title: 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.
abstract: 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, GSTmicro1 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 GSTmicro1 null (OR 1.35; 95% CI 0.65-2.79). For current smokers with both a variant (heterozygous or homozygous) in CYP1A1 and GSTmicro1 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 GSTmicro1. Our results show a modest trend towards a statistically significant gene-environment interaction between CYP1A1, GSTmicro1 and smoking in RCC. This could indicate that RCC risk among smokers might be more increased with the CYP1A1*2C genotype, GSTmicro1 null, or both a CYP1A1 variant and GSTmicro1 null.
authors.affiliation: Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. kim.smits@epid.unimaas.nl
authors.forename: Kim M
authors.initials: KM
authors.lastname: Smits
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Schouten
authors.forename: Boukje A C
authors.initials: BA
authors.lastname: van Dijk
authors.forename: Kjeld
authors.initials: K
authors.lastname: van Houwelingen
authors.forename: Christina A
authors.initials: CA
authors.lastname: Hulsbergen-van de Kaa
authors.forename: Lambertus A L M
authors.initials: LA
authors.lastname: Kiemeney
authors.forename: R Alexandra
authors.initials: RA
authors.lastname: Goldbohm
authors.forename: Egbert
authors.initials: E
authors.lastname: Oosterwijk
authors.forename: Piet A
authors.initials: PA
authors.lastname: van den Brandt
mesh_terms: D000368:Aged; D001711:Biotransformation / Q000235:genetics*; D002273:Carcinogens / Q000493:pharmacokinetics*; D002292:Carcinoma, Renal Cell / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004587:Electrophoresis, Agar Gel; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
chemical_list: D002273:Carcinogens; D019363:Cytochrome P-450 CYP1A1; D004273:DNA, Neoplasm; D005982:Glutathione Transferase