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

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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.

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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 Fernandez 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 efforts during field work. Lastly, Jonine Figueroa would like to thank the NCI cancer prevention fellowship program for their support.

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Correspondence to Jonine D. Figueroa.

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439_2006_294_MOESM1_ESM.doc

Supplementary Table 1: Association of 36 selected* polymorphisms in 12 base excision DNA repair genes on bladder cancer risk, adjusted for gender, age, region and smoking status (1,150 cases and 1,149 controls) (DOC 280 kb)

Appendix: Participating study centers in Spain

Appendix: Participating study centers in Spain

Institut Municipal d’Investigació Mèdica, Universitat Pompeu Fabra, Barcelona–Coordinating Center (M. Kogevinas, N. Malats, F.X. Real, F Fernandez, M. Sala, G. Castaño, M. Torà, D. Puente, C. Villanueva, C. Murta, J. Fortuny, E. López, S. Hernández, R. Jaramillo); Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona (J. Lloreta, S. Serrano, L. Ferrer, A. Gelabert, J. Carles, O. Bielsa, K. Villadiego), Hospital Germans Tries i Pujol, Badalona, Barcelona (L. Cecchini, J.M. Saladié, L. Ibarz); Hospital de Sant Boi, Sant Boi, Barcelona (M. Céspedes); Centre Hospitalari Parc Taulí, Sabadell, Barcelona (C. Serra, D. García, J. Pujadas, R. Hernando, A. Cabezuelo, C. Abad, A. Prera, J. Prat); ALTHAIA, Manresa, Barcelona (M. Domènech, J. Badal, J. Malet); Hospital Universitario, La Laguna, Tenerife (R. García-Closas, J. Rodríguez de Vera, A.I. Martín); Hospital La Candelaria, Santa Cruz, Tenerife (J. Taño, F. Cáceres); Hospital General Universitario de Elche, Universidad Miguel Hernández, Elche, Alicante (A. Carrato, F. García-López, M. Ull, A. Teruel, E. Andrada, A. Bustos, A. Castillejo, J.L. Soto); Universidad de Oviedo, Oviedo, Asturias (A. Tardón); Hospital San Agustín, Avilés, Asturias (J.L. Guate, J.M. Lanzas, J. Velasco); Hospital Central Covadonga, Oviedo, Asturias (J.M. Fernández, J.J. Rodríguez, A. Herrero), Hospital Central General, Oviedo, Asturias (R. Abascal, C. Manzano); Hospital de Cabueñes , Gijón, Asturias (M. Rivas, M. Arguelles); Hospital de Jove, Gijón, Asturias (M. Díaz, J. Sánchez, O. González); Hospital de Cruz Roja, Gijón, Asturias (A. Mateos, V. Frade); Hospital Alvarez-Buylla (Mieres, Asturias): P. Muntañola, C. Pravia; Hospital Jarrio, Coaña, Asturias (A.M. Huescar, F. Huergo); Hospital Carmen y Severo Ochoa, Cangas, Asturias (J. Mosquera).

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Figueroa, J.D., Malats, N., Real, F.X. et al. Genetic variation in the base excision repair pathway and bladder cancer risk. Hum Genet 121, 233–242 (2007). https://doi.org/10.1007/s00439-006-0294-y

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