Kate Gersekowski1, Rachel Delahunty2, Kathryn Alsop2, Ellen L Goode3, Julie M Cunningham4, Stacey J Winham3, Paul Pharoah5, Honglin Song6, Susan Jordan7, Sian Fereday2, Anna DeFazio8, Michael Friedlander9, Andreas Obermair10, Penelope M Webb11. 1. Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. 2. Women's Cancer Program, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria 3010, Australia. 3. Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA. 4. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. 5. Department of Public Health and Primary Care, University of Cambridge, Centre for Cancer Genetic Epidemiology, Cambridge, UK; Department of Oncology, University of Cambridge, Centre for Cancer Genetic Epidemiology, Cambridge, UK. 6. Department of Public Health and Primary Care, University of Cambridge, Cardiovascular Epidemiology Unit, Cambridge, UK. 7. School of Public Health, University of Queensland, Brisbane, Queensland, Australia. 8. Department of Gynaecological Oncology, Westmead Hospital, Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia; The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW, Australia. 9. Prince of Wales Clinical School University of New South Wales, Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia. 10. Queensland Centre for Gynaecological Cancer Research, The University of Queensland, Brisbane, Queensland, Australia. 11. Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Electronic address: penny.webb@qimrberghofer.edu.au.
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.
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.
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