A single nucleotide polymorphism (SNP), rs6983267, in the chromosome 8q24 region, has been associated with higher risk for colorectal neoplasms, but its role in carcinogenesis is unclear. To investigate whether rs6983267 genotype modifies associations of traditional lifestyle risk factors for colorectal neoplasms with colorectal adenoma, we performed a pooled analysis from three, previously-conducted, colonoscopy-based, case-control studies of incident, sporadic colorectal adenoma conducted in Minnesota, North Carolina, and South Carolina between 1991 and 2002, among the White participants (n = 401 cases, 518 controls). Demographic, dietary, and other lifestyle information was collected via mailed questionnaires (including a Willett food frequency questionnaire) before colonoscopy, blood samples were collected at colonoscopy, and rs6983267 genotyping was conducted using a Taqman genotyping platform. Associations were assessed using unconditional multivariable logistic regression models. Consistent with previous studies, compared to the TT genotype, the odds ratios (ORs) for those with the GT and GG genotypes were, respectively, 1.23 (95% confidence interval [CI] 0.86-1.77) and 1.84 (CI 1.24-2.75), after adjusting for age, sex, and family history of colorectal cancer in a first degree relative. We found no clear indications of effect modification by 8q24 genotypes on the associations between the following risk factors and colorectal adenoma: age, body mass index (BMI), tobacco or alcohol use, physical activity, nonsteroidal anti-inflammatory drug (NSAID) use, use of hormone replacement therapy among women, blood 25-OH-vitamin D3 levels, oxidative balance score, or total energy, red meat, vegetable and fruit, calcium, and folate intakes. Consistent with these findings, none of the genotype-risk factor interaction terms was statistically significant, after adjustment for multiple testing. However, there were some suggestions that associations of adenomas may have been stronger with 1) NSAIDs among those homozygous for the high risk G allele, and 2) total calcium intake and blood 25-OH-vitamin D3 among those with at least one T allele. These findings, together with previously reported null results on 8q24-environment interactions in relation to colorectal cancer, suggest that 8q24 genotypes may not modify associations of colorectal neoplasms with most traditional risk factors for the disease. However, our findings do provide support for further investigation in a larger, preferably prospective study of whether associations of calcium intakes, blood 25-OH-vitamin D3, and NSAID use with incident, sporadic colorectal adenoma may differ according to 8q24 genotypes.

Citation Format: Baiyu Yang, Bharat Thyagarajan, Myron D. Gross, Veronika Fedirko, Michael Goodman, Roberd M. Bostick. No evidence that associations of major lifestyle risk factors with incident, sporadic colorectal adenoma are modified by chromosome 8q24 region rs6983267 genotype. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4833. doi:10.1158/1538-7445.AM2013-4833