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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.

SUBMITTER: Park SL

PROVIDER: S-EPMC2893801 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Associations between NBS1 polymorphisms, haplotypes and smoking-related cancers.

Park Sungshim L SL Bastani Delara D Goldstein Binh Y BY Chang Shen-Chih SC Cozen Wendy W Cai Lin L Cordon-Cardo Carlos C Ding Baoguo B Greenland Sander S He Na N Hussain Shehnaz K SK Jiang Qingwu Q Lee Yuan-Chin A YC Liu Simin S Lu Ming-Lan ML Mack Thomas M TM Mao Jenny T JT Morgenstern Hal H Mu Li-Na LN Oh Sam S SS Pantuck Allan A Papp Jeanette C JC Rao Jianyu J Reuter Victor E VE Tashkin Donald P DP Wang Hua H You Nai-Chieh Y NC Yu Shun-Zhang SZ Zhao Jin-Kou JK Zhang Zuo-Feng ZF

Carcinogenesis 20100517 7

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 Cance ...[more]

PMID: 20478923

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Project description:Importance:The population of cancer survivors is rapidly growing in the US. Tobacco smoking is associated with many cancers; however, whether cigarette smoking behaviors among cancer survivors vary according to cancer type-that is, smoking-related cancers (SRCs) vs non-smoking-related cancers (NSRCs)-remains unclear. Objectives:To examine cigarette smoking prevalence and behaviors (ie, continuing or quitting smoking) among cancer survivors and to compare them between survivors of SRCs and NSRCs. Design, Setting, and Participants:This study was a cross-sectional analysis of the 2017 National Health Interview Survey, a household survey of civilian US residents who were aged 18 years or older. The National Health Interview Survey is population based and is representative of the US population. Data analysis was performed from June to October 2019. Main Outcomes and Measures:The primary outcomes were prevalence of current cigarette smoking among cancer survivors and prevalence of continuing smoking and quitting smoking after a cancer diagnosis. Secondary outcomes included factors associated with continued smoking vs quitting smoking after a cancer diagnosis. Results:A total of 26?742 respondents (mean [SD] age, 50.97 [18.61] years; 14?646 women [51.76%]) to the 2017 National Health Interview Survey were included in this study. Of the 3068 individuals (9.42%) in the study population who had cancer, 589 (19.96%) were SRC survivors, 2297 (74.50%) were NSRC survivors, 168 (4.96%) were survivors of both SRC and NSRC, and the remaining 14 (0.58%) had missing information about the type of cancer. Four hundred forty-nine SRC survivors (54.08%) were women, compared with 1412 NSRC survivors (54.30%). Ninety-six SRC survivors (15.69%) and 151 NSRC survivors (7.99%) were younger than 45 years. Overall, 372 cancer survivors (13.16%) were current smokers. Current smoking prevalence was higher among survivors of SRCs (145 survivors [19.78%]) compared with NSRC survivors (251 survivors [10.63%]). Among cancer survivors, 309 current smokers at cancer diagnosis (43.96%) reported having successfully quit smoking and 372 (56.04%) reported continuing smoking. Among the continuing smokers, 176 (56.49%) reported an unsuccessful quit attempt in the last 12 months. After cancer diagnosis, SRC survivors had higher odds of continued smoking compared with NSRC survivors (odds ratio [OR], 2.10; 95% CI, 1.12-3.93; P?=?.02). Men (OR, 1.93; 95% CI, 1.05-3.57; P?=?.04), those with angina pectoris (OR, 5.40; 95% CI, 1.33-21.91; P?=?.02), and those with chronic bronchitis (OR, 2.55; 95% CI, 1.05-6.19; P?=?.04) had higher odds of continued smoking, whereas Hispanic participants (compared with non-Hispanic white participants: OR, 0.18; 95% CI, 0.05-0.68; P?=?.01) and married participants (compared with never married participants: OR, 0.33; 95% CI, 0.12-0.96; P?=?.04) had lower odds of continued smoking. Conclusions and Relevance:These findings suggest that compared with NSRC survivors, SRC survivors may be at higher risk of being cigarette smokers at cancer diagnosis and of continuing smoking afterward. Although smoking cessation interventions are critically important for all cancer survivors, special efforts should target survivors of SRCs.

Project description:IntroductionThe human multidrug resistance gene ATP-binding cassette B1 (ABCB1) codes for P-glycoprotein (P-gp), an important membrane-bound efflux transporter known to confer anticancer drug resistance as well as affect the pharmacokinetics of many drugs and xenobiotics. A number of single nucleotide polymorphisms (SNPs) have been identified throughout the ABCB1 gene that may have an effect on P-gp expression levels and function. Haplotype as well as genotype analysis of SNPs is becoming increasingly important in identifying genetic variants underlying susceptibility to human disease. Three SNPs, 1236C-->T, 2677G-->T and 3435C-->T, have been repeatedly shown to predict changes in the function of P-gp. The frequencies with which these polymorphisms exist in a population have also been shown to be ethnically related.MethodsIn this study, 95 individuals representative of the entire ethnic make-up of the USA were compared with 101 individuals from an Ashkenazi-Jewish population. These individuals were analyzed by genomic sequencing and polymerase chain reaction, using restriction fragment length polymorphisms, to calculate their genotype frequencies.ResultsA total of 25 SNPs were located in the exons of the ABCB1 gene. All of the polymorphisms identified were in parts of the ABCB1 gene product predicted to be intracellular, and 16 appear to be novel as compared with those listed by the National Center for Biotechnological Information. Frequencies of the 1236C-->T and 2677G-->T/A/C SNPs were similar for the US and Ashkenazi populations (64.2 and 60.4%, respectively for 1236C-->T [chi2: 0.30; p < or = 1]; 55.8 and 64.4%, respectively for 2677G-->T/A/C [chi2: 1.49; p < or = 1]), but were different for 3435C-->T (24.2% for the US population and 69.3% for the Ashkenazi population [chi2: 39.927; p < or = 0.001]). The 1236T/ 2677T/3435T haplotype occurred in 23.6% (standard error: 0.013) of the Ashkenazi population.ConclusionThe SNP at location 3435C-->T plays a significant role in the ABCB1 gene. The haplotype and genotype analysis from these data may be used as a basis for studies on the relationship between ABCB1 genotypes and drug efficacy, drug toxicity, disease susceptibility or other phenotypes.

Dataset Information

Associations between NBS1 polymorphisms, haplotypes and smoking-related cancers.

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Associations between NBS1 polymorphisms, haplotypes and smoking-related cancers.

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