Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project

doi:10.1038/s41416-018-0007-z

. 2018 Apr;118(7):1005-1012.

doi: 10.1038/s41416-018-0007-z. Epub 2018 Mar 9.

Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project

Jessica L Petrick¹, Peter T Campbell², Jill Koshiol³, Jake E Thistle³, Gabriella Andreotti³, Laura E Beane-Freeman³, Julie E Buring^{4

5}, Andrew T Chan^{5

6

7}, Dawn Q Chong⁸, Michele M Doody³, Susan M Gapstur², John Michael Gaziano^{4

9}, Edward Giovannucci¹⁰, Barry I Graubard³, I-Min Lee^{4

10}, Linda M Liao³, Martha S Linet³, Julie R Palmer¹¹, Jenny N Poynter¹², Mark P Purdue³, Kim Robien¹³, Lynn Rosenberg¹¹, Catherine Schairer³, Howard D Sesso^{4

10}, Rashmi Sinha³, Meir J Stampfer^{5

10

14}, Marcia Stefanick¹⁵, Jean Wactawski-Wende¹⁶, Xuehong Zhang⁵, Anne Zeleniuch-Jacquotte¹⁷, Neal D Freedman³, Katherine A McGlynn³

Affiliations

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. jessica.petrick@nih.gov.
² Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
⁴ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁵ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁶ Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
⁹ VA Boston Healthcare System, Boston, MA, USA.
¹⁰ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹¹ Slone Epidemiology Center at Boston University, Boston, MA, USA.
¹² Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
¹³ Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington, DC, USA.
¹⁴ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹⁵ Department of Medicine and Obstetrics & Gynecology, Stanford University School of Medicine, Stanford, CA, USA.
¹⁶ Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA.
¹⁷ Department of Population Health, New York University School of Medicine, New York, NY, USA.

PMID: 29520041
PMCID: PMC5931109
DOI: 10.1038/s41416-018-0007-z

Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project

Jessica L Petrick et al. Br J Cancer. 2018 Apr.

. 2018 Apr;118(7):1005-1012.

doi: 10.1038/s41416-018-0007-z. Epub 2018 Mar 9.

Authors

Affiliations

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. jessica.petrick@nih.gov.
² Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
⁴ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁵ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁶ Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
⁹ VA Boston Healthcare System, Boston, MA, USA.
¹⁰ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹¹ Slone Epidemiology Center at Boston University, Boston, MA, USA.
¹² Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
¹³ Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington, DC, USA.
¹⁴ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹⁵ Department of Medicine and Obstetrics & Gynecology, Stanford University School of Medicine, Stanford, CA, USA.
¹⁶ Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA.
¹⁷ Department of Population Health, New York University School of Medicine, New York, NY, USA.

PMID: 29520041
PMCID: PMC5931109
DOI: 10.1038/s41416-018-0007-z

Abstract

Background: While tobacco and alcohol are established risk factors for hepatocellular carcinoma (HCC), the most common type of primary liver cancer, it is unknown whether they also increase the risk of intrahepatic cholangiocarcinoma (ICC). Thus, we examined the association between tobacco and alcohol use by primary liver cancer type.

Methods: The Liver Cancer Pooling Project is a consortium of 14 US-based prospective cohort studies that includes data from 1,518,741 individuals (HCC n = 1423, ICC n = 410). Multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression.

Results: Current smokers at baseline had an increased risk of HCC (hazard ratio (HR) = 1.86, 95% confidence interval (CI): 1.57-2.20) and ICC (HR = 1.47, 95% CI: 1.07-2.02). Among individuals who quit smoking >30 years ago, HCC risk was almost equivalent to never smokers (HR = 1.09, 95% CI: 0.74-1.61). Compared to non-drinkers, heavy alcohol consumption was associated with an 87% increased HCC risk (HR_{≥7 drinks/day} = 1.87, 95% CI: 1.41-2.47) and a 68% increased ICC risk (HR_{≥5 drinks/day} = 1.68, 95% CI: 0.99-2.86). However, light-to-moderate alcohol consumption of <3 drinks/day appeared to be inversely associated with HCC risk (HR_{>0-<0.5 drinks/day} = 0.77, 95% CI: 0.67-0.89; HR_{>0.5-<1 drinks/day} = 0.57, 95% CI: 0.44-0.73; HR_{1-<3 drinks/day} = 0.71, 95% CI: 0.58-0.87), but not ICC.

Conclusions: These findings suggest that, in this relatively healthy population, smoking cessation and light-to-moderate drinking may reduce the risk of HCC.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

**Fig. 1**
Cubic spline graph of the multivariate-adjusted HRs (represented by the solid line) and 95% CIs (represented by the dotted lines) for the association between smoking intensity and a HCC and b ICC in the Liver Cancer Pooling Project (knots: 0.5, 10, 15, 25; referent: 0)

**Fig. 2**
Cubic spline graph of the multivariate-adjusted HRs (represented by the solid line) and 95% CIs (represented by the dotted lines) for the association between drinks per day of alcohol and a HCC (knots: 1, 3, 5, and 7; referent: 0.25) and b ICC (knots: 1, 3, and 5; referent: 0.25) in the Liver Cancer Pooling Project

See this image and copyright information in PMC

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References

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[1] IARC. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Tobacco Smoke and Involuntary Smoking. Lyon, France: IARC; 2004. - PMC - PubMed

[2] IARC. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Tobacco Smoke and Involuntary Smoking. Lyon, France: IARC; 2004. - PMC - PubMed

[3] Office of the Surgeon General. The Health Consequences of Smoking--50 Years of Progress: A Report Of The Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, Office of the Surgeon General; 2014.

[4] Office of the Surgeon General. The Health Consequences of Smoking--50 Years of Progress: A Report Of The Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, Office of the Surgeon General; 2014.

[5] Bosetti C, Turati F, La Vecchia C. Hepatocellular carcinoma epidemiology. Best Pract. Res Clin. Gastroenterol. 2014;28:753–770. doi: 10.1016/j.bpg.2014.08.007. - DOI - PubMed

[6] Bosetti C, Turati F, La Vecchia C. Hepatocellular carcinoma epidemiology. Best Pract. Res Clin. Gastroenterol. 2014;28:753–770. doi: 10.1016/j.bpg.2014.08.007. - DOI - PubMed

[7] McGlynn KA, London WT. The global epidemiology of hepatocellular carcinoma: present and future. Clin. Liver Dis. 2011;15:223–243. doi: 10.1016/j.cld.2011.03.006. - DOI - PMC - PubMed

[8] McGlynn KA, London WT. The global epidemiology of hepatocellular carcinoma: present and future. Clin. Liver Dis. 2011;15:223–243. doi: 10.1016/j.cld.2011.03.006. - DOI - PMC - PubMed

[9] Lee YC, et al. Meta-analysis of epidemiologic studies on cigarette smoking and liver cancer. Int. J. Epidemiol. 2009;38:1497–1511. doi: 10.1093/ije/dyp280. - DOI - PubMed

[10] Lee YC, et al. Meta-analysis of epidemiologic studies on cigarette smoking and liver cancer. Int. J. Epidemiol. 2009;38:1497–1511. doi: 10.1093/ije/dyp280. - DOI - PubMed

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Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project

Affiliations

Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project

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