SNPs of GSTM1, T1, P1, epoxide hydrolase and DNA repair enzyme XRCC1 and risk of urinary transitional cell carcinoma in southwestern Taiwan
Journal
Toxicology and Applied Pharmacology
Journal Volume
228
Journal Issue
2
Pages
144-155
Date Issued
2008
Author(s)
Abstract
A hospital-based case-control study was conducted near a former black-foot disease (BFD)-endemic area in southwestern Taiwan to examine the possible risk factors and genetic susceptibility for urinary transitional cell carcinoma (TCC). A total of 221 patients with pathologically confirmed TCC and 223 age-sex-matched control subjects from urology outpatient clinics were recruited between 1998 and 2002. The results showed that residency in the BFD area and consumption of well water for more than 10 years was a strong factor on urinary cancer risk (odds ratio [OR],8.16, 95% confidence interval [CI],3.34-19.90, pG polymorphism was significantly associated with cancer risk (A/G+G/G: OR=0.60, 95%CI=0.39-0.94, p=0.02), and the effect of Val105 allele was largely confined to the subjects diagnosed earlier than 55 years old (A/G+G/G: OR,0.29; 95% CI, 0.09-0.87, p=0.03). The results suggest that GSTP1 is a candidate for susceptibility locus and Ile105 allele may predispose individuals to early-onset urinary TCC. The GSTM1 null genotype was associated with tumors of high-invasiveness (OR,2.21; 95% CI, 1.34-4.73) as well as with early-onset TCC risk (OR,2.53; 95% CI, 0.97-6.59). Our preliminary results showed the XRCC1 Arg194Trp were associated with arsenic-related urinary TCC and the interaction between the genotype and the exposure was statistically significant. The modulating effect of the GSTM1, GSTT1, GSTP1 Ile105Val, EPHX Tyr113His and XRCC1 Arg280His on arsenic-related TCC risk was also suggestive. These observations implied that impaired metabolism of carcinogenic exposure as well as impaired DNA repair function play an important role in arsenic-related urinary transitional cell carcinogenesis.
SDGs
Other Subjects
arginine; arsenic; epoxide hydrolase; glutathione transferase M1; glutathione transferase P1; glutathione transferase T1; isoleucine; tryptophan; valine; well water; XRCC1 protein; adult; age distribution; aged; amino acid substitution; article; cancer risk; cancer susceptibility; carcinogenesis; cigarette smoking; controlled study; female; genotype; human; major clinical study; male; onset age; outpatient; sex difference; single nucleotide polymorphism; Taiwan; transitional cell carcinoma; urinary tract cancer; Adult; Aged; Arsenic; Carcinoma, Transitional Cell; Case-Control Studies; DNA-Binding Proteins; Environmental Exposure; Epoxide Hydrolases; Female; Genetic Predisposition to Disease; Glutathione S-Transferase pi; Glutathione Transferase; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Polymorphism, Single Nucleotide; Risk Factors; Taiwan; Urologic Neoplasms; Water Pollutants, Chemical
Type
journal article