Xenobiotic Metabolizing Gene Variants and Renal Cell Cancer: A Multicenter Study

Background: The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer (RCC). Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. Methods: The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case–control study conducted between 1998 and 2003 across seven centers in Central and Eastern Europe. Detailed data were collected from 874 cases and 2053 controls on demographics, work history, and occupational exposure to chemical agents. Genes [cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT), uridine diphosphate-glucuronosyltransferase (UGT)] were selected for the present analysis based on their putative role in xenobiotic metabolism. Haplotypes were calculated using fastPhase. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for country of residence, age, sex, smoking, alcohol intake, obesity, and hypertension. Results: We observed an increased risk of RCC with one SNP. After adjustment for multiple comparisons it did not remain significant. Neither NAT1 nor NAT2 slow acetylation was associated with disease. Conclusion: We observed no association between this pathway and renal cell cancer

Polymorphisms in Th1/Th2 cytokine Genes, hormone replacement therapy, and risk of non-Hodgkin lymphoma

AbstractWe conducted a population-based case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the relationship between hormone replacement therapy (HRT) and risk of non-Hodgkin lymphoma (NHL). Compared to women without a history of HRT use, women with a history of HRT use had a significantly decreased risk of NHL if they carried IFNGR2 (rs1059293) CT/TT genotypes (OR=0.5, 95%CI: 0.3-0.9), IL13 (rs20541) GG genotype (OR=0.6, 95%CI: 0.4-0.9) and IL13 (rs1295686) CC genotype (OR=0.6, 95%CI: 0.4-0.8), but not among women who carried IFNGR2 CC, IL13 AG /AA and IL13 CT/TT genotypes. A similar pattern was also observed for B-cell lymphoma but not for T-cell lymphoma. A statistically significant interaction was observed for IFNGR2 (rs1059293 Pforinteraction=0.024), IL13 (rs20541 Pforinteraction=0.005), IL13 (rs1295686 Pforinteraction=0.008) and IL15RA (rs2296135 Pforinteraction=0.049) for NHL overall; IL13 (rs20541 Pforinteraction=0.0009), IL13 (rs1295686 Pforinteraction=0.0002), and IL15RA (rs2296135 Pforinteraction=0.041) for B-cell lymphoma. The results suggest that common genetic variation in Th1/Th2 pathway genes may modify the association between HRT and NHL risk