Associations between NBS1 polymorphisms, haplotypes and smoking-related cancers Journal Article
| Authors: | Park, S. L.; Bastani, D.; Goldstein, B. Y.; Chang, S. C.; Cozen, W.; Cai, L.; Cordon-Cardo, C.; Ding, B.; Greenland, S.; He, N.; Hussain, S. K.; Jiang, Q.; Lee, Y. C. A.; Liu, S.; Lu, M. L.; Mack, T. M.; Mao, J. T.; Morgenstern, H.; Mu, L. N.; Oh, S. S.; Pantuck, A.; Papp, J. C.; Rao, J.; Reuter, V. E.; Tashkin, D. P.; Wang, H.; You, N. C. Y.; Yu, S. Z.; Zhao, J. K.; Zhang, Z. F. |
| Article 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 (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. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org. |
| Keywords: | adolescent; adult; controlled study; aged; middle aged; major clinical study; case-control studies; polymorphism, single nucleotide; cancer incidence; neoplasm; neoplasms; cell cycle proteins; bayes theorem; lung neoplasms; haplotypes; linkage disequilibrium; lung cancer; smoking; bladder cancer; carcinogenesis; nibrin; haplotype; nuclear proteins; stomach cancer; liver cancer; esophagus cancer; dna polymorphism |
| Journal Title: | Carcinogenesis |
| Volume: | 31 |
| Issue: | 7 |
| ISSN: | 0143-3334 |
| Publisher: | Oxford University Press |
| Date Published: | 2010-07-01 |
| Start Page: | 1264 |
| End Page: | 1271 |
| Language: | English |
| DOI: | 10.1093/carcin/bgq096 |
| PUBMED: | 20478923 |
| PROVIDER: | scopus |
| PMCID: | PMC2893801 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: CRNGD" - "Source: Scopus" |
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