TY - JOUR
T1 - Associations between NBS1 polymorphisms, haplotypes and smoking-related cancers
AU - Park, Sungshim L.
AU - Bastani, Delara
AU - Goldstein, Binh Y.
AU - Chang, Shen Chih
AU - Cozen, Wendy
AU - Cai, Lin
AU - Cordon-Cardo, Carlos
AU - Ding, Baoguo
AU - Greenland, Sander
AU - He, Na
AU - Hussain, Shehnaz K.
AU - Jiang, Qingwu
AU - Lee, Yuan Chin A.
AU - Liu, Simin
AU - Lu, Ming Lan
AU - Mack, Thomas M.
AU - Mao, Jenny T.
AU - Morgenstern, Hal
AU - Mu, Li Na
AU - Oh, Sam S.
AU - Pantuck, Allan
AU - Papp, Jeanette C.
AU - Rao, Jianyu
AU - Reuter, Victor E.
AU - Tashkin, Donald P.
AU - Wang, Hua
AU - You, Nai Chieh Y.
AU - Yu, Shun Zhang
AU - Zhao, Jin Kou
AU - Zhang, Zuo Feng
N1 - Funding Information:
National Institutes of Health (ES06718, ES01167, CA90833, CA077954, CA09142, CA96134, DA11386); Seymour Family Gift for Innovative Investigator-Initiated Research in Bladder Cancer; Alper Research Center for Environmental Genomics of the University of California, Los Angeles Jonsson Comprehensive Cancer Center.
PY - 2010/5/17
Y1 - 2010/5/17
N2 - 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 falsediscovery 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.
AB - 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 falsediscovery 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.
UR - https://www.scopus.com/pages/publications/77954355121
U2 - 10.1093/carcin/bgq096
DO - 10.1093/carcin/bgq096
M3 - Article
C2 - 20478923
AN - SCOPUS:77954355121
SN - 0143-3334
VL - 31
SP - 1264
EP - 1271
JO - Carcinogenesis
JF - Carcinogenesis
IS - 7
ER -