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

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Abstract

Background: The contribution of non-inherited factors, including lifestyle factors, towards the risk of breast cancer in women and its relationship with their genetic makeup is only partly characterised. This study illustrates these effects within UK females in large population based cohort using current genetic stratification. Methods: Data from UK biobank, a prospective cohort relating to 2,728 patients with breast cancer and 88,489 women without breast cancer were analysed. The median follow up time for the cohort was 10 years (maximum 13 years). The dataset used for the analysis was ‘frozen’ at March 2019. The analysis was restricted to post-menopausal white females. Classification of ‘healthy lifestyle’ was based on Cancer Research UK guidance of (healthy weight, regular exercise, no HRT use, no oral contraceptive use, alcohol intake of < three times a week). Three groups were established: favourable (at least 4 healthy factors), intermediate (2-3 healthy factors), and unfavourable (one or none of healthy factors). The genetic contribution was estimated using the polygenic scores (PRS) of a pre-selected 305 single nucleotide polymorphisms (SNPs). PRS were categorized into three tertiles. Cox proportional-hazard regression was used to assess the hazard ratios (HR) of the lifestyles and PRS against breast cancer. High PRS and unfavourable lifestyles were both independently associated with increased risk of breast cancer. Results: Mean age of patients was 60.1 years while controls was 59.4. The BC patients were having higher BMI, doing less exercise, used HRT for longer than 5 years, used more oral contraceptives, and drank more alcohol compared to the controls. Overall, 23.2% of females followed a ‘favourable lifestyle’, 68.0% followed an ‘intermediate lifestyle’, and 8.8% followed an ‘unfavourable lifestyle’. The relative risk of the highest genetic risk group was 2.55 (95% CI; 2.28-2.84) and the RR of the most unfavourable lifestyle category was 1.44 (95% CI; 1.25-1.65). The association of lifestyle and breast cancer within genetic subgroups showed lower HR among females following favourable lifestyle compared to intermediate and unfavourable lifestyles among all the genetic groups. Women with an unfavourable lifestyle had a higher risk of BC with a HR = 1.63 (95% CI: 1.13-2.34) in the low genetic group, HR=1.94 (95% CI: 1.46-2.58) in the intermediate genetic group, and HR= 1.39 (95% CI: 1.11-1.74) in the high genetic group compared to the reference group of favourable lifestyle. Intermediate lifestyle was also associated with a higher risk of BC with HR= 1.40 (95% CI: 1.09-1.80) among the low genetic group and HR= 1.37 (95% CI: 1.09-1.72) among the intermediate genetic group. Conclusion: In this cohort study of data on women in the UK Biobank, those who followed a healthier lifestyle with more exercise, healthy weight, low alcohol intake, and no contraceptive or no or limited HRT use were associated with a reduced level of risk for breast cancer, even if they were of higher genetic risk for breast cancer.

Bibliographical metadata

Original languageEnglish
JournalJAMA Network Open
Publication statusAccepted/In press - 26 Feb 2020