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Tobacco smoking and death from prostate cancer in US veterans

Prostate Cancer and Prostatic Diseases volume 23, pages 252–259 (2020)Cite this article

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Abstract

Background

Cigarette smoking is a risk factor for mortality in several genitourinary cancers, likely due to accumulation of carcinogens in urine. However, in prostate cancer (PC) the link has been less studied. We evaluated differences in prostate cancer-specific mortality (PCSM) between current smokers, past smokers, and never smokers diagnosed with PC.

Methods

This was a retrospective cohort study of PCSM in men diagnosed with PC between 2000 and 2015 treated in the US Veterans Affairs health care system, using competing risk regression analyses.

Results

The cohort included 73,668 men (current smokers: 22,608 (30.7%), past smokers: 23,695 (32.1%), and never smokers: 27,365 (37.1%)). Median follow-up was 5.9 years. Current smoker patients were younger at presentation (median age current: 63, never: 66; p < 0.001), and had more advanced disease stage (stage IV disease current: 5.3%, never: 4.3%; p < 0.04). The 10-year incidence of PCSM was 5.2%, 4.8%, and 4.5% for current, past, and never smokers, respectively. On competing risk regression, current smoking was associated with increased PCSM (subdistribution hazard ratio: 1.14, 95% confidence interval: (1.05–1.24), p = 0.002), whereas past smoking was not. Hierarchical regression suggests that this increased risk was partially attributable to tumor characteristics.

Conclusions

Smoking at the time of diagnosis is associated with a higher risk of dying from PC as well as other causes of death. In contrast, past smoking was not associated with PCSM suggesting that smoking may be a modifiable risk factor. PC diagnosis may be an important opportunity to discuss smoking cessation.

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References

  1. Services, U. S. D. How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease: a report of the surgeon general. Rep No. 2010;9780160840784:792.

    Google Scholar 

  2. Cumberbatch MG, Rota M, Catto JWF, La Vecchia C. The role of tobacco smoke in bladder and kidney carcinogenesis: a comparison of exposures and meta-analysis of incidence and mortality risks. Eur Urol. 2016;70:458–66. https://doi.org/10.1016/j.eururo.2015.06.042

    Article  CAS  PubMed  Google Scholar 

  3. Zeegers MPA, Tan FES, Dorant E, Van Den Brandt PA. The impact of characteristics of cigarette smoking on urinary tract cancer risk: a meta-analysis of epidemiologic studies. Cancer. 2000;89:630–9. 10.1002/1097-0142(20000801)89:3<630:AID-CNCR19>3.0.CO;2-Q

    Article  CAS  Google Scholar 

  4. Steinberger E, Kollmeier M, McBride S, Novak C, Pei X, Zelefsky M. Cigarette smoking during external beam radiation therapy for prostate cancer is associated with an increased risk of prostate cancer-specific mortality and treatment-related toxicity. BJU Int. 2015;116:596–603. https://doi.org/10.1111/bju.12969

    Article  CAS  PubMed  Google Scholar 

  5. Kenfield SA, Stampfer MJ, Chan JM, Giovannucci E. Smoking and prostate cancer survival and recurrence. JAMA. 2011;305:2548. https://doi.org/10.1001/jama.2011.879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Islami F, Moreira DM, Boffetta P, Freedland SJ. A systematic review and meta-analysis of tobacco use and prostate cancer mortality and incidence in prospective cohort studies. Eur Urol. 2014;66:1054–64. https://doi.org/10.1016/j.eururo.2014.08.059

    Article  PubMed  PubMed Central  Google Scholar 

  7. Foerster B, Pozzo C, Abufaraj A, Mari A, Kimura S, D’Anrea D, et al. Association of smoking status with recurrence, metastasis, and mortality among patients with localized prostate cancer undergoing prostatectomy or radiotherapy. JAMA Oncol. 2018;4:953. https://doi.org/10.1001/jamaoncol.2018.1071

    Article  PubMed  PubMed Central  Google Scholar 

  8. Huncharek M, Haddock KS, Reid R, Kupelnick B. Smoking as a risk factor for prostate cancer: a meta-analysis of 24 prospective cohort studies. Am J Public Health. 2010;100:693–701. https://doi.org/10.2105/AJPH.2008.150508

    Article  PubMed  PubMed Central  Google Scholar 

  9. US Department of veterans affairs. VA informatics and computing infrastructure (VINCI). https://www.hsrd.research.va.gov/for_researchers/vinci/

  10. Pannek, J, Marks, L, Pearson, J, Rittenhouse, H, Chan, D, Shery, E, et al. Influence of finasteride on free and total serum prostate specific antigen levels in men with benign prostatic hyperplasia. J Urol. 1998;159:449–53.

  11. Calhoun, PS, Wilson, S, Hertzber, J, Kirby, A, McDonald, S, Dennis, P, et al. Validation of veterans affairs electronic medical record smoking data among Iraq- and Afghanistan-era veterans. J Gen Internal Med. 2017;32;1228–34.

  12. Guo DP, Thomas I, Mittakanti H, Selton J, Makarov D, Skolarus T, et al. The research implications of prostate specific antigen registry errors: data from the veterans health administration. J Urol. 2018;200:541–8.

