Genetic risk stratification of common diseases in breast cancer survivors: a population-based cohort study
TL;DR
BCa and inherited genetic susceptibility jointly contribute to increased risk of multiple common diseases, supporting the integration of genetic risk stratification into survivorship care.
Abstract
Abstract Background Patients diagnosed with breast cancer are at increased risk of multiple common diseases; however, the spectrum of these diseases and the contribution of inherited genetic susceptibility remain incompletely characterized. Methods We evaluated 15 common diseases and tested their associations with breast cancer exposure and disease-specific polygenic risk scores in the UK Biobank (n = 254 736). Analyses were performed using cause-specific Cox proportional hazards models within a full-cohort framework, with time-updated breast cancer status, delayed entry at study recruitment, and age as the underlying time scale. Results After recruitment, incident breast cancer was diagnosed in 11 386 women (4.47%), including 2742 (24.08%) with metastatic breast cancer. Patients with breast cancer had an increased risk of 9 diseases spanning cardiovascular, metabolic, and neuropsychiatric domains (P < .003, Bonferroni corrected). Elevated risks were generally observed among patients with both early-stage and advanced breast cancer. Inherited susceptibility further stratified disease risk, with the highest risks observed among patients with breast cancer and elevated disease-specific polygenic risk scores. For example, compared with women without breast cancer, the hazard ratio for osteoporosis was 2.33 (95% CI = 2.15 to 2.52) among women with any breast cancer, 2.38 (95% CI = 2.18 to 2.59) among women with nonmetastatic breast cancer, and 2.12 (95% CI = 1.78 to 2.54) among women with metastatic breast cancer; the hazard ratio was 4.48 (95% CI = 3.99 to 5.02) among patients with breast cancer in the highest quartile of osteoporosis-specific polygenic risk scores (all P < .001). In contrast, breast cancer was not statistically significantly associated with risk of coronary artery disease. Conclusion Breast cancer and inherited genetic susceptibility jointly contribute to increased risk of multiple common diseases, supporting the integration of genetic risk stratification into survivorship care.