Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Department of Population Health, New York University School of Medicine, New York, NY, USA. Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA. Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. Slone Epidemiology Center at Boston University, Boston, MA, USA. Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, USA. Department of Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington, DC, USA. Division of Pediatric Epidemiology and Clinical Research and Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA. Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA. VA Boston Healthcare System, Boston, MA, USA. Division of Medical Oncology, National Cancer Centre, Singapore, Singapore. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Am J Gastroenterol. 2018 Oct;113(10):1494-1505. doi: 10.1038/s41395-018-0207-4. Epub 2018 Sep 3.
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.
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.
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; I = 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 (I = 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.
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.
肥胖和糖尿病与肝癌风险增加相关。然而，大多数研究都检查了所有原发性肝癌或肝细胞癌，很少有研究评估肝内胆管癌（ICC），这是第二种最常见的肝癌。因此，我们在汇总分析中研究了肥胖和糖尿病与 ICC 风险之间的关系，并对文献进行了系统评价/荟萃分析。
对于汇总分析，我们利用了由 13 个基于美国的前瞻性队列研究组成的肝癌汇总项目（LCPP），该项目的数据来自 1541143 个人（ICC 病例 n=414）。在我们的系统评价中，我们确定了另外 14 项研究。然后，我们进行了荟萃分析，将 LCPP 的结果与截至 2017 年 9 月通过 5 项前瞻性研究确定的结果相结合。
在 LCPP 中，肥胖和糖尿病与 ICC 风险分别增加 62%（风险比 [HR] = 1.62，95%置信区间 [CI]：1.24-2.12）和 81%（HR = 1.81，95% CI：1.33-2.46）。在前瞻性确定的队列和巢式病例对照研究的荟萃分析中，肥胖与 ICC 风险增加 49%相关（相对风险 [RR] = 1.49，95% CI：1.32-1.70；n=4 项研究；I=0%）。糖尿病与 ICC 风险增加 53%相关（RR = 1.53，95% CI：1.31-1.78；n=6 项研究）。虽然我们注意到糖尿病研究之间存在异质性（I=67%），但亚组分析的结果一致。来自基于医院的病例对照研究（n=9）的结果基本一致，但这些研究可能受到反向因果关系的影响。
这些发现表明肥胖和糖尿病与 ICC 风险增加相关，突出了肝细胞癌和肝内胆管癌的相似病因。然而，需要更多的前瞻性研究来验证这些关联。
