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Analysis of variants in DNA damage signalling genes in bladder cancer

BACKGROUND: Chemicals from occupational exposure and components of cigarette smoke can cause DNA damage in bladder urothelium. Failure to repair DNA damage by DNA repair proteins may result in mutations leading to genetic instability and the development of bladder cancer. Immunohistochemistry studie...

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Autores principales: Choudhury, Ananya, Elliott, Faye, Iles, Mark M, Churchman, Michael, Bristow, Robert G, Bishop, D Timothy, Kiltie, Anne E
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2488326/
https://www.ncbi.nlm.nih.gov/pubmed/18638378
http://dx.doi.org/10.1186/1471-2350-9-69
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author Choudhury, Ananya
Elliott, Faye
Iles, Mark M
Churchman, Michael
Bristow, Robert G
Bishop, D Timothy
Kiltie, Anne E
author_facet Choudhury, Ananya
Elliott, Faye
Iles, Mark M
Churchman, Michael
Bristow, Robert G
Bishop, D Timothy
Kiltie, Anne E
author_sort Choudhury, Ananya
collection PubMed
description BACKGROUND: Chemicals from occupational exposure and components of cigarette smoke can cause DNA damage in bladder urothelium. Failure to repair DNA damage by DNA repair proteins may result in mutations leading to genetic instability and the development of bladder cancer. Immunohistochemistry studies have shown DNA damage signal activation in precancerous bladder lesions which is lost on progression, suggesting that the damage signalling mechanism acts as a brake to further tumorigenesis. Single nucleotide polymorphisms (SNPs) in DSB signalling genes may alter protein function. We hypothesized that SNPs in DSB signalling genes may modulate predisposition to bladder cancer and influence the effects of environmental exposures. METHODS: We recruited 771 cases and 800 controls (573 hospital-based and 227 population-based from a previous case-control study) and interviewed them regarding their smoking habits and occupational history. DNA was extracted from a peripheral blood sample and genotyping of 24 SNPs in MRE11, NBS1, RAD50, H2AX and ATM was undertaken using an allelic discrimination method (Taqman). RESULTS: Smoking and occupational dye exposure were strongly associated with bladder cancer risk. Using logistic regression adjusting for age, sex, smoking and occupational dye exposure, there was a marginal increase in risk of bladder cancer for an MRE11 3'UTR SNP (rs2155209, adjusted odds ratio 1.54 95% CI (1.13–2.08, p = 0.01) for individuals homozygous for the rare allele compared to those carrying the common homozygous or heterozygous genotype). However, in the hospital-based controls, the genotype distribution for this SNP deviated from Hardy-Weinberg equilibrium. None of the other SNPs showed an association with bladder cancer and we did not find any significant interaction between any of these polymorphisms and exposure to smoking or dye exposure. CONCLUSION: Apart from a possible effect for one MRE11 3'UTR SNP, our study does not support the hypothesis that SNPs in DSB signaling genes modulate predisposition to bladder cancer.
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spelling pubmed-24883262008-07-29 Analysis of variants in DNA damage signalling genes in bladder cancer Choudhury, Ananya Elliott, Faye Iles, Mark M Churchman, Michael Bristow, Robert G Bishop, D Timothy Kiltie, Anne E BMC Med Genet Research Article BACKGROUND: Chemicals from occupational exposure and components of cigarette smoke can cause DNA damage in bladder urothelium. Failure to repair DNA damage by DNA repair proteins may result in mutations leading to genetic instability and the development of bladder cancer. Immunohistochemistry studies have shown DNA damage signal activation in precancerous bladder lesions which is lost on progression, suggesting that the damage signalling mechanism acts as a brake to further tumorigenesis. Single nucleotide polymorphisms (SNPs) in DSB signalling genes may alter protein function. We hypothesized that SNPs in DSB signalling genes may modulate predisposition to bladder cancer and influence the effects of environmental exposures. METHODS: We recruited 771 cases and 800 controls (573 hospital-based and 227 population-based from a previous case-control study) and interviewed them regarding their smoking habits and occupational history. DNA was extracted from a peripheral blood sample and genotyping of 24 SNPs in MRE11, NBS1, RAD50, H2AX and ATM was undertaken using an allelic discrimination method (Taqman). RESULTS: Smoking and occupational dye exposure were strongly associated with bladder cancer risk. Using logistic regression adjusting for age, sex, smoking and occupational dye exposure, there was a marginal increase in risk of bladder cancer for an MRE11 3'UTR SNP (rs2155209, adjusted odds ratio 1.54 95% CI (1.13–2.08, p = 0.01) for individuals homozygous for the rare allele compared to those carrying the common homozygous or heterozygous genotype). However, in the hospital-based controls, the genotype distribution for this SNP deviated from Hardy-Weinberg equilibrium. None of the other SNPs showed an association with bladder cancer and we did not find any significant interaction between any of these polymorphisms and exposure to smoking or dye exposure. CONCLUSION: Apart from a possible effect for one MRE11 3'UTR SNP, our study does not support the hypothesis that SNPs in DSB signaling genes modulate predisposition to bladder cancer. BioMed Central 2008-07-18 /pmc/articles/PMC2488326/ /pubmed/18638378 http://dx.doi.org/10.1186/1471-2350-9-69 Text en Copyright © 2008 Choudhury et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Choudhury, Ananya
Elliott, Faye
Iles, Mark M
Churchman, Michael
Bristow, Robert G
Bishop, D Timothy
Kiltie, Anne E
Analysis of variants in DNA damage signalling genes in bladder cancer
title Analysis of variants in DNA damage signalling genes in bladder cancer
title_full Analysis of variants in DNA damage signalling genes in bladder cancer
title_fullStr Analysis of variants in DNA damage signalling genes in bladder cancer
title_full_unstemmed Analysis of variants in DNA damage signalling genes in bladder cancer
title_short Analysis of variants in DNA damage signalling genes in bladder cancer
title_sort analysis of variants in dna damage signalling genes in bladder cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2488326/
https://www.ncbi.nlm.nih.gov/pubmed/18638378
http://dx.doi.org/10.1186/1471-2350-9-69
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