Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2018 Oct;113(10):1494-1505.
doi: 10.1038/s41395-018-0207-4. Epub 2018 Sep 3.

Body Mass Index, Diabetes and Intrahepatic Cholangiocarcinoma Risk: The Liver Cancer Pooling Project and Meta-analysis

Jessica L Petrick  1 , Jake E Thistle  1 , Anne Zeleniuch-Jacquotte  1 , Xuehong Zhang  1 , Jean Wactawski-Wende  1 , Alison L Van Dyke  1 , Meir J Stampfer  1   1   1 , Rashmi Sinha  1 , Howard D Sesso  1   1 , Catherine Schairer  1 , Lynn Rosenberg  1 , Thomas E Rohan  1 , Kim Robien  1 , Mark P Purdue  1 , Jenny N Poynter  1 , Julie R Palmer  1 , Christina C Newton  1 , Martha S Linet  1 , Linda M Liao  1 , I-Min Lee  1   1 , Jill Koshiol  1 , Cari M Kitahara  1 , Jonathan N Hofmann  1 , Barry I Graubard  1 , Edward Giovannucci  1   1   1 , Michael J Gaziano  1   1 , Susan M Gapstur  1 , Neal D Freedman  1 , Dawn Q Chong  1 , Andrew T Chan  1   1   1 , Julie E Buring  1   1 , Laura Beane E Freeman  1 , Peter T Campbell  1 , Katherine A McGlynn  1
Affiliations
Meta-Analysis

Body Mass Index, Diabetes and Intrahepatic Cholangiocarcinoma Risk: The Liver Cancer Pooling Project and Meta-analysis

Jessica L Petrick et al. Am J Gastroenterol. 2018 Oct.

Abstract

Objective: Obesity and diabetes are associated with an increased liver cancer risk. However, most studies have examined all primary liver cancers or hepatocellular carcinoma, with few studies evaluating intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. Thus, we examined the association between obesity and diabetes and ICC risk in a pooled analysis and conducted a systematic review/meta-analysis of the literature.

Design: For the pooled analysis, we utilized the Liver Cancer Pooling Project, a consortium of 13 US-based, prospective cohort studies with data from 1,541,143 individuals (ICC cases n = 414). In our systematic review, we identified 14 additional studies. We then conducted a meta-analysis, combining the results from LCPP with results from the 5 prospective studies identified through September 2017.

Results: In the LCPP, obesity and diabetes were associated with a 62% [Hazard Ratio (HR) = 1.62, 95% Confidence Interval (CI): 1.24-2.12] and an 81% (HR = 1.81, 95% CI: 1.33-2.46) increased ICC risk, respectively. In the meta-analysis of prospectively ascertained cohorts and nested case-control studies, obesity was associated with a 49% increased ICC risk [Relative Risk (RR) = 1.49, 95% CI: 1.32-1.70; n = 4 studies; I2 = 0%]. Diabetes was associated with a 53% increased ICC risk (RR = 1.53, 95% CI: 1.31-1.78; n = 6 studies). While we noted heterogeneity between studies (I2 = 67%) for diabetes, results were consistent in subgroup analyses. Results from hospital-based case-control studies (n = 9) were mostly consistent, but these studies are potentially subject to reverse causation.

Conclusions: These findings suggest that obesity and diabetes are associated with increased ICC risk, highlighting similar etiologies of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. However, additional prospective studies are needed to verify these associations.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Flow chart for systematic review of the association between obesity/diabetes and intrahepatic cholangiocarcinoma.
Figure 2
Figure 2
Meta-analysis of the association between obesity and intrahepatic cholangiocarcinoma risk by random-effects model in cohort and nested case-control studies (N=4 studies).
Figure 3
Figure 3
Meta-analysis of the association between diabetes and intrahepatic cholangiocarcinoma risk by random-effects model in cohort and nested case-control studies (N=6 studies).
See this image and copyright information in PMC

References

    1. Huang W, Ren H, Ben Q, et al. Risk of esophageal cancer in diabetes mellitus: a meta-analysis of observational studies. Cancer Causes Control 2012;23:263–72. - PubMed
    1. Wang Y, Wang B, Yan S, et al. Type 2 diabetes and gender differences in liver cancer by considering different confounding factors: a meta-analysis of cohort studies. Ann Epidemiol 2016;26:764–772. - PubMed
    1. Altekruse SF, Devesa SS, Dickie LA, et al. Histological classification of liver and intrahepatic bile duct cancers in SEER registries. J Registry Manag 2011;38:201–5. - PMC - PubMed
    1. Chapman RW. Risk factors for biliary tract carcinogenesis. Ann Oncol 1999;10 Suppl 4:308–11. - PubMed
    1. Ambade A, Mandrekar P. Oxidative stress and inflammation: essential partners in alcoholic liver disease. Int J Hepatol 2012;2012:853175. - PMC - PubMed

Publication types