Ataxia telangiectasia-mutated rs56009889 and risk of common cancers.

Abstract

A polymorphic variant in the ataxia telangiectasia-mutated (ATM) gene, rs56009889, was recently associated with an increased risk of lung cancer. We studied the role of this variant in the etiology of other cancers. Data from three population-based case-control studies of colon, breast, and lung cancer were used. Participants in these studies (4517 cases, 3383 controls) underwent a genome-wide association study using 500K Illumina OncoArray. The frequency of the AG/AA genotypes differed between Ashkenazi (4.6%) and Sephardi (0.2%) Jews (P < 0.001). AG/AA frequency was significantly higher in Ashkenazi lung cancer (11.9%) than in controls (2.8%) [adjusted odds ratio (OR) = 5.4]. Females had a higher risk than males (OR = 12.8 versus 3.5). The adjusted OR for colorectal cancer was 1.40 [95% confidence interval (CI) = 1.01-2.0, P = 0.045] and for breast cancer was 1.43 (95% CI = 1.01-2.04, P = 0.046). Never-smokers variant carriers were at higher risk of lung and colon, but not breast, cancer. Cases with the AG/AA genotype had lower mean age at diagnosis, but this difference was significant only for breast cancer (-3.2 years, P = 0.007). No associations were observed with overall survival. Among the breast cancer subjects, the OR for having triple-negative tumors was 0.45 for AG/AA versus GG genotype (95% CI = 0.2-0.9, P = 0.02). We confirm the strong association between ATM rs56009889 and lung cancer risk in Ashkenazi Jews and report a mild association with the risk of breast cancer and colorectal cancer.