    Article  Google Scholar 

  13. Thompson IM, Ankerst D, Chi C, Tangen C, Lucia M, et al. Assessing prostate cancer risk: results from the prostate cancer prevention trial. J Natl Cancer Inst. 2006;98:529–34. https://doi.org/10.1093/jnci/djj131

    Article  PubMed  Google Scholar 

  14. Klabunde CN, Potosky AL, Legler JM, Warren JL. Development of a comorbidity index using physician claims data. J Clin Epidemiol. 2000;53:1258–67.

    Article  CAS  Google Scholar 

  15. Wickham H. Tidyverse: easily install and load the ‘Tidyverse’. 2017. http://tidyverse.tidyverse.org, https://github.com/tidyverse/tidyverse.

  16. Gray B. Cmprsk: subdistribution analysis of competing risks. 2014. http://CRAN.R-project.org/package=cmprsk

  17. Therneau TM, Grambsch PM. A package for survival analysis in S. version 2.38, https://CRAN.R-project.org/package=survival 2015.

  18. Mathur MB, Ding P, Riddell CA, VanderWeele TJ. Website and R package for computing e-values. Epidemiology. 2018;29:e45–e47.

    Article  Google Scholar 

  19. Haneuse S, VanderWeele TJ, Arterburn D. Using the e-value to assess the potential effect of unmeasured confounding in observational studies. JAMA. 2019;321:602. https://doi.org/10.1001/jama.2018.21554

    Article  PubMed  Google Scholar 

  20. Fedak KM, Bernal A, Capshaw ZA, Gross S. Applying the Bradford Hill criteria in the 21st century: how data integration has changed causal inference in molecular epidemiology. Emerg Themes Epidemiol. 2015;12:14.

    Article  Google Scholar 

  21. Shui IM, Wong C, Zhao S, Kolb S, Ebot E, Geybels M, et al. Prostate tumor DNA methylation is associated with cigarette smoking and adverse prostate cancer outcomes. Cancer. 2016;122:2168–77. https://doi.org/10.1002/cncr.30045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Birrane G, Li H, Yang S, Tachado SD, Seng S. Cigarette smoke induces nuclear translocation of heme oxygenase 1 (HO-1) in prostate cancer cells: Nuclear HO-1 promotes vascular endothelial growth factor secretion. Int J Oncol. 2013;42:1919–28. https://doi.org/10.3892/ijo.2013.1910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Moreira DM, Gerber L,m, Muller R, Andriole G, Castro-Santamaria R, et al. Smoking is associated with acute and chronic prostatic inflammation: Results from the REDUCE study. Cancer Prev Res. 2015;8:312–7. https://doi.org/10.1158/1940-6207.CAPR-14-0260

    Article  CAS  Google Scholar 

  24. Wu X, Shu X. Epidemiology of renal cell carcinoma. Ren Cell Carcinoma. 2017;75:1–18. https://doi.org/10.1007/978-4-431-55531-5_1

    Article  Google Scholar 

  25. Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F. Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol. 2016;71:96–108. https://doi.org/10.1016/j.eururo.2016.06.010

    Article  PubMed  Google Scholar 

  26. Freedman ND, Silverman DT, Hollenbeck AR, Schatzkin A, Abnet CC. Association between smoking and risk of bladder cancer among men and women. JAMA. 2011;306:737. https://doi.org/10.1001/jama.2011.1142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Melzer AC, Pinsker E, Clothier B, Noorbaloochi S, Burgess DJ, Danan ER, et al. Validating the use of veterans affairs tobacco health factors for assessing change in smoking status: accuracy, availability, and approach. BMC Med Res Methodol. 2018;18:39. https://doi.org/10.1186/s12874-018-0501-2

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

The project described was partially supported by the National Institutes of Health, Grant TL1TR001443 (PR, AKB, AK, RRS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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Authors and Affiliations

  1. Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA

    Paul Riviere, Abhishek Kumar, Elaine Luterstein, Lucas K. Vitzthum, Vinit Nalawade, Reith R. Sarkar, Alex K. Bryant, John P. Einck, Arno J. Mundt, James D. Murphy & Brent S. Rose

  2. VA San Diego Health Care System, La Jolla, CA, USA

    Paul Riviere, Abhishek Kumar, Lucas K. Vitzthum, Vinit Nalawade, Reith R. Sarkar, Alex K. Bryant, James D. Murphy & Brent S. Rose

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  1. Paul Riviere
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Contributions

Conception: PR, AK, JM, and BR; Data analysis/acquisition: PR, AK, EL, LK, VN, RS, and AB; Draft writing: PR, AK, and BS; Editing and reviewing: All authors; Approval of final manuscript: all authors.

Corresponding author

Correspondence to Brent S. Rose.

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Conflict of interest

PR discloses previous salary support from Peptide Logic, LLC. AKB discloses consulting fees from Boston Consulting Group. Reith R. Sarkar discloses consulting fees from Boston Consulting Group. AK discloses consulting fees from and ownership stake in Sympto Health. JDM disclose consulting fees from Boston Consulting Group and ownership stake in Sympto Health. The remaining authors declare that they have no conflict of interest.

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Riviere, P., Kumar, A., Luterstein, E. et al. Tobacco smoking and death from prostate cancer in US veterans. Prostate Cancer Prostatic Dis 23, 252–259 (2020). https://doi.org/10.1038/s41391-019-0178-6

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