title: Risk of renal cell carcinoma and polymorphism in phase I xenobiotic metabolizing CYP1A1 and CYP2D6 enzymes.
abstract: The progressive increase in sporadic renal cell carcinoma (RCC) observed in industrialized countries supports the opinion that certain carcinogens present in the environment (tobacco smoke, drugs, pollutants, and dietary constituents) may affect the occurrence and progression of this disease in developing countries like India. The polymorphism of the enzymes involved in metabolism of such environmental factors may, therefore, confer variable propensity to RCC. The possible association between RCC and a polymorphism of the CYP1A1 and CYP2D6 genes specific to the Indian population was examined using peripheral blood DNA from 196 RCC cases and 250 population controls with detailed data of clinicopathologic characteristics for the disease. The CYP1A1 (val) "variant" genotype, which contains at least 1 copy of the CYP1A1 variant alleles, was found to be associated with a 2.03-fold [GG ver. AA/AG, unadjusted OR = 2.03; 95%CI = 1.233-3.342; P = 0.005] increase in the risk of RCC. There was also a significant association (p(trend) = 0.034) between higher frequency of RCC subjects containing at least of copy of the CYP1A1 (val) "variant" genotype with III or IV Fuhrman's grade. Whereas, the CYP2D6 polymorphism did not show any association with RCC risk [TT ver. CT/CC, unadjusted OR = 95%CI = 1.233-3.342; P = 0.005]. There was a significant association (p(trend) = 0.001) between the poor metabolizer CYP2D6 (TT) and progression towards higher pathological stage of RCC. Our data demonstrate for the first time a significant association between pharmacogenetic polymorphisms of CYP1A1 and risk of RCC development in the Indian population. The findings suggest that inter-individual variation in the phase I metabolic enzymes involved in the fictionalization and detoxification of specific xenobiotics is an important susceptibility factor for development and progression of RCC in Indians.
authors.affiliation: Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, India.
authors.forename: Shiekh Tanveer
authors.initials: ST
authors.lastname: Ahmad
authors.forename: Wani
authors.initials: W
authors.lastname: Arjumand
authors.forename: Amlesh
authors.initials: A
authors.lastname: Seth
authors.forename: Sana
authors.initials: S
authors.lastname: Nafees
authors.forename: Summya
authors.initials: S
authors.lastname: Rashid
authors.forename: Nemat
authors.initials: N
authors.lastname: Ali
authors.forename: Oday O
authors.initials: OO
authors.lastname: Hamiza
authors.forename: Sarwat
authors.initials: S
authors.lastname: Sultana
mesh_terms: D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D050216:Metabolic Detoxication, Phase I; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D015262:Xenobiotics; D019363:Cytochrome P-450 CYP1A1; D019389:Cytochrome P-450 CYP2D6