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- Title
Associations between NBS1 polymorphisms, haplotypes and smoking-related cancers.
- Authors
Park, Sungshim L.; Bastani, Delara; Goldstein, Binh Y.; Shen-Chih Chang; Cozen, Wendy; Cai, Lin; Cordon-Cardo, Carlos; Ding, Baoguo; Greenland, Sander; Na He; Hussain, Shehnaz K.; Qingwu Jiang; Lee, Yuan-Chin A.; Liu, Simin; Ming-Lan Lu; Mack, Thomas M.; Mao, Jenny T.; Morgenstern, Hal; Li-Na Mu; Oh, Sam S.
- Abstract
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.
- Subjects
TOBACCO smoke; CARCINOGENESIS; CANCER genetics; ESOPHAGEAL cancer; BLADDER
- Publication
Carcinogenesis, 2010, Vol 31, Issue 7, p1264
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgq096