Abstract 06: A genetic risk predictor for breast cancer using a combination of low-penetrance polymorphisms in a Japanese population.

Abstract

Abstract Genome-wide association studies (GWASs) have identified genetic variants associated with breast cancer. Most GWASs to date have been conducted in women of European descent, however, and the contribution of these variants as predictors in Japanese women is unknown. Here, we analyzed 79 genetic variants identified in previous GWASs and conducted a case–control study with 697 case subjects and 1,394 age- and menopausal status-matched controls. We fit conditional regression models with genetic variants and conventional risk factors. In addition, we created a polygenetic risk score, using those variants with a statistically significant association with breast cancer risk, and also evaluated the contribution of these genetic predictors using the c statistic. Twenty-three single nucleotide polymorphisms (SNPs) revealed significant associations with breast cancer risk. A dose-dependent association was observed between the risk of breast cancer and the genetic risk score, which was an aggregate measure of alleles in seven selected variants. Compared to women with scores of 33 to 35, odds ratios (ORs) for women with scores of 23–25, 26–29, 30–32, and 10 or more were 1.28 (95% confidence interval, 0.93-1.76), 2.16 (1.61-2.95), 3.17 (2.07-4.87), and 7.7 (2.69-22.0), respectively (Ptrend = 1.28 × 10−13). The c statistic for a model including the genetic risk score in addition to the conventional risk factors was 0.726, versus 0.675 with the conventional risk factors only (P<0.0001). In conclusion, we identified a genetic risk predictor of breast cancer in a Japanese population. Risk models which include a genetic risk score are possibly useful in distinguishing women at high risk of breast cancer from those at low risk, particularly in the context of targeted prevention. Citation Format: Hidemi Ito, Aiko Sueta, Hiroji Iwata, Satoyo Hosono, Isao Oze, Miki Watanabe, Hirotaka Iwase, Hideo Tanaka, Keitaro Matsuo. A genetic risk predictor for breast cancer using a combination of low-penetrance polymorphisms in a Japanese population. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 06.