Genetic variation in the base excision repair pathway and bladder cancer risk

Jonine D. Figueroa, Núria Malats, Francisco X. Real, Debra Silverman, Manolis Kogevinas, Stephen Chanock, Robert Welch, Mustafa Dosemeci, Adonina Tardón, Consol Serra, Alfredo Carrato, Montserrat García-Closas, Gemma Castaño-Vinyals, Nathaniel Rothman, Reina García-Closas

Research output: Contribution to journalArticle

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-(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 PARP1rs1136410 (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.

Original languageEnglish (US)
Pages (from-to)233-242
Number of pages10
JournalHuman Genetics
Volume121
Issue number2
DOIs
Publication statusPublished - Apr 2007
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Figueroa, J. D., Malats, N., Real, F. X., Silverman, D., Kogevinas, M., Chanock, S., ... García-Closas, R. (2007). Genetic variation in the base excision repair pathway and bladder cancer risk. Human Genetics, 121(2), 233-242. https://doi.org/10.1007/s00439-006-0294-y