Polymorphisms in DNA repair genes, smoking, and bladder cancer risk: Findings from the International Consortium of Bladder Cancer

Mariana C. Stern, Jie Lin, Jonine D. Figueroa, Karl T. Kelsey, Anne E. Kiltie, Jian Min Yuan, Giuseppe Matullo, Tony Fletcher, Simone Benhamou, Jack A. Taylor, Donatella Placidi, Zuo Feng Zhang, Gunnar Steineck, Nathaniel Rothman, Manolis Kogevinas, Debra Silverman, Nuria Malats, Stephen Chanock, Xifeng Wu, Margaret R. KaragasAngeline S. Andrew, Heather H. Nelson, D. Timothy Bishop, Chung Sak Sei, Ananya Choudhury, Jennifer H. Barrett, Faye Elliot, Román Corral, Amit D. Joshi, Manuela Gago-Dominguez, Victoria K. Cortessis, Yong Bing Xiang, Yu Tang Gao, Paolo Vineis, Carlotta Sacerdote, Simonetta Guarrera, Silvia Polidoro, Alessandra Allione, Eugen Gurzau, Kvetoslava Koppova, Rajiv Kumar, Peter Rudnai, Stefano Porru, Angela Carta, Marcello Campagna, Cecilia Arici, Sung Shim Lani Park, Montserrat Garcia-Closas

Research output: Contribution to journalArticle

Abstract

Tobacco smoking is the most important and well-established bladder cancer risk factor and a rich source of chemical carcinogens and reactive oxygen species that can induce damage to DNA in urothelial cells. Therefore, common variation in DNA repair genes might modify bladder cancer risk. In this study, we present results from meta-analyses and pooled analyses conducted as part of the International Consortium of Bladder Cancer. We included data on 10 single nucleotide polymorphisms corresponding to seven DNA repair genes from 13 studies. Pooled analyses and meta-analyses included 5,282 cases and 5,954 controls of non-Latino white origin. We found evidence for weak but consistent associations with ERCC2 D312N [rs1799793; per-allele odds ratio (OR), 1.10; 95% confidence interval (95% CI), 1.01-1.19; P = 0.021], NBN E185Q (rs1805794; per-allele OR, 1.09; 95% CI, 1.01-1.18; P = 0.028), and XPC A499V (rs2228000; per-allele OR, 1.10; 95% CI, 1.00-1.21; P = 0.044). The association with NBN E185Q was limited to ever smokers (interaction P = 0.002) and was strongest for the highest levels of smoking dose and smoking duration. Overall, our study provides the strongest evidence to date for a role of common variants in DNA repair genes in bladder carcinogenesis.

Original languageEnglish (US)
Pages (from-to)6857-6864
Number of pages8
JournalCancer Research
Volume69
Issue number17
DOIs
StatePublished - Sep 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Stern, M. C., Lin, J., Figueroa, J. D., Kelsey, K. T., Kiltie, A. E., Yuan, J. M., Matullo, G., Fletcher, T., Benhamou, S., Taylor, J. A., Placidi, D., Zhang, Z. F., Steineck, G., Rothman, N., Kogevinas, M., Silverman, D., Malats, N., Chanock, S., Wu, X., ... Garcia-Closas, M. (2009). Polymorphisms in DNA repair genes, smoking, and bladder cancer risk: Findings from the International Consortium of Bladder Cancer. Cancer Research, 69(17), 6857-6864. https://doi.org/10.1158/0008-5472.CAN-09-1091