title: Polymorphisms in DNA repair and metabolic genes in bladder cancer.
abstract: We investigated the association of urinary bladder cancer with genetic polymorphisms in the xeroderma pigmentosum complementation group C (XPC), group D (XPD) and group G (XPG), X-ray repair cross-complementing group 1 (XRCC1) and group 3 (XRCC3), Nijmegen breakage syndrome 1 (NBS1), cyclin D1, methylene-tetrahydrofolate reductase (MTHFR), NAD(P)H dehydrogenase quinone 1 (NQO1), H-ras and glutathione S-transferase theta 1 (GSTT1) genes. Bladder cancer patients from the different hospitals in Stockholm County Council area and matching controls were genotyped for different polymorphisms. The frequency of the variant allele for A/C polymorphism in exon 15 of the XPC gene was significantly higher in the bladder cancer cases than in the controls (OR 1.49, 95% CI 1.16-1.92, P = 0.001). The variant allele homozygote genotype for the T/C polymorphism in exon 1 of the H-ras gene was associated with a decreased risk for bladder cancer (OR 0.12, 95% CI 0.02-0.67, P = 0.006). The variant allele genotypes for the single nucleotide polymorphisms (SNPs) in DNA repair genes, XPG and NBS1, showed a marginal association with the occurrence of bladder cancer (OR 0.38, 95% CI 0.15-0.94, P = 0.03 and OR 1.64, 95% CI 0.92-2.90, P = 0.09, respectively). We also report a positive correlation between the null homozygote of GSTT1 with the risk of bladder cancer (OR 2.54, 95% CI 1.32-4.98, P = 0.003). For other polymorphisms included in this study, NBS1 Glu185Gln, XPD Lys751Gln, XPG Asp1104His, XRCC1 Arg399Gln, XRCC3 Thr241Met, cyclin D1 Pro242Pro, MTHFR Ala222Val and Glu429Ala, NQO1 Arg139Trp and Pro187Ser, no significant differences for genotype distributions and allele frequencies between the bladder cancer cases and the controls were observed in the present study.
authors.affiliation: Department of Biosciences at Novum, Karolinska Institute, S-14157 Huddinge, Sweden.
authors.forename: Somali
authors.initials: S
authors.lastname: Sanyal
authors.forename: Fabiola
authors.initials: F
authors.lastname: Festa
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sakano
authors.forename: Zhengzhong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Gunnar
authors.initials: G
authors.lastname: Steineck
authors.forename: Ulf
authors.initials: U
authors.lastname: Norming
authors.forename: Hans
authors.initials: H
authors.lastname: Wijkström
authors.forename: Per
authors.initials: P
authors.lastname: Larsson
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics; D004260:DNA Repair; D005787:Gene Frequency; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase