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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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Abstract

Purpose

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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Zhejiang Provincial CDC, Hangzhou, Zhejiang, People’s Republic of China

    Tingting Yang

  2. Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), 71-225 CHS, 650 Charles E Young Drive, South, Box 951772, Los Angeles, CA, 90095-1772, USA

    Tingting Yang, Po-Yin Chang, Delara Bastani, Shen-Chih Chang, Sander Greenland & Zuo-Feng Zhang

  3. Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA

    Sungshim Lani Park

  4. Departments of Epidemiology, Environmental Health Sciences, and Urology, Schools of Public Health and Medicine, and Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA

    Hal Morgenstern

  5. Division of Pulmonary and Critical Care Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, USA

    Donald P. Tashkin

  6. Pulmonary and Critical Care Section, New Mexico VA Healthcare System, Albuquerque, NM, USA

    Jenny T. Mao

  7. Department of Human Genetics, UCLA, Los Angeles, CA, USA

    Jeanette C. Papp

  8. Department of Pathology, UCLA David Geffen School of Medicine, Los Angeles, CA, USA

    Jian-Yu Rao

  9. Departments of Preventive Medicine and Pathology, Keck School of Medicine at University of Southern California, Los Angeles, CA, USA

    Wendy Cozen & Thomas M. Mack

  10. Department of Statistics, UCLA, Los Angeles, CA, USA

    Sander Greenland

  11. Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA

    Zuo-Feng Zhang

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  1. Tingting Yang
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Correspondence to Zuo-Feng Zhang.

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Tingting Yang and Po-Yin Chang made equal contributions to this paper.

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Yang, T., Chang, PY., Park, S.L. et al. Tobacco smoking, NBS1 polymorphisms, and survival in lung and upper aerodigestive tract cancers with semi-Bayes adjustment for hazard ratio variation. Cancer Causes Control 25, 11–23 (2014). https://doi.org/10.1007/s10552-013-0303-0

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