ABSTRACT
Numerous enzymes, including Cytochrome P450s (phase I) and Glutathione-S-transferases (phase II), are involved in the metabolic activation and detoxification of carcinogens. Epidemiological studies have consistently demonstrated that bladder cancer is strongly associated with cigarette smoking, and the risk for the development of this neoplasia may be modified by individual differences in carcinogen-metabolizing genes. We investigated the relationship between polymorphisms in the CYP1A1, GSTM1, GSTT1, and GSTP1 genes in a case-control study with 100 bladder cancer patients and 100 controls matched for age, gender, race, and smoking status. The GSTM1, GSTT1, CYP1A1 (A2455-->G), and GSTP1 (A313-->G) genotypes were determined using a multiplex PCR, an allele specific PCR, and a restriction fragment length polymorphism-PCR method. The present case-controlled association study did not detect any positive or negative association for the GSTM1 and GSTP1 genes [odds ratios (OR) = 1.35; 95% confidence interval (CI) = 0.76-2.41 and OR = 0.75; 95% CI = 0.41-1.38, respectively]. Notably, the genes GSTT1 and CYP1A1 exhibited a statistically significant association with bladder cancer (OR = 1.77; 95% CI = 1.01-3.12 and OR = 1.99; 95% CI = 1.07-3.73). No differences for GSTM1 and GSTP1 genotype prevalence between the bladder cancer cases and the controls were observed, however, the null genotype for the GSTT1 gene and the A/G and G/G variants of the CYP1A1 gene may contribute to the development of bladder cancer.
Subject(s)
Cytochrome P-450 CYP1A1/genetics , Glutathione S-Transferase pi/genetics , Glutathione Transferase/genetics , Urinary Bladder Neoplasms/genetics , Aged , Aged, 80 and over , Case-Control Studies , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment LengthABSTRACT
BACKGROUND: A case control association study was carried out to investigate polymorphisms in genes CYP1A1 (3801T > C), GSTM1, and GSTT1 (null genotypes) and oral squamous cell carcinoma (OSCC), including a correlation with some histopathological findings (tumor size, lymph node invasion and degree of tumor differentiation). PATIENTS AND METHODS: The patients (n = 91) and the controls (n = 81) were matched by age, sex, ethnicity and smoking habits. The molecular analysis was carried out using Polymerase Chain Reaction-Restrict Length Polymorphisms PCR-RFLP (CYP1A1) and Multiplex-PCR (GSTM1/GSTT1). RESULTS: No association was found for any of the studied genes: CYP1A1 (odds ratio (OR) = 1.24; 95% Confidence Interval (CI) = 0.67-2.31), GSTM1 (OR = 0.61; CI 95% = 0.33-1.11), and GSTT1 (OR = 1.24; CI 95% = 0.65-2.38). The analysis of combining genotypes also showed lack of association. Comparison with the histopathological findings did not, in general, detect any statistically significant differences. CONCLUSION: CYP1A1, GSTM1 and GSTT1 polymorphisms do not appear to influence the genetic susceptibility to OSCC or the progression to more advanced stages.
