1. Common genetic and clinical risk factors: association with fatal prostate cancer in the Cohort of Swedish Men
- Author
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Chun Chieh Fan, Alicja Wolk, Ole A. Andreassen, Anders M. Dale, Karen Tye, Niclas Håkansson, Wesley K. Thompson, Tyler M. Seibert, Kenneth W. Muir, Artitaya Lophatananon, Ian G. Mills, Minh-Phuong Huynh-Le, and Roshan Karunamuni
- Subjects
Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Urology ,precision medicine ,030232 urology & nephrology ,survival ,Article ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Internal medicine ,Diabetes mellitus ,Epidemiology of cancer ,Cancer screening ,Biomarkers, Tumor ,Medicine ,Humans ,risk factors ,Genetic Predisposition to Disease ,genetics ,Longitudinal Studies ,Family history ,Aged ,Aged, 80 and over ,Sweden ,business.industry ,Proportional hazards model ,Prostatic Neoplasms ,medicine.disease ,Prognosis ,prostate cancer ,Survival Rate ,030220 oncology & carcinogenesis ,Case-Control Studies ,Cohort ,business ,Body mass index ,Follow-Up Studies - Abstract
Background: Clinical variables—age, family history, genetics—are used for prostate cancer risk stratification. Recently, polygenic hazard scores (PHS46, PHS166) were validated as associated with age at prostate cancer diagnosis. While polygenic scores are associated with all prostate cancer (not specific for fatal cancers), PHS46 was also associated with age at prostate cancer death. We evaluated if adding PHS to clinical variables improves associations with prostate cancer death. Methods: Genotype/phenotype data were obtained from a nested case-control Cohort of Swedish Men (n=3,279; 2,163 with prostate cancer, 278 prostate cancer deaths). PHS and clinical variables (family history, alcohol intake, smoking, heart disease, hypertension, diabetes, body mass index) were tested via univariable Cox proportional hazards models for association with age at prostate cancer death. Multivariable Cox models with/without PHS were compared with log-likelihood tests. Results: Median age at last follow-up/prostate cancer death were 78.0 (IQR: 72.3–84.1) and 81.4 (75.4–86.3) years, respectively. On univariable analysis, PHS46 (HR 3.41 [95%CI 2.78–4.17]), family history (HR 1.72 [1.46–2.03]), alcohol (HR 1.74 [1.40–2.15]), diabetes (HR 0.53 [0.37–0.75]) were each associated with prostate cancer death. On multivariable analysis, PHS46 (HR 2.45 [1.99–2.97]), family history (HR 1.73 [1.48–2.03]), alcohol (HR 1.45 [1.19–1.76]), diabetes (HR 0.62 [0.42–0.90]) all remained associated with fatal disease. Including PHS46 or PHS166 improved multivariable models for fatal prostate cancer (p
- Published
- 2021