Abstract 963: The interplay between lifestyle-related factors and genetics with risk of invasive breast cancer among postmenopausal women from the UK Biobank

Abstract

Abstract Background: Many genetic variants have been associated with increased risk of breast cancer. In contrast, an overall healthy lifestyle has been associated with a reduced risk. However, the degree to which an overall healthy lifestyle may attenuate the impact of genetic variants on risk of breast cancer remains equivocal. In this study, we examined the association of a healthy lifestyle index (HLI) with risk of breast cancer by genetic risk groups. Methods: The study included 106,814 postmenopausal women of white descent aged 40 to 70 years who were enrolled in the UK Biobank cohort between 2006 and 2010. The HLI was based on a combination of diet, physical activity, smoking, alcohol consumption and anthropometry (ranging from 0 to 20, with the higher scores representing more favorable lifestyle). A polygenic risk score (categorized as low, intermediate and high) was generated as the sum of risk alleles weighted by the logOR of 117 breast cancer associated single nucleotide polymorphisms. A total of 1,949 incident invasive breast cancer cases were ascertained after a median follow-up of 5.7 years. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the association of a healthy lifestyle risk score with risk of breast cancer by genetic risk groups. Results: Compared to women with an unfavorable lifestyle (lowest quartile), women with a favorable lifestyle (highest quartile) had a 32% reduced risk of invasive breast cancer (HR: 0.68: 0.59, 0.79). Women with high genetic risk (highest tertile) had an 86% increased risk of invasive breast cancer (1.86: 1.66, 2.08) compared to those with low genetic risk (lowest tertile). Compared with women who had an unfavorable lifestyle, a favorable lifestyle did not significantly reduce risk of invasive breast cancer among women with low genetic risk (0.80: 0.63-1.02), while women with a favorable lifestyle had 32% and 43% reduced risk of invasive breast cancer in the intermediate and high genetic risk categories, respectively (0.68: 0.53, 0.86 and 0.57; 0.44, 0.74, respectively). However, interaction between the genetic score and the lifestyle score did not achieve statistical significance (pinteraction=0.162). Conclusion: This study suggests that an overall healthy lifestyle may attenuate the impact of genetics on risk of breast cancer, particularly among women with intermediate and high genetic risk. Citation Format: Rhonda S. Arthur, Tao Wang, Thomas Rohan. The interplay between lifestyle-related factors and genetics with risk of invasive breast cancer among postmenopausal women from the UK Biobank [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 963.