Genetic variation in the base excision repair pathway and bladder cancer risk |
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Authors: | Jonine D Figueroa Núria Malats Francisco X Real Debra Silverman Manolis Kogevinas Stephen Chanock Robert Welch Mustafa Dosemeci Adonina Tardón Consol Serra Alfredo Carrato Reina García-Closas Gemma Castaño-Vinyals Nathaniel Rothman Montserrat García-Closas |
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Institution: | (1) Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, Bethesda, MD, USA;(2) Institut Municipal d’Investigació Mèdica (IMIM), Center for Research in Environmental Epidemiology, Barcelona, Spain;(3) Universitat Pompeu Fabra, Barcelona, Spain;(4) Medical School, Heraklion, Greece;(5) Department of Health and Human Services, Core Genotype Facility at the Advanced Technology Center of the National Cancer Institute, Bethesda, MD, USA;(6) Universidad de Oviedo, Oviedo, Spain;(7) Hospital Universitario de Elche, Elche, Spain;(8) Unidad de Investigación, Hospital Universitario de Canarias, La Laguna, Spain |
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Abstract: | Genetic polymorphisms in DNA repair genes may impact individual variation in DNA repair capacity and alter cancer risk. In
order to examine the association of common genetic variation in the base-excision repair (BER) pathway with bladder cancer
risk, we analyzed 43 single nucleotide polymorphisms (SNPs) in 12 BER genes (OGG1, MUTYH, APEX1, PARP1, PARP3, PARP4, XRCC1, POLB, POLD1, PCNA, LIG1, and LIG3). Using genotype data from 1,150 cases of urinary bladder transitional cell carcinomas and 1,149 controls from the Spanish
Bladder Cancer Study we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, region and
smoking status. SNPs in three genes showed significant associations with bladder cancer risk: the 8-oxoG DNA glycosylase gene
(OGG1), the Poly (ADP-ribose) polymerase family member 1 (PARP1) and the major gap filling polymerase-β (POLB). Subjects who were heterozygous or homozygous variant for an OGG1 SNP in the promoter region (rs125701) had significantly decreased bladder cancer risk compared to common homozygous: OR (95%CI)
0.78 (0.63–0.96). Heterozygous or homozygous individuals for the functional SNP PARP1 rs1136410 (V762A) or for the intronic SNP POLB rs3136717 were at increased risk compared to those homozygous for the common alleles: 1.24 (1.02–1.51) and 1.30 (1.04–1.62),
respectively. In summary, data from this large case-control study suggested bladder cancer risk associations with selected
BER SNPs, which need to be confirmed in other study populations.
Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users. |
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