Tobacco smoking, NBS1 polymorphisms, and survival in lung and upper aerodigestive tract cancers with semi-Bayes adjustment for hazard ratio variation
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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.
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.
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).
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.
KeywordsSurvival NBS1 Lung cancer Upper aerodigestive tract (UADT) cancers Tobacco Bayesian methods
The authors thank all of the Los Angeles Study participants for their time and effort in supporting this study. This research was supported by the National Institutes of Health [Grant Numbers ES06718, ES01167, CA90833, CA077954, CA09142, CA96134, DA11386] and the Alper Research Center for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center.
Conflict of interest
The authors declare that they have no potential conflicts of interest.
- 3.Hoyert DL, Xu J (2012) National vital statistics reports. Deaths: preliminary data for 2011. Division of Vital Statistics. CDC/National Center for Health Statistics. vol 61, p 6Google Scholar
- 21.Greene FL, Page DL, Fleming ID et al (eds) (2002) AJCC cancer staging manual, 6th edn. Springer, New YorkGoogle Scholar
- 22.Vaughan TL, Davis S, Kristal A, Thomas DB (1995) Obesity, alcohol, and tobacco as risk factors for cancers of the esophagus and gastric cardia: adenocarcinoma versus squamous cell carcinoma. Cancer Epidemiol Biomark Prev 4:85–92Google Scholar
- 33.Greenland S (2008) Introduction to regression models. In: Rothman KJ, Greenland S, Lash TL (eds) Modern epidemiology, 3rd edn. Lippincott-Williams-Wilkins, Philadelphia, p 405Google Scholar