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Background: Genome-wide association studies (GWAS) have led to the identification of a number of common susceptibility loci for colorectal cancer (CRC); however, none of these GWAS have considered gene-environment (G × E) interactions. Therefore, it is unclear whether current hits are modified by environmental exposures or whether there are additional hits whose effects are dependent on environmental exposures., Methods: We conducted a systematic search for G × E interactions using genome wide data from the Colon Cancer Family Registry that included 1,191 cases of microsatellite stable (MSS) or microsatellite instability-low (MSI-L) CRC and 999 controls genotyped using either the Illumina Human1M or Human1M-Duo BeadChip. We tested for interactions between genotypes and 14 environmental factors using 3 methods: a traditional case-control test, a case-only test, and the recently proposed 2-step method by Murcray and colleagues. All potentially significant findings were replicated in the ARCTIC Study., Results: No G × E interactions were identified that reached genome-wide significance by any of the 3 methods. When analyzing previously reported susceptibility loci, 7 significant G × E interactions were found at a 5% significance level. We investigated these 7 interactions in an independent sample and none of the interactions were replicated., Conclusions: Identifying G × E interactions will present challenges in a GWAS setting. Our power calculations illustrate the need for larger sample sizes; however, as CRC is a heterogeneous disease, a tradeoff between increasing sample size and heterogeneity needs to be considered., Impact: The results from this first genome-wide analysis of G × E in CRC identify several challenges, which may be addressed by large consortium efforts., (©2011 AACR.)

Few studies have assessed the relation between dietary patterns and gastric adenocarcinoma risk, yet this approach has advantages over single-nutrient analysis, including the ability to reflect eating patterns in populations and ease of implementing dietary recommendations. The authors evaluated associations between dietary patterns, a food index score, and incident gastric cancer risk in a Canadian study of 1,169 cases and 2,332 controls (1995-1997). Dietary patterns were assessed via factor analysis applied to a food frequency questionnaire. A food index score was derived based on risk factors for gastric cancer. A multivariable-adjusted prudent dietary pattern was associated with decreased risk of gastric cancer in women (odds ratio (OR) = 0.58, 95% confidence interval (CI): 0.37, 0.92); a Western dietary pattern was associated with increased risk in women (OR = 1.86, 95% CI: 1.20, 2.89) and men (OR = 1.44, 95% CI: 1.03, 2.02). The food index score was associated with decreased risk among women (OR = 0.40, 95% CI: 0.27, 0.59) and men (OR = 0.63, 95% CI: 0.45, 0.88). Dietary patterns especially characterized by Western features (soft drinks, processed meats, refined grains, and sugars) were associated with increased risk of gastric adenocarcinoma, whereas dietary patterns characterized by increased consumption of fruits, vegetables, and fish were associated with lessened risk.

Overweight and obesity are linked with several chronic diseases, including colorectal cancer, among men, but results among women are equivocal. Previous evidence suggests that menopausal status, postmenopausal hormone use, and family history of cancer may modify the link between adiposity and colorectal cancer. In data from two population-based case-control studies (cases: 1,292 males and 1,404 females; controls: 1,465 males and 1,203 females) in Ontario and Newfoundland, Canada, we examined the link between colorectal cancer and body mass index (BMI) at two reference periods (BMI 2 years prior and BMI at age 20 years), weight gain since age 20 years, and height. Based on recent BMI indices among men, obesity (BMI >/=30 kg/m(2)) was associated with an 80% [95% confidence interval (95% CI), 1.43-2.27] increased risk of colorectal cancer relative to a normal BMI (18.5-24.9 kg/m(2)). The same comparison for BMI at age 20 years suggested a 94% increased risk of colorectal cancer (95% CI, 1.19-3.16). Odds ratios were similar among subgroups of men with and without a clinically defined familial risk of cancer (according to the Amsterdam or revised Bethesda criteria for Lynch syndrome). Associations were moderately stronger for cancer of the colon than cancer of the rectum. Among women, BMI and weight gain were not linked with colorectal cancer; the null associations were persistent in subgroups of familial risk of cancer, menopausal status, estrogenic status, and subsite. Tall height (>1.75 m), however, was linked with increased risk of colorectal cancer among women (odds ratio, 2.27; 95% CI, 1.46-3.59) but not among men. This study suggests that obesity is associated with increased risk of sporadic and Lynch syndrome-related colon and rectal cancers among men but not among women, whereas height is directly linked with all such cancers among women but not among men.

Physical inactivity is linked to risk for cancers of the colon, breast, lung and endometrium, but few data exist on this association with stomach cancer. We evaluated the association between recreational physical activity and incident stomach cancer in a case-control study. The data yielded odds ratios suggestive of approximately 20-40% reduced risk of stomach cancer when comparing more frequent (3+ times/week) to less frequent (<1/month) strenuous activities. The magnitudes of the associations for strenuous physical activities were consistent across the teens, early 30s, and early 50s. Compared to the least active quartile, the second, third, and fourth quartiles of average lifetime strenuous physical activity yielded odds ratios of 0.82, 0.69, and 0.58 (95% CI, 0.41-0.83), respectively. Odds ratios for moderate activity generally suggested a modest, but not statistically significant, inverse association. Increased strenuous physical activity, throughout the lifespan, was associated with decreased risk of incident stomach cancer.