title: Genetic variation in the base excision repair pathway and bladder cancer risk.
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-beta (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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, Bethesda, MD, USA. figueroaj@mail.nih.gov
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
authors.forename: Núria
authors.initials: N
authors.lastname: Malats
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Real
authors.forename: Debra
authors.initials: D
authors.lastname: Silverman
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Robert
authors.initials: R
authors.lastname: Welch
authors.forename: Mustafa
authors.initials: M
authors.lastname: Dosemeci
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardón
authors.forename: Consol
authors.initials: C
authors.lastname: Serra
authors.forename: Alfredo
authors.initials: A
authors.lastname: Carrato
authors.forename: Reina
authors.initials: R
authors.lastname: García-Closas
authors.forename: Gemma
authors.initials: G
authors.lastname: Castaño-Vinyals
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Montserrat
authors.initials: M
authors.lastname: García-Closas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D001749:Urinary Bladder Neoplasms / Q000235:genetics*