Journal Article

Polymorphisms in DNA repair and metabolic genes in bladder cancer

Somali Sanyal, Fabiola Festa, Shigeru Sakano, Zhengzhong Zhang, Gunnar Steineck, Ulf Norming, Hans Wijkström, Per Larsson, Rajiv Kumar and Kari Hemminki

in Carcinogenesis

Volume 25, issue 5, pages 729-734
Published in print May 2004 | ISSN: 0143-3334
Published online May 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh058
Polymorphisms in DNA repair and metabolic genes in bladder cancer

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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.

Keywords: GSTT1, glutathione S-transferase theta 1; MTHFR, methylene-tetrahydrofolate reductase; NBS1, Nijmegen breakage syndrome 1; NQO1, NAD(P)H dehydrogenase quinone 1; SNP, single nucleotide polymorphism; XPC, xeroderma pigmentosum complementation group C; XPD, xeroderma pigmentosum complementation group D; XPG, xeroderma pigmentosum complementation group G; XRCC1, X-ray repair cross-complementing group 1; XRCC3, X-ray repair cross-complementing group 3

Journal Article.  3948 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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