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

de Verdier, Petra J.; Sanyal, Somali; Bermejo, Justo Lorenzo; Steineck, Gunnar; Hemminki, Kari LU and Kumar, Rajiv (2010) In Mutation Research 694(1-2). p.39-44
Abstract
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... (More)
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 (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
Urinary bladder cancer, Haplotypes, Polymorphisms, XPC
in
Mutation Research
volume
694
issue
1-2
pages
39 - 44
publisher
Elsevier
external identifiers
  • wos:000285667900006
  • scopus:78649451471
ISSN
1873-135X
DOI
10.1016/j.mrfmmm.2010.09.003
language
English
LU publication?
yes
id
508cefaf-e460-49b6-871c-e95669028f25 (old id 1815198)
date added to LUP
2011-03-02 12:45:55
date last changed
2018-05-29 09:20:41
@article{508cefaf-e460-49b6-871c-e95669028f25,
  abstract     = {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&gt;T) K939Q (A&gt;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&gt;C) and PAT (-/+) polymorphisms and therefore only the K939Q (A&gt;C) polymorphism was included in analyses The over all estimated odds ratio was 1 7 (95% CI 1 3-2 4) for A499V (C&gt;T) and 1 4 (95% CI 1 0-2 0) for K939Q (A&gt;C) The associated odds ratio Increase with the variant allele homozygotes was six-fold for the A499V (C&gt;T) and three-fold for the K939Q (A&gt;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&lt;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},
  author       = {de Verdier, Petra J. and Sanyal, Somali and Bermejo, Justo Lorenzo and Steineck, Gunnar and Hemminki, Kari and Kumar, Rajiv},
  issn         = {1873-135X},
  keyword      = {Urinary bladder cancer,Haplotypes,Polymorphisms,XPC},
  language     = {eng},
  number       = {1-2},
  pages        = {39--44},
  publisher    = {Elsevier},
  series       = {Mutation Research},
  title        = {Genotypes, haplotypes and diplotypes of three XPC polymorphisms in urinary-bladder cancer patients},
  url          = {http://dx.doi.org/10.1016/j.mrfmmm.2010.09.003},
  volume       = {694},
  year         = {2010},
}