title: Increased risk of gastrointestinal malignancy in patients with diabetes mellitus and correlations with anti-diabetes drugs: a nationwide population-based study in Taiwan.
abstract: OBJECTIVE
  Although the major cause of morbidity and mortality in patients with diabetes mellitus (DM) is cardiovascular disease, DM is also associated with certain site-specific cancers. However, whether DM is associated with an increased risk of cancer of the digestive tract remains undetermined. A nationwide, population-based database in Taiwan was analyzed to explore the relationship between DM and cancer of the digestive organs.
  
  
  METHODS
  From 2000 to 2007, a study cohort consisting of 39,515 patients with newly diagnosed diabetes without a previous diagnosis of gastrointestinal (GI) cancer was identified from the National Health Insurance Research Database in Taiwan. A control cohort of 79,030 age- and sex-matched non-diabetic subjects was selected to compare the occurrence of GI malignancies between the two groups. The association between the incidence of GI cancers and the use of glucose-lowering therapies was also investigated.
  
  
  RESULTS
  During the 7-year follow-up period, GI cancers developed in 929 diabetic patients (2.35%) and 1,126 subjects (1.42%) in the comparison cohort. DM was associated with a 2.75-fold (95% confidence interval (CI), 2.51-3.02) higher risk of developing GI malignancy. Among GI cancers, the incidences of stomach (adjusted hazard ratio (HR), 1.49; 95% CI, 1.16-1.92), liver (adjusted HR, 2.65; 95% CI, 2.29-3.07), colon (adjusted HR, 1.58; 95% CI, 1.28-1.94) and pancreatic cancers (adjusted HR, 4.35; 95% CI, 2.93-6.47) were significantly increased in the patients with DM. An analysis of the effects of various glucose-lowering therapies in the diabetic patients revealed the use of α-glucosidase inhibitors to be associated with a lower risk of hepatic cancer (adjusted HR, 0.62; 95% CI, 0.4-0.94). Thiazolidinedione (TZD) treatment was associated with lower stomach (adjusted HR, 0.11; 95% CI, 0.02-0.82) and hepatic cancer risks (adjusted HR, 0.46; 95% CI, 0.29-0.73), while sulfonylurea use was associated with a lower colon cancer risk (adjusted HR, 0.74; 95% CI, 0.51-1.09) and a higher pancreatic cancer risk (adjusted HR, 2.36; 95% CI, 1.21-4.61).
  
  
  CONCLUSIONS
  Patients with DM have an increased risk of GI malignancy that may be affected by the use of different categories of glucose-lowering therapies.
authors: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taiwan.
authors: Chun-Chih
authors: CC
authors: Chiu
authors: Chin-Chou
authors: CC
authors: Huang
authors: Yu-Chun
authors: YC
authors: Chen
authors: Tzeng-Ji
authors: TJ
authors: Chen
authors: Ying
authors: Y
authors: Liang
authors: Shing-Jong
authors: SJ
authors: Lin
authors: Jaw-Wen
authors: JW
authors: Chen
authors: Hsin-Bang
authors: HB
authors: Leu
authors: Wan-Leong
authors: WL
authors: Chan
mesh_terms: D001645:Biguanides / Q000627:therapeutic use; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000453:epidemiology*; D004067:Digestive System Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000517:prevention & control; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000145:classification / Q000627:therapeutic use; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D016016:Proportional Hazards Models; D012494:Sampling Studies; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use; D013624:Taiwan / Q000453:epidemiology; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use; D000520:alpha-Glucosidases / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D001645:Biguanides; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D000520:alpha-Glucosidases