title: Role of a genetic variant on the 15q25.1 lung cancer susceptibility locus in smoking-associated nasopharyngeal carcinoma.
abstract: BACKGROUND
  The 15q25.1 lung cancer susceptibility locus, containing CHRNA5, could modify lung cancer susceptibility and multiple smoking related phenotypes. However, no studies have investigated the association between CHRNA5 rs3841324, which has been proven to have the highest association with CHRNA5 mRNA expression, and the risk of other smoking-associated cancers, except lung cancer. In the current study we examined the association between rs3841324 and susceptibility to smoking-associated nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  In this case-control study we genotyped the CHRNA5 rs3841324 polymorphism with 400 NPC cases and 491 healthy controls who were Han Chinese and frequency-matched by age (±5 years), gender, and alcohol consumption. Univariate and multivariate logistic regression analyses were used to calculate the odds ratio (OR) and 95% confidence intervals (95% CI).
  
  
  RESULTS
  We found that individuals with CHRNA5 rs3841324 combined variant genotypes (ins/del+del/del) had a >1.5-fold elevated risk for NPC than those with the ins/ins genotype (adjusted OR = 1.52; 95% CI, 1.16-2.00), especially among ever smokers (adjusted OR = 2.07; 95% CI, 1.23-3.48). The combined variant genotypes acted jointly with cigarette smoking to contribute to a 4.35-fold increased NPC risk (adjusted OR = 4.35; 95% CI, 2.57-7.38). There was a dose-response relationship between deletion alleles and NPC susceptibility (trend test, P = 0.011).
  
  
  CONCLUSIONS
  Our results suggest that genetic variants on the 15q25.1 lung cancer susceptibility locus may influence susceptibility to NPC, particularly for smoking-associated NPC. Such work may be helpful to facilitate an understanding of the etiology of smoking-associated cancers and improve prevention efforts.
authors.affiliation: Department of Radiation Oncology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China; Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, United States of America.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, United States of America.
authors.forename: Jiang
authors.initials: J
authors.lastname: Gui
authors.affiliation: Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Anesthesia, Binzhou Medical University, Binzhou, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, United States of America.
authors.forename: Yafang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Oncology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: An
authors.affiliation: Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, United States of America.
authors.forename: Dakai
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Radiation Oncology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hu
mesh_terms: D000328:Adult; D002277:Carcinoma; D016022:Case-Control Studies; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000209:etiology / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*
chemical_list: C447158:CHRNA5 protein, human; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic