Association of Nongenetic Factors With Breast Cancer Risk in Genetically Predisposed Groups of Women in the UK Biobank Cohort.

This cohort study examines the association of nongenetic factors, such as lifestyle habits, with risk of breast cancer in women with varying levels of genetic predisposition for developing the disease. Question Is adhering to healthier lifestyle habits associated with a reduced breast cancer risk even among genetically predisposed groups? Findings This cohort study evaluated 2728 women with breast cancer and 88 & x202f;489 controls and noted lower risks of breast cancer among women who practice a healthy lifestyle. Factors included in this lifestyle were exercise, healthy weight, low alcohol intake, and no oral contraceptive use, as well as avoiding or limiting use of hormonal replacement therapy to less than 5 years, among low, intermediate, and high genetic risk groups. Meaning Following a healthier lifestyle appears to be associated with a decreased level of risk of breast cancer across all strata of genetic risk. Importance The association between noninherited factors, including lifestyle factors, and the risk of breast cancer (BC) in women and the association between BC and genetic makeup are only partly characterized. A study using data on current genetic stratification may help in the characterization. Objective To examine the association between healthier lifestyle habits and BC risk in genetically predisposed groups. Design, Setting, and Participants Data from UK Biobank, a prospective cohort comprising 2728 patients with BC and 88 & x202f;489 women without BC, were analyzed. The data set used for the analysis was closed on March 31, 2019. The analysis was restricted to postmenopausal white women. Classification of healthy lifestyle was based on Cancer Research UK guidance (healthy weight, regular exercise, no use of hormone replacement therapy for more than 5 years, no oral contraceptive use, and alcohol intake <3 times/wk). Three groups were established: favorable (>= 4 healthy factors), intermediate (2-3 healthy factors), and unfavorable (<= 1 healthy factor). The genetic contribution was estimated using the polygenic risk scores of 305 preselected single-nucleotide variations. Polygenic risk scores were categorized into 3 tertiles (low, intermediate, and high). Main Outcomes and Measures Cox proportional hazards regression was used to assess the hazard ratios (HRs) of the lifestyles and polygenic risk scores associated with a malignant neoplasm of the breast. Results Mean (SD) age of the 2728 women with BC was 60.1 (5.5) years, and mean age of the 88 & x202f;489 women serving as controls was 59.4 (4.9) years. The median follow-up time for the cohort was 10 years (maximum 13 years) (interquartile range, 9.44-10.82 years). Women with BC had a higher body mass index (relative risk [RR], 1.14; 95% CI, 1.05-1.23), performed less exercise (RR, 1.12; 95% CI, 1.01-1.25), used hormonal replacement therapy for longer than 5 years (RR, 1.23; 95% CI, 1.13-1.34), used more oral contraceptives (RR, 1.02; 95% CI, 0.93-1.12), and had greater alcohol intake (RR, 1.11; 95% CI, 1.03-1.19) compared with the controls. Overall, 20 657 women (23.3%) followed a favorable lifestyle, 60 195 women (68.0%) followed an intermediate lifestyle, and 7637 women (8.6%) followed an unfavorable lifestyle. The RR of the highest genetic risk group was 2.55 (95% CI, 2.28-2.84), and the RR of the most unfavorable lifestyle category was 1.44 (95% CI, 1.25-1.65). The association of lifestyle and BC within genetic subgroups showed lower HRs among women following a favorable lifestyle compared with intermediate and unfavorable lifestyles among all of the genetic groups: women with an unfavorable lifestyle had a higher risk of BC in the low genetic group (HR, 1.63; 95% CI, 1.13-2.34), intermediate genetic group (HR, 1.94; 95% CI, 1.46-2.58), and high genetic group (HR, 1.39; 95% CI, 1.11-1.74) compared with the reference group of favorable lifestyle. Intermediate lifestyle was also associated with a higher risk of BC among the low genetic group (HR, 1.40; 95% CI, 1.09-1.80) and the intermediate genetic group (HR, 1.37; 95% CI, 1.12-1.68). Conclusions and Relevance In this cohort study of data on women in the UK Biobank, a healthier lifestyle with more exercise, healthy weight, low alcohol intake, no oral contraceptive use, and no or limited hormonal replacement therapy use appeared to be associated with a reduced level of risk for BC, even if the women were at higher genetic risk for BC.