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Variation in selenoenzyme genes and prostate cancer risk and survival.

ABSTRACT: 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.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.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.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.

SUBMITTER: Geybels MS

PROVIDER: S-EPMC3859305 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Variation in selenoenzyme genes and prostate cancer risk and survival.

Geybels Milan S MS Hutter Carolyn M CM Kwon Erika M EM Ostrander Elaine A EA Fu Rong R Feng Ziding Z Stanford Janet L JL Peters Ulrike U

The Prostate 20121109 7

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 23143801

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Project description:BACKGROUND:Previous research indicates increased prostate cancer risk for pesticide applicators and pesticide manufacturing workers. Although underlying mechanisms are unknown, evidence suggests a role of oxidative DNA damage. OBJECTIVES:Because base excision repair (BER) is the predominant pathway involved in repairing oxidative damage, we evaluated interactions between 39 pesticides and 394 tag single-nucleotide polymorphisms (SNPs) for 31 BER genes among 776 prostate cancer cases and 1,444 male controls in a nested case-control study of white Agricultural Health Study (AHS) pesticide applicators. METHODS:We used likelihood ratio tests from logistic regression models to determine p-values for interactions between three-level pesticide exposure variables (none/low/high) and SNPs (assuming a dominant model), and the false discovery rate (FDR) multiple comparison adjustment approach. RESULTS:The interaction between fonofos and rs1983132 in NEIL3 [nei endonuclease VIII-like 3 (Escherichia coli)], which encodes a glycosylase that can initiate BER, was the most significant overall [interaction p-value (pinteract) = 9.3 × 10-6; FDR-adjusted p-value = 0.01]. Fonofos exposure was associated with a monotonic increase in prostate cancer risk among men with CT/TT genotypes for rs1983132 [odds ratios (95% confidence intervals) for low and high use compared with no use were 1.65 (0.91, 3.01) and 3.25 (1.78, 5.92), respectively], whereas fonofos was not associated with prostate cancer risk among men with the CC genotype. Carbofuran and S-ethyl dipropylthiocarbamate (EPTC) interacted similarly with rs1983132; however, these interactions did not meet an FDR < 0.2. CONCLUSIONS:Our significant finding regarding fonofos is consistent with previous AHS findings of increased prostate cancer risk with fonofos exposure among those with a family history of prostate cancer. Although requiring replication, our findings suggest a role of BER genetic variation in pesticide-associated prostate cancer risk.

Project description:BackgroundWe previously found that inflammation in benign prostate tissue is associated with an increased odds of prostate cancer, especially higher-grade disease. Since part of this link may be due to genetics, we evaluated the association between single nucleotide polymorphisms (SNPs) in immune response genes and prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial.MethodsWe genotyped 16 candidate SNPs in IL1β, IL2, IL4, IL6, IL8, IL10, IL12(p40), IFNG, MSR1, RNASEL, TLR4, and TNFA and seven tagSNPs in IL10 in 881 prostate cancer cases and 848 controls negative for cancer on an end-of-study biopsy. Cases and controls were non-Hispanic white and frequency matched on age and family history. We classified cases as lower (Gleason sum <7; N = 674) and higher (7-10; N = 172) grade, and used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusting for age and family history.ResultsThe minor allele (C) of rs3212227 in IL12(p40) was associated with an increased risk of total (log additive: OR = 1.30, 95%CI 1.10-1.53; P-trend = 0.0017) and lower-grade (OR = 1.36, 95%CI 1.15-1.62; P-trend = 0.0004) prostate cancer. The minor allele (A) of rs4073 in IL8 was possibly associated with a decreased risk of higher-grade (OR = 0.81, 95%CI 0.64-1.02; P-trend = 0.07), but not total disease. None of the other candidates was associated with risk. The minor alleles of IL10 tagSNPs rs1800890 (A; OR = 0.87, 95%CI: 0.75-0.99; P-trend = 0.04) and rs3021094 (C; OR = 1.31, 95%CI 1.03-1.66, P-trend = 0.03) were associated with risk; the latter also with lower- (P-trend = 0.04) and possibly higher- (P-trend = 0.06) grade disease. These patterns were similar among men with PSA <2 ng/ml at biopsy.ConclusionVariation in some immune response genes may be associated with prostate cancer risk. These associations were not fully explained by PSA-associated detection bias. Our findings generally support the role of inflammation in the etiology of prostate cancer.

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Variation in selenoenzyme genes and prostate cancer risk and survival.

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Variation in selenoenzyme genes and prostate cancer risk and survival.

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