A Population-based Assessment of Germline HOXB13 G84E Mutation and Prostate Cancer Risk

摘要: Abstract Background A rare but recurrent missense mutation (G84E, rs138213197) in the gene homeobox B13 ( HOXB13 ) was recently reported to be associated with hereditary prostate cancer. Objective To explore prevalence and penetrance of G84E a general population. Design, setting, participants 14 additional polymorphisms were genotyped two population-based, Swedish, case-control samples (Cancer Prostate Sweden [CAPS] Stockholm-1) comprising 4693 controls 5003 cancer cases. CAPS collected data on patients population nationally between 2001 2003. Stockholm-1 biopsy-positive biopsy-negative Stockholm area 2005 2007. Outcome measurements statistical analysis The outcome pathologically verified Relative absolute risks among carriers explored, as combined impact disease risk polygenic score based 33 established, common, low-risk variants. Results limitations observed 1.3% strongly (CAPS: odds ratio [OR]: 3.4; 95% confidence interval [CI], 2.2–5.4; Stockholm-1: OR: 3.5; CI, 2.4–5.2). strongest association for young-onset (OR: 8.6; 5.1–14.0) 6.6; 3.3–12.0) Haplotype analyses supported that is founder mutation. have an estimated 33% (95% 23–46) cumulative age 80 yr cancer, compared 12% 11–13) noncarriers. For within top quartile established susceptibility variants, at 48% 36–64). Conclusions prevalent >1% Swedish 3.5-fold increased One-third will diagnosed which has implications surveillance carriers.