title: Polymorphisms of catechol-O-methyltransferase in men with renal cell cancer.
abstract: The estrogen metabolite, 4-hydroxy-estrogen, has been shown to play a role in malignant transformation of male kidneys. To counteract the effects of this catechol-estrogen, the catechol-O-methyltransferase (COMT) enzyme is capable of neutralizing the genotoxic effects of this compound. A polymorphic variant of COMT has been shown to have a reduced enzyme activity, and thus, we hypothesize that single nucleotide polymorphisms of the COMT gene can be a risk factor for renal cell cancer (RCC). To determine this hypothesis, a study of a Japanese male population was used and the genetic distributions of COMT polymorphisms at codons 62 (C-->T), 72 (G-->T), and 158 (G-->A) were analyzed in 157 normal healthy subjects and 123 sporadic RCC (clear cell type) samples by using a sequence-specific PCR technique. These experiments show that the variant genotype (P = 0.025) and allele (P = 0.011) at codon 62 is a risk factor for RCC. The odds ratio and 95% confidence interval for cancer were 3.16 and 1.29 to 7.73, respectively, for the T/T genotype as compared with wild-type. No associations for renal cancer were found at either codons 72 or 158 in this Japanese male population. However, codons 62 and 158 were observed to be in linkage disequilibrium, and haplotype analysis shows the combined forms of T-A, T-G, and C-A to be associated with RCC as compared with C-G (P < 0.001). When evaluating the risk of COMT polymorphisms with grade of cancer, no associations were observed for any of the genotypes. This study is the first to report COMT polymorphism to be associated with RCC. These results are important in understanding the role of COMT polymorphisms in the pathogenesis of RCC.
authors.affiliation: Department of Urology, Veterans Affairs Medical Center and University of California at San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirata
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kikuno
authors.forename: Ken
authors.initials: K
authors.lastname: Kawamoto
authors.forename: Shahana
authors.initials: S
authors.lastname: Majid
authors.forename: Takashi
authors.initials: T
authors.lastname: Tokizane
authors.forename: Shinji
authors.initials: S
authors.lastname: Urakami
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shiina
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakajima
authors.forename: Rajiv
authors.initials: R
authors.lastname: Dhir
authors.forename: Rajvir
authors.initials: R
authors.lastname: Dahiya
mesh_terms: D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000453:epidemiology / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003062:Codon; D065633:Cytochrome P-450 CYP1B1; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007680:Kidney Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D003062:Codon; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D002394:Catechol O-Methyltransferase