Genotypes, haplotypes and diplotypes of three XPC polymorphisms in urinary-bladder cancer patients

• Purpose The XPC gene is involved in DNA damage recognition in the nucleotide excision repair pathway (NER) We investigated the additive effects of single nucleotide polymorphisms (SNPs) in bladder-cancer patients and population controls for three XPC polymorphisms A499V (C>T) K939Q (A>C) and poly AT (PAT -/+) Experimental Design 311 bladder-cancer patients from a population-based cohort and 337 population controls were genotyped using the PCR-restriction fragment length polymorphism (RFLP) technique Results We found complete linkage between the K939Q (A>C) and PAT (-/+) polymorphisms and therefore only the K939Q (A>C) polymorphism was included in analyses The over all estimated odds ratio was 1 7 (95% CI 1 3-2 4) for A499V (C>T) and 1 4 (95% CI 1 0-2 0) for K939Q (A>C) The associated odds ratio Increase with the variant allele homozygotes was six-fold for the A499V (C>T) and three-fold for the K939Q (A>C) polymorphism (OR=5 7 95% CI 3 4-9 5 and OR=2 6 95% CI 1 3-5 6 respectively) The variant allele haplotype of the two polymorphisms (T499C939) was associated with a nearly four fold increased odds ratio compared to the common allele haplotype (C(499)A(939)) (OR=3 6 95% Cl 1 9-6 9) Combined genotype analysis showed an Increased disease association with increasing number of variant alleles (p<0 0001) with a dominant effect of the A499V polymorphism In addition we observed association of the disease with increasing number of variant alleles for the A499V polymorphism and an early age at diagnosis (p=0 004) Conclusions Our results suggest an association between the XPC genotypes of the A499V K939Q and PAT polymorphisms and urinary-bladder cancer We propose a poly-allelic effect of these polymorphisms where the cumulative effect on disease becomes higher than the individual allelic effects (C) 2010 Elsevier B V All rights reserved

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Urinary bladder cancer

Haplotypes

Polymorphisms

XPC

XPC; Polymorphisms; Haplotypes; Urinary bladder cancer

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