title: Association between Gastroenterological Malignancy and Diabetes Mellitus and Anti-Diabetic Therapy: A Nationwide, Population-Based Cohort Study.
abstract: BACKGROUND
  The relationship between diabetes mellitus (DM) and cancer incidence has been evaluated in limited kinds of cancer. The effect of anti-diabetic therapy (ADT) on carcinogenesis among diabetic patients is also unclear.
  
  
  METHODS
  Using population-based representative insurance claims data in Taiwan, 36,270 DM patients and 145,080 comparison subjects without DM were identified from claims from 2005 to 2010. The association between the top ten leading causes of cancer-related death in Taiwan and DM was evaluated. Whether ADT altered the risk of developing cancer was also investigated.
  
  
  RESULTS
  Incidence of cancer at any site was significantly higher in patients with DM than in those without (p<0.001). The risk of carcinogenesis imparted by DM was greatest in gastroenterological malignancies (liver, pancreas, and colorectal cancer) as well as lung, breast and oral cancer (p<0.001). Among the oral types of ADT, metformin decreased the risk of lung and liver cancer, but had less effect on reducing the risk of colorectal cancer. α-glucosidase inhibitor decreased the risk of developing liver, colorectal, and breast cancer. Apart from intermediate-acting insulin, rapid-acting, long-acting, and combination insulin treatment significantly reduced the overall cancer risk among all DM patients. In subgroup analysis, long-acting insulin treatment significantly decreased the risk of lung, liver, and colorectal cancer.
  
  
  CONCLUSIONS
  Our results supported the notion that pre-existing DM increases the incidence of gastroenterological cancer. ADT, especially metformin, α-glucosidase inhibitor, and long-acting insulin treatment, may protect patients with DM against these malignancies. It is crucial that oncologists should closely collaborate with endocrinologists to provide an optimal cancer-specific therapy and diabetic treatment to patients simultaneously with cancer and DM.
authors.affiliation: Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chien-Ming
authors.initials: CM
authors.lastname: Lin
authors.affiliation: Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan; Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Huang
authors.affiliation: Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Fang-Ying
authors.initials: FY
authors.lastname: Chu
authors.affiliation: Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Hueng-Chuen
authors.initials: HC
authors.lastname: Fan
authors.affiliation: Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Hung-An
authors.initials: HA
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Der-Ming
authors.initials: DM
authors.lastname: Chu
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Family and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Wu
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Family and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chung-Ching
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Family and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Wei-Liang
authors.initials: WL
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shih-Hua
authors.initials: SH
authors.lastname: Lin
authors.affiliation: Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan; Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Shinn-Ying
authors.initials: SY
authors.lastname: Ho
mesh_terms: D000328:Adult; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000209:etiology; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000453:epidemiology*; D005260:Female; D065089:Glycoside Hydrolase Inhibitors / Q000009:adverse effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D015994:Incidence; D049528:Insulin, Long-Acting / Q000009:adverse effects; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008687:Metformin / Q000009:adverse effects; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000453:epidemiology* / Q000209:etiology; D012189:Retrospective Studies; D013624:Taiwan; D055815:Young Adult
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D008687:Metformin