TY - JOUR
T1 - Genetic variation in the base excision repair pathway and bladder cancer risk
AU - Figueroa, Jonine D.
AU - Malats, Núria
AU - Real, Francisco X.
AU - Silverman, Debra
AU - Kogevinas, Manolis
AU - Chanock, Stephen
AU - Welch, Robert
AU - Dosemeci, Mustafa
AU - Tardón, Adonina
AU - Serra, Consol
AU - Carrato, Alfredo
AU - García-Closas, Montserrat
AU - Castaño-Vinyals, Gemma
AU - Rothman, Nathaniel
AU - García-Closas, Reina
N1 - Funding Information:
Acknowledgments This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and FIS/Spain grant numbers 00/0745, G03/174, G03/160, C03/09, C03/10. We thank Robert C. Saal from Westat, Rockville, MD, and Leslie Carroll and Jane Wang from IMS, Silver Spring, MD, for their support in study and data management; Doug Richesson from DCEG, NCI, for his support in data analysis, Dr. Maria Sala from IMIM, Barcelona, Spain, for her work in data collection; Francisco Fernan-dez for his work on data management, Dr. Montserrat Torà for her work in the coordination of sample collection and blood processing; and physicians, nurses, interviewers and study participants for their eVorts during Weld work. Lastly, Jonine Figueroa would like to thank the NCI cancer prevention fellowship program for their support.
PY - 2007/4
Y1 - 2007/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33947140923&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33947140923&partnerID=8YFLogxK
U2 - 10.1007/s00439-006-0294-y
DO - 10.1007/s00439-006-0294-y
M3 - Article
C2 - 17203305
AN - SCOPUS:33947140923
SN - 0340-6717
VL - 121
SP - 233
EP - 242
JO - Human genetics
JF - Human genetics
IS - 2
ER -