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Variation in selenoenzyme genes and prostate cancer risk and survival
Author(s) -
Geybels Milan S.,
Hutter Carolyn M.,
Kwon Erika M.,
Ostrander Elaine A.,
Fu Rong,
Feng Ziding,
Stanford Janet L.,
Peters Ulrike
Publication year - 2013
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22617
Subject(s) - single nucleotide polymorphism , selenoprotein , oncology , odds ratio , proportional hazards model , medicine , prostate cancer , biology , genetics , cancer , gene , genotype , glutathione peroxidase , catalase , oxidative stress
BACKGROUND While several studies showed that selenium may prevent prostate cancer (PCa), few studies have evaluated variation in selenoenzyme genes in relation to PCa risk and survival. METHODS We studied common variants in seven selenoenzymes genes in relation to risk of PCa and PCa‐specific mortality (PCSM). In a population‐based case–control study of men of European ancestry (1,309 cases, 1,266 controls), we evaluated 35 common, tagging single nucleotide polymorphisms (SNPs) in GPX1 (n = 2), GPX2 (n = 4), GPX3 (n = 6), GPX4 (n = 6), SEP15 (n = 4), SEPP1 (n = 6), and TXNRD1 (n = 7) in relation to PCa risk, and among cases, associations between these variants and risk of PCSM. We used logistic regression and Cox proportional hazards regression to estimate the relative risk of PCa and PCSM, respectively. RESULTS Of the SNPs examined, only GPX1 rs3448 was associated with overall PCa risk with an odds ratio of 0.62 for TT versus CC (95% confidence interval, 0.44–0.88). SNPs in GPX2 , GPX3 , GPX4 , SEP15 , and SEPP1 had different risk estimates for PCa in subgroups based on stage and grade. We observed associations between SNPs in GPX4 , and TXNRD1 and risk of PCSM. None of these associations, however, remained significant after adjustment for multiple comparisons. CONCLUSIONS We found evidence that genetic variation in a subset of selenoenzyme genes may alter risk of PCa and PCSM. These results need validation in additional subsets. Prostate 73: 734–742, 2013. © 2012 Wiley Periodicals, Inc.