Interactive role of diabetes mellitus and female sex in the risk of cholangiocarcinoma: A population-based nested case-control study

// Yan-Jiun Huang 1, 2 , Alexander TH Wu 2 , Hung-Yi Chiou 5 , Ming-Tsang Chuang 5 , Tzu-Ching Meng 6 , Li-Nien Chien 4, * , Yun Yen 2, 3, * 1 Department of Surgery, Division of Colorectal Surgery, Taipei Medical University Hospital, Taipei, Taiwan 2 The Ph.D. Program for Translational Medicine, Taipei Medical University & Academia Sinica, Taipei, Taiwan 3 Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan 4 School of Health Care Administration, College of Management, Taipei Medical University, Taipei, Taiwan 5 School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan 6 Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Yun Yen, email: yyen@tmu.edu.tw Li-Nien Chien, email: lnchien@tmu.edu.tw Keywords: cholangiocarcinoma, diabetes, population-based, intrahepatic, extrahepatic Received: October 26, 2016      Accepted: November 30, 2016      Published: December 27, 2016 ABSTRACT Diabetes mellitus (DM) has been associated with an increased risk of extrahepatic cholangiocarcinoma (ECC) and intrahepatic cholangiocarcinoma (ICC). However, the role of DM in a population with a lower incidence of ECC remains unclear. We investigated the role of DM and other risk factors for ECC and ICC by conducting a population-based, nested, case–control study in Taiwan, a region with a lower incidence but a higher proportion of ICC. We identified patients who received a diagnosis of cholangiocarcinoma (CC) from the Taiwan Cancer Registry between 2003 and 2009. A total of 6,093 CC cases (ICC: 4,695; ECC: 1,396) and 60,906 matched controls were included. Compared with the controls, the patients with ICC and ECC were more likely to have DM, with an adjusted OR of 1.22 [95% confidence interval (CI): 1.07–1.39] and 1.48 (95% CI: 1.18–1.85), respectively. DM was associated with an increased risk of CC in the women and patients without a history of biliary tract diseases. Moreover, compared with the controls, DM was not associated with an increased risk of ECC in the patients who received cholecystectomy. These findings strongly support the positive association between DM and the increased risk of both ICC and ECC; however, this association was not observed in the patients who received cholecystectomy.