title: Associations between NBS1 polymorphisms, haplotypes and smoking-related cancers.
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 (OR(adj)) = 1.6, 95% confidence interval (CI): 1.2, 2.4], larynx (OR(adj) = 0.56, 95% CI: 0.32, 0.97) and liver (OR(adj) = 1.7, 95% CI: 1.0, 2.9). Additionally, positive associations were found for rs709816 with bladder cancer (OR(adj) = 4.2, 95% CI: 1.4, 12) and rs1063054 with lung cancer (OR(adj) = 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 (OR(adj) = 1.7, 95% CI: 1.1, 2.9) and UADT (OR(adj) = 2.0, 95% CI: 1.1, 3.7), specifically, oropharynx (OR(adj) = 2.1, 95% CI: 1.0, 4.2) and larynx (OR(adj) = 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.
authors.affiliation: Department of Epidemiology, School of Public Health, University of California, Los Angeles, 71-225 CHS, Box 951772, 650 Charles E Young Drive, South, Los Angeles, CA 90095-1772, USA.
authors.forename: Sungshim L
authors.initials: SL
authors.lastname: Park
authors.forename: Delara
authors.initials: D
authors.lastname: Bastani
authors.forename: Binh Y
authors.initials: BY
authors.lastname: Goldstein
authors.forename: Shen-Chih
authors.initials: SC
authors.lastname: Chang
authors.forename: Wendy
authors.initials: W
authors.lastname: Cozen
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordon-Cardo
authors.forename: Baoguo
authors.initials: B
authors.lastname: Ding
authors.forename: Sander
authors.initials: S
authors.lastname: Greenland
authors.forename: Na
authors.initials: N
authors.lastname: He
authors.forename: Shehnaz K
authors.initials: SK
authors.lastname: Hussain
authors.forename: Qingwu
authors.initials: Q
authors.lastname: Jiang
authors.forename: Yuan-Chin A
authors.initials: YC
authors.lastname: Lee
authors.forename: Simin
authors.initials: S
authors.lastname: Liu
authors.forename: Ming-Lan
authors.initials: ML
authors.lastname: Lu
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Mack
authors.forename: Jenny T
authors.initials: JT
authors.lastname: Mao
authors.forename: Hal
authors.initials: H
authors.lastname: Morgenstern
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Mu
authors.forename: Sam S
authors.initials: SS
authors.lastname: Oh
authors.forename: Allan
authors.initials: A
authors.lastname: Pantuck
authors.forename: Jeanette C
authors.initials: JC
authors.lastname: Papp
authors.forename: Jianyu
authors.initials: J
authors.lastname: Rao
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.forename: Donald P
authors.initials: DP
authors.lastname: Tashkin
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Nai-Chieh Y
authors.initials: NC
authors.lastname: You
authors.forename: Shun-Zhang
authors.initials: SZ
authors.lastname: Yu
authors.forename: Jin-Kou
authors.initials: JK
authors.lastname: Zhao
authors.forename: Zuo-Feng
authors.initials: ZF
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000009:adverse effects*
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins