Dataset Information

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

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; HR1-<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.

SUBMITTER: Petrick JL

PROVIDER: S-EPMC5931109 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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

Petrick Jessica L JL Campbell Peter T PT Koshiol Jill J Thistle Jake E JE Andreotti Gabriella G Beane-Freeman Laura E LE Buring Julie E JE Chan Andrew T AT Chong Dawn Q DQ Doody Michele M MM Gapstur Susan M SM Gaziano John Michael JM Giovannucci Edward E Graubard Barry I BI Lee I-Min IM Liao Linda M LM Linet Martha S MS Palmer Julie R JR Poynter Jenny N JN Purdue Mark P MP Robien Kim K Rosenberg Lynn L Schairer Catherine C Sesso Howard D HD Sinha Rashmi R Stampfer Meir J MJ Stefanick Marcia M Wactawski-Wende Jean J Zhang Xuehong X Zeleniuch-Jacquotte Anne A Freedman Neal D ND McGlynn Katherine A KA

British journal of cancer 20180309 7

<h4>Background</h4>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.<h4>Methods</h4>The Liver Cancer Pooling Project is a consortium of 14 US-based prospective cohort studies that includes data from 1,518,741 individuals (HCC ...[more]

PMID: 29520041

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Project description:Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the two most common pathology subtypes of primary liver cancer (PLC). Identifying DNA methylation biomarkers for diagnosis of PLC and further distinguishing HCC from ICC plays a vital role in subsequent treatment options selection. To obtain potential diagnostic DNA methylation sites for PLC, differentially methylated CpG (DMC) sites were first screened by comparing the methylation data between normal liver samples and PLC samples (ICC samples and HCC samples). A random forest algorithm was then used to select specific DMC sites with top Gini value. To avoid overfitting, another cohort was taken as an external validation for evaluating the area under curves (AUCs) of different DMC sites combination. A similar model construction strategy was applied to distinguish HCC from ICC. In addition, we identified DNA Methylation-Driven Genes in HCC and ICC via MethylMix method and performed pathway analysis by utilizing MetaCore. Finally, we not only performed methylator phenotype based on independent prognostic sites but also analyzed the correlations between methylator phenotype and clinical factors in HCC and ICC, respectively. To diagnose PLC, we developed a model based on three PLC-specific methylation sites (cg24035245, cg21072795, and cg00261162), whose sensitivity and specificity achieved 98.8%,94.8% in training set and 97.3%,81% in validation set. Then, to further divide the PLC samples into HCC and ICC, we established another mode through three methylation sites (cg17769836, cg17591574, and cg07823562), HCC accuracy and ICC accuracy achieved 95.8%, 89.8% in the training set and 96.8%,85.4% in the validation set. In HCC, the enrichment pathways were mainly related to protein folding, oxidative stress, and glutathione metabolism. While in ICC, immune response, embryonic hepatocyte maturation were the top pathways. Both in HCC and ICC, methylator phenotype correlated well with overall survival time and clinical factors involved in tumor progression. In summary, our study provides the biomarkers based on methylation sites not only for the diagnosis of PLC but also for distinguishing HCC from ICC.

Dataset Information

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

Publications

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

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