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Germline BRCA variants, lifestyle and ovarian cancer survival

      Highlights

      • It is unknown whether associations between lifestyle factors and ovarian cancer survival differ by BRCA variant status.
      • The adverse effects of smoking on ovarian cancer survival may be stronger for women with a BRCA variant than those without.
      • There was no differential association in survival by BRCA variant status for physical activity, BMI or alcohol intake.

      Abstract

      Objective

      Women with ovarian cancer who have a pathogenic germline variant in BRCA1 or BRCA2 (BRCA) have been shown to have better 5-year survival after diagnosis than women who are BRCA-wildtype (non-carriers). Modifiable lifestyle factors, including smoking, physical activity and body mass index (BMI) have previously been associated with ovarian cancer survival; however, it is unknown whether these associations differ by germline BRCA status.

      Methods

      We investigated measures of lifestyle prior to diagnosis in two cohorts of Australian women with invasive epithelial ovarian cancer, using Cox proportional hazards regression to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).

      Results

      In the combined studies (n = 1923), there was little association between physical activity, BMI or alcohol intake and survival, and no difference by BRCA status. However, the association between current smoking status before diagnosis and poorer survival was stronger for BRCA variant carriers (HR 1.98; 95% CI 1.20–3.27) than non-carriers (HR 1.18; 95% CI 0.96–1.46; p-interaction 0.02). We saw a similar differential association with smoking when we pooled results from two additional cohorts from the USA and UK (n = 2120). Combining the results from all four studies gave a pooled-HR of 1.94 (95% CI 1.28–2.94) for current smoking among BRCA variant carriers compared to 1.08 (0.90–1.29) for non-carriers.

      Conclusions

      Our results suggest that the adverse effect of smoking on survival may be stronger for women with a BRCA variant than those without. Thus, while smoking cessation may improve outcomes for all women with ovarian cancer, it might provide a greater benefit for BRCA variant carriers.

      Keywords

      Abbreviations:

      AOCS (Australian Ovarian Cancer Study), BMI (body mass index), CI (confidence interval), FIGO (International Federation of Obstetricians and Gynecologists), MAYO (Mayo Clinic Case-Only Ovarian Cancer Study/Mayo Clinic Ovarian Cancer Case Control Study), METhrs (metabolic equivalent hours), OCAC (Ovarian Cancer Association Consortium), OPAL (Ovarian cancer Prognosis and Lifestyle), PA (physical activity), pHR (pooled hazard ratio), SEARCH (Study of Epidemiology and Risk Factors in Cancer Heredity study)
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