title: Tobacco smoking, NBS1 polymorphisms, and survival in lung and upper aerodigestive tract cancers with semi-Bayes adjustment for hazard ratio variation.
abstract: OBJECTIVE
  Although single nucleotide polymorphisms (SNPs) of NBS1 have been associated with susceptibility to lung and upper aerodigestive tract (UADT) cancers, their relations to cancer survival and measures of effect are largely unknown.
  
  
  METHODS
  Using follow-up data from 611 lung cancer cases and 601 UADT cancer cases from a population-based case-control study in Los Angeles, we prospectively evaluated associations of tobacco smoking and 5 NBS1 SNPs with all-cause mortality. Mortality data were obtained from the Social Security Death Index. We used Cox regression to estimate adjusted hazard ratios (HR) for main effects and ratios of hazard ratios (RHR) derived from product terms to assess hazard ratio variations by each SNP. Bayesian methods were used to account for multiple comparisons.
  
  
  RESULTS
  We observed 406 (66 %) deaths in lung cancer cases and 247 (41 %) deaths in UADT cancer cases with median survival of 1.43 and 1.72 years, respectively. Ever tobacco smoking was positively associated with mortality for both cancers. We observed an upward dose-response association between smoking pack-years and mortality in UADT squamous cell carcinoma. The adjusted HR relating smoking to mortality in non-small cell lung cancer (NSCLC) was greater for cases with the GG genotype of NBS1 rs1061302 than for cases with AA/AG genotypes (semi-Bayes adjusted RHR = 1.97; 95 % limits = 1.14, 3.41).
  
  
  CONCLUSIONS
  A history of tobacco smoking at cancer diagnosis was associated with mortality among patients with lung cancer or UADT squamous cell carcinoma. The HR relating smoking to mortality appeared to vary with the NBS1 rs1061302 genotype among NSCLC cases.
authors.affiliation: Zhejiang Provincial CDC, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Yang
authors.forename: Po-Yin
authors.initials: PY
authors.lastname: Chang
authors.forename: Sungshim Lani
authors.initials: SL
authors.lastname: Park
authors.forename: Delara
authors.initials: D
authors.lastname: Bastani
authors.forename: Shen-Chih
authors.initials: SC
authors.lastname: Chang
authors.forename: Hal
authors.initials: H
authors.lastname: Morgenstern
authors.forename: Donald P
authors.initials: DP
authors.lastname: Tashkin
authors.forename: Jenny T
authors.initials: JT
authors.lastname: Mao
authors.forename: Jeanette C
authors.initials: JC
authors.lastname: Papp
authors.forename: Jian-Yu
authors.initials: JY
authors.lastname: Rao
authors.forename: Wendy
authors.initials: W
authors.lastname: Cozen
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Mack
authors.forename: Sander
authors.initials: S
authors.lastname: Greenland
authors.forename: Zuo-Feng
authors.initials: ZF
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001499:Bayes Theorem; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D015141:Los Angeles; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects / Q000235:genetics*; D055815:Young Adult
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins