Tobacco Smoking, Alcohol Use And Risk Of Hepatocellular Carcinoma And Intrahepatic Cholangiocarcinoma: The Liver Cancer Pooling Project

Background: Since 1980, liver cancer has been among the most rapidly increasing cancer types in the United States (US), with 5-year survival rates of approximately 17%. While tobacco and alcohol are known to be associated with primary liver cancer, it is unclear whether they only increase the risk of hepatocellular carcinoma (HCC), the most common type of liver cancer, or whether they also increase risk of intrahepatic cholangiocarcinoma (ICC), second most common histologic type. Additionally, it is unclear what amount of alcohol consumption is associated with an increased risk of liver cancer. As liver cancer is a rare cancer type, we conducted a study of pooled data from the National Cancer Institute Cohort Consortium to examine the associations between smoking and alcohol use and liver cancer, stratified by histologic subtype. Methods: In the Liver Cancer Pooling Project, a consortium of US-based cohort studies, we pooled data from 1,518,741 individuals (HCC n=1,423, ICC n=410) in 14 cohorts. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Cubic splines were used to model the association between alcohol and liver cancer risk. Results: Compared to never smokers, both former and current smokers at study baseline had an increased risk of ICC (HR=1.32, 95% CI: 1.03-1.68 and HR=1.47, 95% CI: 1.07-2.02, respectively) and HCC (HR=1.24, 95% CI: 1.08-1.43 and HR=1.86, 95% CI: 1.57-2.20, respectively). This finding was consistent for heavier smoking intensity, longer duration of smoking, and more pack-years of smoking. Heavy alcohol consumption was associated with an 87% increased risk of HCC (HR ≥7 drinks/day v. non-drinker =1.87, 95% CI: 1.41-2.47) and a non-significant 68% increased risk of ICC (HR ≥5 drinks/day v. non-drinker =1.68, 95% CI: 0.99-2.86). Risk of HCC significantly increased at 4.5 alcoholic drinks per day, while risk of ICC was non-significantly increased with any amount of consumption. Conclusions: These findings suggest that, in a US population, cigarette smoking is associated with an increased risk of both histologic subtypes of primary liver cancer - HCC and ICC. In contrast, alcohol consumption was primarily associated with an increased risk of HCC. These results suggest that smoking cessation and alcohol reduction programs could be important intervention opportunities for these lethal cancer types. Citation Format: Jessica Leigh Petrick, Peter T. Campbell, Jill Koshiol, Jake E. Thistle, Gabriella Andreotti, Laura E. Beane-Freeman, Julie E. Buring, Andrew T. Chan, Dawn Q. Chong, Michele M. Doody, Susan M. Gapstur, John Michael Gaziano, Edward Giovannucci, Barry I. Graubard, I-Min Lee, Linda M. Liao, Martha S. Linet, Julie R. Palmer, Jenny N. Poynter, Mark P. Purdue, Kim Robien, Lynn Rosenberg, Catherine Schairer, Howard D. Sesso, Rashmi Sinha, Meir J. Stampfer, Marcia Stefanick, Jean Wactawski-Wende, Xuehong Zhang, Anne Zeleniuch-Jacquotte, Neal D. Freedman, Katherine A. McGlynn. Tobacco smoking, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3007. doi:10.1158/1538-7445.AM2017-3007