title: DNA base excision repair genetic risk scores, oxidative balance, and incident, sporadic colorectal adenoma.
abstract: Associations of individual base excision repair (BER) genotypes with colorectal adenoma risk are unclear, but likely modest. However, genetic risk scores (GRS) that aggregate information from multiple genetic variants might be useful for assessing genetic predisposition to colorectal adenoma. We analyzed data pooled from three colonoscopy-based case-control studies of incident, sporadic colorectal adenoma (n = 488 cases, 604 controls) that collected blood for genotyping and extensive dietary and other data. We randomly split our population sample into training samples (half of the participants) and validation samples (the remaining participants) 10 times. Associations of 65 individual single nucleotide polymorphisms (SNPs) in 15 BER genes were assessed in the training samples and used to combine information from multiple risk variants into a BER GRS among the validation samples using unweighted and weighted methods. We also combined 15 extrinsic exposures with known pro- or antioxidant properties into an oxidative balance score (OBS). Associations of the BER GRS with colorectal adenoma, overall and jointly with the OBS, were assessed using multivariable logistic regression. The odds ratio for those in the highest relative to the lowest tertile of the weighted BER GRS was 2.07 (95% confidence interval, 1.26-3.40; ptrend= 0.01). Relative to those with both a low GRS and a high (more antioxidant) OBS, the estimated direct association for those with both a high BER GRS and a low OBS was stronger than for those in other GRS/OBS categories. Our findings suggest that BER genotypes collectively may be associated with incident sporadic colorectal adenomas.
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, North Carolina.|Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia.
authors.forename: Tengteng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia.
authors.forename: Michael
authors.initials: M
authors.lastname: Goodman
authors.affiliation: Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia.
authors.forename: Yan V
authors.initials: YV
authors.lastname: Sun
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Bharat
authors.initials: B
authors.lastname: Thyagarajan
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Myron
authors.initials: M
authors.lastname: Gross
authors.affiliation: Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia.|Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Roberd M
authors.initials: RM
authors.lastname: Bostick
mesh_terms: D000236:Adenoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D004260:DNA Repair; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; D012007:Rectum / Q000473:pathology; D012307:Risk Factors
keywords: DNA base excision repair; colorectal adenoma; genetic risk score; oxidative balance; single nucleotide polymorphisms