title: The association of high-density lipoprotein cholesterol with cancer incidence in type II diabetes: a case of reverse causality?
abstract: BACKGROUND
  Low high-density lipoprotein cholesterol (HDL-C) and type II diabetes are associated with an increased risk for cancer. Patients with type II diabetes typically have low HDL-C; however, the association between HDL-C and cancer has not been examined in this population.
  
  
  METHODS
  A total of 11,140 patients with type II diabetes were followed for a median of 5 years. Cox proportional hazard models were used to assess the association between baseline HDL-C and risk of cancer incidence and cancer death, with adjustments made for potential confounders. To explore the possibility of reverse causation, analyses were repeated for the cancers occurring in the first and second halves of follow-up.
  
  
  RESULTS
  Six hundred and ninety-nine patients developed cancer, with 48% occurring within the first half of follow-up. For every 0.4 mmol/L lower baseline HDL-C, there was a 16% higher risk of cancer [HR 1.16; 95% confidence interval (CI), 1.06-1.28; P = 0.0008] and cancer death (HR 1.16; 95% CI, 1.01-1.32; P = 0.03). After adjustment for confounding, the higher risk remained significant for cancer (adjusted HR 1.10; 95% CI, 1.00-1.22; P = 0.05) but not for cancer death (adjusted HR 1.08; 95% CI, 0.93-1.25; P = 0.31). The association was driven by cancers occurring within the first half of follow-up (adjusted HR 1.22; 95% CI, 1.05-1.41; P = 0.008) as no significant association was found between HDL-C and cancer in the second half of follow-up.
  
  
  CONCLUSIONS
  Low HDL-C is associated with cancer risk in patients with type II diabetes. However, this association may be explained by confounding and reverse causation.
  
  
  CONCLUSIONS
  HDL-C is not a risk factor for cancer in type II diabetes.
authors.affiliation: The Heart Research Institute, Newtown; Sydney Medical School, University of Sydney, Camperdown, Sydney, New South Wales, Australia.
authors.forename: Jamie
authors.initials: J
authors.lastname: Morton
authors.forename: Martin K C
authors.initials: MK
authors.lastname: Ng
authors.forename: John
authors.initials: J
authors.lastname: Chalmers
authors.forename: Mark
authors.initials: M
authors.lastname: Woodward
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancia
authors.forename: Neil R
authors.initials: NR
authors.lastname: Poulter
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cooper
authors.forename: Sophia
authors.initials: S
authors.lastname: Zoungas
mesh_terms: D001315:Australia / Q000453:epidemiology; D008076:Cholesterol, HDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D007190:Indapamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000453:epidemiology; D020913:Perindopril / Q000008:administration & dosage; D016016:Proportional Hazards Models; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D008076:Cholesterol, HDL; D007190:Indapamide; D020913:Perindopril