Confirmation of genetic variants associated with lethal prostate cancer in a cohort of men from hereditary prostate cancer families. Issue 9 (13th October 2014)

• Record Type: Journal Article
• Authors: Karyadi, Danielle M.; Zhao, Shanshan; He, Qianchuan; McIntosh, Laura; Wright, Jonathan L.; Ostrander, Elaine A.; Feng, Ziding; Stanford, Janet L.
• Is Part Of: International journal of cancer. Volume 136:Issue 9(2015:May 01)
• Page Start: 2166
• Page End: 2171
• Publication Date: 2014-10-13
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29241
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Germline genetic variants have been suggested as prognostic biomarkers for identifying patients at high risk for lethal prostate cancer (PCa). Validation studies have confirmed the association of several single nucleotide polymorphisms (SNPs) with fatal PCa, but whether these variants affect PCa‐specific mortality (PCSM) in patients with an inherited predisposition to PCa, based on familial history, is unknown. For this study, a cohort of 957 PCa patients from 270 hereditary prostate cancer families of European ancestry was genotyped for a panel of 22 PCSM‐associated SNPs. Death certificates were reviewed to confirm cause of death. Mixed‐effect Cox proportional hazards models were used to assess survival according to genotypes, accounting for relatedness and clinicopathological factors. Within this cohort, 98 PCa deaths were confirmed over an average follow‐up period of 12.7 years after diagnosis. Variant allele carriers for three SNPs had significantly altered risk for PCSM [rs635261 at <italic>RNASEL</italic>, hazard ratio (HR), 0.35, 95% CI, 0.18–0.66; <italic>p</italic> = 0.002; rs915927 in <italic>XRCC1, </italic> HR, 1.91, 95% CI, 1.21–3.02; <italic>p</italic> = 0.009; and rs2494750 at <italic>AKT1</italic>, HR, 0.45, 95% CI, 0.23–0.90; <italic>p</italic> = 0.016). These results confirm the association of genetic variation in three genes with PCa lethality in a cohort of men with an inherited susceptibility to the disease and provide validation evidence that germline SNPs provide prognostic information for PCa patients. Development of a panel of germline biomarkers with clinical utility for distinguishing patients at detection who have an increased risk for fatal PCa is warranted.</p> </abstract>