title: Cytochrome P450 1B1 polymorphisms and risk of renal cell carcinoma in men.
abstract: The cytochrome P450 1B1 (CYP1B1) enzyme activates xenobiotics to reactive forms as well as convert estradiol to 4-hydroxy-estradiol that has been shown to play a role in the carcinogenesis process of the kidney in male but not female animals. Prior reports show polymorphic variants of CYP1B1 to alter catalytic activity, and thus, we hypothesize that polymorphisms of the CYP1B1 gene are involved in the malignant transformation of the renal cell in men. The genetic distributions of five CYP1B1 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism in 480 normal healthy subjects and 403 sporadic renal cell carcinoma cases. All subjects were Caucasian men. The sites evaluated were codons 48 (C → G, Arg → Gly, rs10012), 119 (G → T, Ala → Ser, rs1056827), 432 (C → G, Leu → Val, rs1056836), 449 (C → T, Asp, rs1056837), and 453 (A → G, Asn → Ser, rs1800440). A trend was demonstrated for the 432 Val/Val (χ2, P = 0.06) and 449 T/T (χ2, P = 0.1) genotypes to play a protective role against renal cancer. Odds ratio (95 % confidence interval) for Val/Val compared to Leu/Leu at codon 432 was 0.65 (0.44-0.95) and T/T compared to C/C at codon 449 was 0.67 (0.45-0.99). Codons 432 and 449 were observed to be linked (D = 0.24), and haplotype involving 432 Val and 449 T was significantly reduced in cancer cases (P = 0.04). No association was found, however, when analyzing polymorphic sites with clinical stage of cancer. These results demonstrate polymorphisms of CYP1B1 to be associated with renal carcinogenesis and are of importance in understanding their role in the pathogenesis of renal cell carcinoma.
authors.affiliation: Department of Oral Biology, College of Dentistry, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea, ichang@yuhs.ac.
authors.forename: Inik
authors.initials: I
authors.lastname: Chang
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Fukuhara
authors.forename: Darryn K
authors.initials: DK
authors.lastname: Wong
authors.forename: Ankurpreet
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authors.lastname: Gill
authors.forename: Yozo
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authors.lastname: Mitsui
authors.forename: Shahana
authors.initials: S
authors.lastname: Majid
authors.forename: Sharanjot
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authors.lastname: Saini
authors.forename: Soichiro
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authors.lastname: Yamamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Chiyomaru
authors.forename: Hiroshi
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authors.lastname: Hirata
authors.forename: Koji
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authors.lastname: Ueno
authors.forename: Sumit
authors.initials: S
authors.lastname: Arora
authors.forename: Varahram
authors.initials: V
authors.lastname: Shahryari
authors.forename: Guoren
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authors.lastname: Deng
authors.forename: Z Laura
authors.initials: ZL
authors.lastname: Tabatabai
authors.forename: Kirsten L
authors.initials: KL
authors.lastname: Greene
authors.forename: Dong Min
authors.initials: DM
authors.lastname: Shin
authors.forename: Hideki
authors.initials: H
authors.lastname: Enokida
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shiina
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
authors.forename: Rajvir
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authors.lastname: Dahiya
authors.forename: Yuichiro
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authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1