsignificant associations between colorectal adenoma and two of the three SNPs: rs143627 (encoding IL-1B) and rs1800795 (IL-6).
The real-time polymerase chain reaction results were even more striking. Using SYBR Green, the researchers tested stool for six genotoxic or proinflammatory bacterial genes and identified five, each of which correlated with colorectal adenoma. Colorectal adenoma also was linked with the fecal presence of a nonpathogenic housekeeping gene that is a surrogate for a mucolytic bacterium abundant in the stool of colorectal cancer patients.
Odds ratios for these associations ranged from 1.17 (for cnf, or cytotoxic necrotizing factor) to 12.83 (for usp), the researchers reported. Dr. Pons commented that Hurricane Maria greatly delayed this study and thus the cohort was underpowered to test for statistical significance. Nonetheless, P values approached significance for the usp gene (OR, 12.83; 95% confidence interval, 0.73-226.8; P = .08) and the fecal presence of at least two genes in combination (OR, 2.84; 95% CI, 1.01-8.90; P = .05).
Next, Dr. Pons and her team will expand the study to assess links between colorectal adenoma and these pathogenic bacterial genes, individually and in various combinations. They also plan to compare genes in normal and adenomatous colon tissue and to use enteroid (small intestinal organoid) models to tease out the carcinogenic mechanisms of these bacterial toxins.
The National Institutes of Health provided funding. The researchers disclosed no competing interests.
MIAMI – The fecal presence of least two genes harbored by toxin-producing or proinflammatory bacteria conferred a nearly 200% rise in the odds of colorectal adenoma, investigators reported.
Moreover, the fecal presence of usp (uropathogenic-specific protein), a bacterial gene encoding a genotoxin that damages DNA, correlated with nearly 1,200% greater odds of colorectal adenoma (P =.08), said senior investigator María González-Pons, PhD, of the University of Puerto Rico Comprehensive Cancer Center in San Juan.
“We are continuing to enlarge this study. We need more power to assess statistical significance and look at associations for individual combinations of bacterial genes,” Dr. Pons said in an interview. “Our ultimate goal is to risk-stratify patients so that we know whom to target for [colorectal cancer] prevention.”
Dr. Pons and the study’s lead author, Noe Crespo-Hernandez, of the University of Puerto Rico, presented the findings with their associates in a poster at the the annual Gut Microbiota for Health World Summit.
Colorectal cancer is the most lethal cancer and the second-most common malignancy in Puerto Rico. Despite recommendations for screening colonoscopy, many patients are diagnosed in late-stage disease, when treatment options are limited. Intestinal inflammation is itself key to colorectal carcinogenesis and also promotes the enteric proliferation of gram-negative bacteria that produce potentially carcinogenic toxins. Thus, gut inflammation and the microbiome are of great interest to researchers who are working to develop reliable, minimally invasive tests that assess future colorectal cancer risk.
For their study presented at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility, Dr. Pons and her coinvestigators compared stool samples from 67 adults with colonoscopically confirmed colorectal adenomas and 39 controls with negative screening colonoscopies. Both groups were captured in the Puerto Rico Familial Colorectal Cancer Registry. The researchers used TaqMan SNP Genotyping to look for single-nucleotide polymorphisms (SNPs) from promoter regions of genes encoding interleukin-1 beta, IL-6, and IL-10, cytokines that regulate gut inflammation. They found nonsignificant associations between colorectal adenoma and two of the three SNPs: rs143627 (encoding IL-1B) and rs1800795 (IL-6).
The real-time polymerase chain reaction results were even more striking. Using SYBR Green, the researchers tested stool for six genotoxic or proinflammatory bacterial genes and identified five, each of which correlated with colorectal adenoma. Colorectal adenoma also was linked with the fecal presence of a nonpathogenic housekeeping gene that is a surrogate for a mucolytic bacterium abundant in the stool of colorectal cancer patients.
