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

• Published in: Human genetics Vol. 121; no. 2; pp. 233 - 242
• Main Authors: Figueroa, Jonine D., Malats, Núria, Real, Francisco X., Silverman, Debra, Kogevinas, Manolis, Chanock, Stephen, Welch, Robert, Dosemeci, Mustafa, Tardón, Adonina, Serra, Consol, Carrato, Alfredo, García-Closas, Reina, Castaño-Vinyals, Gemma, Rothman, Nathaniel, García-Closas, Montserrat
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.04.2007; Berlin Springer Nature B.V; New York, NY
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Bladder cancer; Cancer; Classical genetics, quantitative genetics, hybrids; DNA Damage; DNA Repair; Female; Fundamental and applied biological sciences. Psychology; Genes; Genetic aspects; Genetic Predisposition to Disease; Genetic research; Genetic Variation; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Health aspects; Human; Humans; Male; Medical sciences; Middle Aged; Monosaccharides; Nephrology. Urinary tract diseases; Oncology, Experimental; Polymorphism, Genetic; Risk; Risk factors; Single nucleotide polymorphisms; Sugars; Tumors of the urinary system; Urinary Bladder Neoplasms - genetics; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; Urinary system disease; Genetic variability; Excision; Genetic variant; Genetics; Risk; Bladder disease; Malignant tumor; Urinary tract disease; Repair; Bladder cancer
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-006-0294-y

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.