Prostate cancer risk from occupational exposure to polycyclic aromatic hydrocarbons interacting with the GSTP1 Ile105Val polymorphism.
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AuthorsRybicki, Benjamin A.
Nock, Nora L.
Schultz, Lonni R.
Bock, Cathryn H.
Monaghan, Kristin G.
MetadataShow full item record
AbstractBACKGROUND: Variation in the glutathione S-transferase (GSTP1) gene and occupational polycyclic aromatic hydrocarbons (PAH) exposure are putative prostate cancer risk factors. An Ile/Val polymorphism in codon 105 of GSTP1 affects its enzymatic activity toward PAH detoxification, a possible mechanism in prostate carcinogenesis. METHODS: To determine whether the GSTP1 Ile105Val polymorphism modifies prostate cancer risk associated with occupational PAH exposure, we studied 637 prostate cancer cases and 244 controls of White and African-American race from the Henry Ford Health System in Detroit, Michigan. Occupational exposure to PAH from wood, petroleum, coal or other sources through respiratory and cutaneous routes was retrospectively assessed by expert review of job histories. The association of occupational PAH exposure and GSTP1 Ile105Val polymorphism with prostate cancer was tested in multiple logistic regression models adjusting for potential confounders. Cases were over sampled compared with controls to evaluate gene-environment interaction with the statistically efficient case-only analytic approach. RESULTS: Neither carriage of the GSTP1 Val(105) variant allele nor occupational PAH exposure was significantly associated with prostate cancer. However, case-only analyses revealed that carriage of the GSTP1 Val(105) variant allele was associated with increasing levels of occupational respiratory PAH exposures from any source and from petroleum (trend test p=0.01 for both). The GSTP1 Val(105) allele was observed most frequently in cases in the highest quartile of occupational respiratory PAH exposures from petroleum (OR=1.74; 95% CI=1.11-2.72) or from any source (OR=1.85; 95% CI=1.19-2.89). The gene-environment risk estimate in the highest PAH petroleum exposure quartile was greatest in men under age 60 (OR=4.52; 95% CI=1.96-10.41) or with a positive family history of prostate cancer (OR=3.02; 95% CI=1.15-7.92). CONCLUSIONS: Our results suggest men who carry the GSTP1 Val(105) variant and are exposed at high levels to occupational PAH have increased risk for prostate cancer. This increased risk is more pronounced in men under age 60 or with a family history of prostate cancer.
CitationCancer Detect. Prev. 2006, 30 (5):412-422
JournalCancer Detection and Prevention
DescriptionBiomarkers of individual susceptibility: field studies. Biomarker: GSTP1 Ile105Val polymorphismEffect studied: prostate cancer risk. Tissue/biological material/sample size: blood. Method of analysis: Invader1 or a PCR-RFLP assayStudy design: case-control studyStudy size: 637 cases and 244 controlsImpact on outcome (including dose-response): no effect of GSTP1 Val(105) variant or occupational PAH exposure individually; increased risk due to polymorphism in association with high PAH exposure: OR=1.74 (95% CI=1.11-2.72) for highest quartile of respiratory PAH exposure from petroleum; OR=1.85 (95% CI=1.19-2.8) for highest quartile of respiratory PAH exposure from any source; risk estimate in the highest PAH petroleum exposure quartile was greatest in men under age 60 (OR=4.52; 95% CI=1.96-10.41) or with a positive family history of prostate cancer (OR=3.02; 95% CI=1.15-7.92).Quality control: a) five samples were analyzed by Invader and RFLP and five samples were analyzed by two separate Invader assays with the same results obtained in all cases; b) reliability of exposure assessment was evaluated by having 56 subjects independently evaluated by 2 industrial hygienists. The results showed that the means for any of the 10 cumulative occupational PAH exposure indices used did not differ significantly between the two raters. However, intra-class correlations varied between the two raters (upto 53.1% for cutaneous petroleum exposure). Intra-class correlations for the quartiled measures of two most prevalent exposures (respiratory PAH exposures from petroleum and any source) were both at 90%.
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