Associations between ERα, ERβ, and AR Genotypes and Colon and Rectal Cancer

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Abstract
Estrogen and androgens are thought to be involved in the etiology of colorectal cancer. We evaluate genetic variants of the estrogen receptor genes (ERα and ERβ) and the androgen receptor gene (AR). We use data from two large case-control studies of colon (n = 1,580 cases and 1,968 controls) and rectal (n = 797 cases and 1,016 controls) cancer. We evaluated the 351A>G XbaI polymorphism of ERα, the 1,082 G>A and CA repeat polymorphisms of ERβ, and the CAG repeat of AR. Having two 25 or more CA repeats in ERβ was associated with an increased relative risk of colon cancer in women [odds ratio (OR), 2.13; 95% confidence interval (95% CI), 1.24-3.64] but not in men (Pinteraction relative excess risk from interaction < 0.01; multiplicative = 0.03). Increasing number of AR CAG repeats was directly associated with colon cancer among men (OR, 1.28; 95% CI, 1.06-1.54), but not women (OR, 0.83; 95% CI, 0.68-1.02); the interaction P value for AR gene × sex was R allele of the ERβ gene, whereas an R allele was associated with increased risk among postmenopausal women who did not take HRT. Postmenopausal women not using HRT who had ≥25 CA repeats of the ERβ gene had over a 6-fold increased risk of colon cancer (OR, 6.71; 95% CI, 2.89-15.6). Our results suggest that the ERβ gene is more important than ERα in the etiology of colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2936–42)