Browsing ECNIS annotated biomarkers bibliographic database - test version by Journal
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Prostate cancer risk from occupational exposure to polycyclic aromatic hydrocarbons interacting with the GSTP1 Ile105Val polymorphism.BACKGROUND: 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.
Selected polymorphisms of DNA repair genes and risk of pancreatic cancer.BACKGROUND: Genetic variants of DNA repair genes may contribute to pancreatic carcinogenesis. O(6)-methylguanine-DNA methyltransferase (MGMT) is the major protein that removes alkylating DNA adducts, and apurinic/apyrimidinic endonuclease 1 (APE1) and X-ray repair cross-complementing group 1 (XRCC1) play important roles in the base excision repair pathway. METHODS: We investigated the association between polymorphisms of MGMT (Leu(84)Phe and Ile(143)Val), APE1 (Asp(148)Glu), and XRCC1 (Arg(194)Trp and Arg(399)Gln) and risk of pancreatic cancer in a case-control study. Exposure information from 384 patients with primary pancreatic ductal adenocarcinoma and 357 cancer-free healthy controls were collected and genomic DNAs were genotyped for five markers. Controls were frequency matched to patients by age at enrollment (+/-5 years), gender, and race. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by using unconditional logistic regression models. RESULTS: There was no significant main effect or interaction with smoking of these genetic variants on the risk of pancreatic cancer. However, the XRCC1(194) polymorphism had a significant interaction with the APE1(148) (p=0.005) or MGMT(84) polymorphism (p=0.02) in modifying the risk of pancreatic cancer. CONCLUSIONS: This study suggests that polymorphisms of genes involved in the repair of alkylating DNA adduct and DNA base damage may play a role in modulating the risk of pancreatic cancer. Larger studies are required to validate these preliminary findings. The mechanism of the combined genotype effects remains to be elucidated.