182P Association of non-genetic factors with breast cancer risk in genetically predisposed groups of women in the UK Biobank cohort

The association between non-inherited 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. This study examined the association between healthier lifestyle habits and BC risk in genetically predisposed groups. Classification of healthy lifestyle was based on Cancer Research UK guidance (healthy weight, regular exercise, no use of HRT for >5 years, no OC use, 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 PRS of 305 preselected SNPs.Cox proportional hazards regression was used to assess the hazard ratios (HRs) of the lifestyles and PRS associated with a malignant neoplasm of the breast. 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). A healthier lifestyle appeared to be associated with a reduced level of risk for BC, even if the women were at higher genetic risk for BC.