Polymorphisms in genes related to activation or detoxification of carcinogens might interact with smoking to increase renal cancer risk: Results from The Netherlands Cohort Study on diet and cancer
article
Metabolic gene polymorphisms have previously been suggested as risk factors for renal cell carcinoma (RCC). These polymorphisms are involved in activation or detoxification of carcinogens in cigarette smoke which is another RCC risk factor. We evaluated gene-environment interactions between CYP1A1, GSTμ1 and smoking in a large population-based RCC case group. The Netherlands Cohort Study on diet and cancer (NLCS) comprises 120,852 persons who completed a questionnaire on smoking and other risk factors at baseline. After 11.3 years of follow-up, 337 incident RCC cases were identified. DNA was collected for 245 cases. In a case-only analysis, interaction-odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using logistic regression. We observed a moderate, not statistically significant, interaction between current smoking and CYP1A1*2C (OR 1.42; 95% CI 0.70-2.89) and GSTμ1 null (OR 1.35; 95% CI 0.65-2.79). For current smokers with both a variant (heterozygous or homozygous) in CYP1A1 and GSTμ1 null, risk was also increased (OR 1.63; 95% CI 0.63-4.24). No interaction was observed between ever smokers, smoking duration (increments of 10 smoking years) or amount (increments of 5 cigarettes/day) and CYP1A or GSTμ1. Our results show a modest trend towards a statistically significant gene-environment interaction between CYP1A1, GSTμ1 and smoking in RCC. This could indicate that RCC risk among smokers might be more increased with the CYP1A1*2C genotype, GSTμ1 null, or both a CYP1A1 variant and GSTμ1 null. © Springer-Verlag 2007.
Topics
Leefomgeving en gezondheidCYP1A1 genotypeGene-environment interactionGSTμ1 genotypeRenal cell cancerSmokingcarcinogencytochrome P450 1A1DNAglutathione S-transferase M1glutathione transferaseglutathione transferase M1agar gel electrophoresisagedarticlebiotransformationcomparative studyfemalefollow upgenetic polymorphismgeneticsgenotypehumanincidencekidney carcinomakidney tumormalemiddle agedNetherlandspolymerase chain reactionprospective studyrisk factorsmokingAgedBiotransformationCarcinogensCarcinoma, Renal CellCytochrome P-450 CYP1A1DNA, NeoplasmElectrophoresis, Agar GelFemaleFollow-Up StudiesGenotypeGlutathione TransferaseHumansIncidenceKidney NeoplasmsMaleMiddle AgedNetherlandsPolymerase Chain ReactionPolymorphism, GeneticProspective StudiesRisk FactorsSmoking
TNO Identifier
240647
ISSN
07244983
Source
World Journal of Urology, 26(1), pp. 103-110.
Pages
103-110
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