Journal Article

Associations between <i>NBS1</i> polymorphisms, haplotypes and smoking-related cancers

Sungshim L. Park, Delara Bastani, Binh Y. Goldstein, Shen-Chih Chang, Wendy Cozen, Lin Cai, Carlos Cordon-Cardo, Baoguo Ding, Sander Greenland, Na He, Shehnaz K. Hussain, Qingwu Jiang, Yuan-Chin A. Lee, Simin Liu, Ming-Lan Lu, Thomas M. Mack, Jenny T. Mao, Hal Morgenstern, Li-Na Mu, Sam S. Oh, Allan Pantuck, Jeanette C. Papp, Jianyu Rao, Victor E. Reuter, Donald P. Tashkin, Hua Wang, Nai-Chieh Y. You, Shun-Zhang Yu, Jin-Kou Zhao and Zuo-Feng Zhang

in Carcinogenesis

Volume 31, issue 7, pages 1264-1271
Published in print July 2010 | ISSN: 0143-3334
Published online May 2010 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgq096
Associations between NBS1 polymorphisms, haplotypes and smoking-related cancers

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Constituents of tobacco smoke can cause DNA double-strand breaks (DSBs), leading to tumorigenesis. The NBS1 gene product is a vital component in DSB detection and repair, thus genetic variations may influence cancer development. We examined the associations between NBS1 polymorphisms and haplotypes and newly incident smoking-related cancers in three case–control studies (Los Angeles: 611 lung and 601 upper aero-digestive tract (UADT) cancer cases and 1040 controls; Memorial Sloan-Kettering Cancer Center: 227 bladder cancer cases and 211 controls and Taixing, China: 218 esophagus, 206 stomach, 204 liver cancer cases and 415 controls). rs1061302 was associated with cancers of the lung [adjusted odds ratio (ORadj) = 1.6, 95% confidence interval (CI): 1.2, 2.4], larynx (ORadj = 0.56, 95% CI: 0.32, 0.97) and liver (ORadj = 1.7, 95% CI: 1.0, 2.9). Additionally, positive associations were found for rs709816 with bladder cancer (ORadj = 4.2, 95% CI: 1.4, 12) and rs1063054 with lung cancer (ORadj = 1.6, 95% CI: 1.0, 2.3). Some associations in lung and stomach cancers varied with smoking status. CAC haplotype was positively associated with smoking-related cancers: lung (ORadj = 1.7, 95% CI: 1.1, 2.9) and UADT (ORadj = 2.0, 95% CI: 1.1, 3.7), specifically, oropharynx (ORadj = 2.1, 95% CI: 1.0, 4.2) and larynx (ORadj = 4.8, 95% CI: 1.7, 14). Bayesian false-discovery probabilities were calculated to assess Type I error. It appears that NBS1 polymorphisms and haplotypes may be associated with smoking-related cancers and that these associations may differ by smoking status. Our findings also suggest that single-nucleotide polymorphisms located in the binding region of the MRE-RAD50-NBS1 complex or microRNA targeted pathways may influence tumor development. These hypotheses should be further examined in functional studies.

Journal Article.  5697 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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