Odds ratios for these associations ranged from 1.17 (for cnf, or cytotoxic necrotizing factor) to 12.83 (for usp), the researchers reported. Dr. Pons commented that Hurricane Maria greatly delayed this study and thus the cohort was underpowered to test for statistical significance. Nonetheless, P values approached significance for the usp gene (OR, 12.83; 95% confidence interval, 0.73-226.8; P = .08) and the fecal presence of at least two genes in combination (OR, 2.84; 95% CI, 1.01-8.90; P = .05).
Next, Dr. Pons and her team will expand the study to assess links between colorectal adenoma and these pathogenic bacterial genes, individually and in various combinations. They also plan to compare genes in normal and adenomatous colon tissue and to use enteroid (small intestinal organoid) models to tease out the carcinogenic mechanisms of these bacterial toxins.
The National Institutes of Health provided funding. The researchers disclosed no competing interests.
MIAMI – The fecal presence of least two genes harbored by toxin-producing or proinflammatory bacteria conferred a nearly 200% rise in the odds of colorectal adenoma, investigators reported.
Moreover, the fecal presence of usp (uropathogenic-specific protein), a bacterial gene encoding a genotoxin that damages DNA, correlated with nearly 1,200% greater odds of colorectal adenoma (P =.08), said senior investigator María González-Pons, PhD, of the University of Puerto Rico Comprehensive Cancer Center in San Juan.
“We are continuing to enlarge this study. We need more power to assess statistical significance and look at associations for individual combinations of bacterial genes,” Dr. Pons said in an interview. “Our ultimate goal is to risk-stratify patients so that we know whom to target for [colorectal cancer] prevention.”
Dr. Pons and the study’s lead author, Noe Crespo-Hernandez, of the University of Puerto Rico, presented the findings with their associates in a poster at the the annual Gut Microbiota for Health World Summit.
Colorectal cancer is the most lethal cancer and the second-most common malignancy in Puerto Rico. Despite recommendations for screening colonoscopy, many patients are diagnosed in late-stage disease, when treatment options are limited. Intestinal inflammation is itself key to colorectal carcinogenesis and also promotes the enteric proliferation of gram-negative bacteria that produce potentially carcinogenic toxins. Thus, gut inflammation and the microbiome are of great interest to researchers who are working to develop reliable, minimally invasive tests that assess future colorectal cancer risk.
For their study presented at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility, Dr. Pons and her coinvestigators compared stool samples from 67 adults with colonoscopically confirmed colorectal adenomas and 39 controls with negative screening colonoscopies. Both groups were captured in the Puerto Rico Familial Colorectal Cancer Registry. The researchers used TaqMan SNP Genotyping to look for single-nucleotide polymorphisms (SNPs) from promoter regions of genes encoding interleukin-1 beta, IL-6, and IL-10, cytokines that regulate gut inflammation. They found nonsignificant associations between colorectal adenoma and two of the three SNPs: rs143627 (encoding IL-1B) and rs1800795 (IL-6).
The real-time polymerase chain reaction results were even more striking. Using SYBR Green, the researchers tested stool for six genotoxic or proinflammatory bacterial genes and identified five, each of which correlated with colorectal adenoma. Colorectal adenoma also was linked with the fecal presence of a nonpathogenic housekeeping gene that is a surrogate for a mucolytic bacterium abundant in the stool of colorectal cancer patients.
Odds ratios for these associations ranged from 1.17 (for cnf, or cytotoxic necrotizing factor) to 12.83 (for usp), the researchers reported. Dr. Pons commented that Hurricane Maria greatly delayed this study and thus the cohort was underpowered to test for statistical significance. Nonetheless, P values approached significance for the usp gene (OR, 12.83; 95% confidence interval, 0.73-226.8; P = .08) and the fecal presence of at least two genes in combination (OR, 2.84; 95% CI, 1.01-8.90; P = .05).
Next, Dr. Pons and her team will expand the study to assess links between colorectal adenoma and these pathogenic bacterial genes, individually and in various combinations. They also plan to compare genes in normal and adenomatous colon tissue and to use enteroid (small intestinal organoid) models to tease out the carcinogenic mechanisms of these bacterial toxins.
The National Institutes of Health provided funding. The researchers disclosed no competing interests.
REPORTING FROM GUT 2019