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.
Bibliographical noteFunding Information:
revision of the manuscript for important intellectual content: AL Van Dyke, J Koshiol, BI Graubard; design and collection data from individual cohort studies, design of the consortium, interpretation of data, and critical revision of the manuscript for important intellectual content: A Zeleniuch-Jacquotte, X Zhang, J Wactawski-Wende, MJ Stamp-fer, R Sinha, HD Sesso, C Schairer, L Rosenberg, TE Rohan, K Robien, MP Purdue, JN Poynter, JR Palmer, CC Newton, MS Linet, LM Liao, IM Lee, CM Kitahara, JN Hofmann, E Giovannucci, JM Gaziano, SM Gapstur, ND Freedman, DQ Chong, AT Chan, JE Buring, LE Beane Freeman, PT Campbell; concept and design of the consortium, collection of data for the consortium, analysis and interpretation of data, and critical revision of the manuscript for important intellectual content: KA McGlynn. All authors approved the final draft submitted. Financial support: NIH Intramural Research Program, National Cancer Institute (JL Petrick, JE Thistle, LE Beane Freeman, JN Hofmann, CM Kitahara, ND Freedman, BI Graubard, J Koshiol, LM Liao, MS Linet, MP Purdue, C Schairer, R Sinha, AL Van Dyke, KA McGlynn). National Institutes of Health grants CA047988 (I Lee, JE Buring), HL043851 (I Lee, JE Buring), HL080467 (I Lee, JE Buring), HL099355 (I Lee, JE Buring), DK098311 (AT Chan), CA186107 (AT Chan), CA87969 (AT Chan), CA167552 (AT Chan), UM1 CA164974 (L Rosenberg, JR Palmer), and R01 CA058420 (L Rosenberg, JR Palmer). The WHI program (J Wactawski-Wende, TE Rohan) is funded by the National Institutes of Health contracts HHSN268201600018C, HHSN268201600001C, HHSN26820 1600002C, HHSN268201600003C, and HHSN268201600004C. Potential competing interests: None.
© 2018, American College of Gastroenterology.