Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: the Liver Cancer Pooling Project
Open accessAbstract
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. 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. 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. 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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Smoking is associated with an increased risk of HCC independent of aetiology as well as in MASLD specifically.
“Smoking has been associated with an increased risk of HCC independent of aetiology 72 as well as in MASLD speci fi cally.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [72]
The Discussion reports an increased HCC risk associated with smoking, and the Results report no evidence that the smoking–HCC association was modified by the factors examined. The paper does not establish that the association holds independently of every HCC aetiology; HBV/HCV status was unavailable for some participants. The citation appears before the separate MASLD-specific clause, so that clause is not assessed here. (LLM, conf=0.83)
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- Authors
- Petrick, J. L., Campbell, P. T., Koshiol, J., Thistle, J. E., Andreotti, G., Beane-Freeman, L. E., Buring, J. E., Chan, A. T., Chong, D. Q., Doody, M. M., Gapstur, S. M., Gaziano, J. M., Giovannucci, E., Graubard, B. I., Lee, I.-M., Liao, L. M., Linet, M. S., Palmer, J. R., Poynter, J. N., Purdue, M. P., Robien, K., Rosenberg, L., Schairer, C., Sesso, H. D., Sinha, R., Stampfer, M. J., Stefanick, M., Wactawski-Wende, J., Zhang, X., Zeleniuch-Jacquotte, A., Freedman, N. D., & McGlynn, K. A.
- Affiliations
- National Cancer Institute (US)
- American Cancer Society (US)
- Brigham and Women's Hospital (US)
- National Cancer Centre Singapore (SG)
- Harvard University (US)
- Boston University (US)
- University of Minnesota (US)
- George Washington University (US)
- Stanford Medicine (US)
- Corresponding author
- Petrick, Jessica L.
- ORCID
- Petrick, Jessica L.
- Campbell, Peter T.
- Koshiol, Jill
- Thistle, Jake E.
- Andreotti, Gabriella
- Buring, Julie E.
- Chan, Andrew T.
- Chong, Dawn Q.
- Gapstur, Susan M.
- Gaziano, John Michael
- Giovannucci, Edward
- Graubard, Barry I.
- Lee, I-Min
- Liao, Linda M.
- Linet, Martha S.
- Palmer, Julie R.
- Poynter, Jenny N.
- Purdue, Mark P.
- Robien, Kim
- Rosenberg, Lynn
- Schairer, Catherine
- Sesso, Howard D.
- Sinha, Rashmi
- Stampfer, Meir J.
- Stefanick, Marcia
- Zhang, Xuehong
- Freedman, Neal D.
- McGlynn, Katherine A.
- Venue
- British Journal of Cancer
- Published
- 2018-03-09
- Volume
- 118
- Issue
- 7
- Pages
- 1005-1012
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC5931109
- OpenAlex
- W2789475596
- Cited by
- 257
- References
- 59
- Citations by year
- 2026: 22 · 2025: 37 · 2024: 46 · 2023: 27 · 2022: 46 · 2021: 28 · 2020: 24 · 2019: 21 · 2018: 5
- FWCI
- 12.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- British Journal of Cancer (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl043851-10, CA058420, CA164974, HL-043851, CA-167552, CA 87969, UM1-CA164974)
- National Heart, Lung, and Blood Institute (R01HL080467, R01‐HL043851, RC1HL099355)
- National Cancer Institute (CA 058420, K07CA188126, HL-080467, HL-099355, CA-167552, CA-87969, R01CA058420, HL-043851, UM1CA182934, P01CA087969, DK098311, CA-186107, CA164974, CA 047988, UM1CA164974, UM1CA186107, R01CA047988, UM1CA167552, U01CA164974, U01CA167552)
- National Institute of Diabetes and Digestive and Kidney Diseases (K24DK098311)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- hepatocellular carcinoma, intrahepatic cholangiocarcinoma, tobacco use, smoking, alcohol consumption, heavy drinking, light to moderate drinking, smoking cessation, liver cancer risk factors, primary liver cancer
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alcohol Drinking, Bile Duct Neoplasms, Bile Ducts, Intrahepatic, Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Middle Aged, Risk Factors, Smoking, Nicotiana, Cohort Studies, Case-Control Studies, Cholangiocarcinoma
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