The association of high-density lipoprotein cholesterol with cancer incidence in type ii diabetes: A case of reverse causality?

Jamie Morton, Martin K C Ng, John Chalmers, Mark Woodward, Giuseppe Mancia, Neil R. Poulter, Michel Marre, Mark E. Cooper, Sophia Zoungas

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 (adjustedHR 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. Impact: HDL-C is not a risk factor for cancer in type II diabetes.

Original languageEnglish
Pages (from-to)1628-1633
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume22
Issue number9
DOIs
Publication statusPublished - Sep 2013

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Causality
Type 2 Diabetes Mellitus
HDL Cholesterol
Incidence
Neoplasms
Confidence Intervals
LDL Cholesterol
Second Primary Neoplasms
Proportional Hazards Models

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

The association of high-density lipoprotein cholesterol with cancer incidence in type ii diabetes : A case of reverse causality? / Morton, Jamie; Ng, Martin K C; Chalmers, John; Woodward, Mark; Mancia, Giuseppe; Poulter, Neil R.; Marre, Michel; Cooper, Mark E.; Zoungas, Sophia.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 22, No. 9, 09.2013, p. 1628-1633.

Research output: Contribution to journalArticle

Morton, J, Ng, MKC, Chalmers, J, Woodward, M, Mancia, G, Poulter, NR, Marre, M, Cooper, ME & Zoungas, S 2013, 'The association of high-density lipoprotein cholesterol with cancer incidence in type ii diabetes: A case of reverse causality?', Cancer Epidemiology Biomarkers and Prevention, vol. 22, no. 9, pp. 1628-1633. https://doi.org/10.1158/1055-9965.EPI-13-0149
Morton, Jamie ; Ng, Martin K C ; Chalmers, John ; Woodward, Mark ; Mancia, Giuseppe ; Poulter, Neil R. ; Marre, Michel ; Cooper, Mark E. ; Zoungas, Sophia. / The association of high-density lipoprotein cholesterol with cancer incidence in type ii diabetes : A case of reverse causality?. In: Cancer Epidemiology Biomarkers and Prevention. 2013 ; Vol. 22, No. 9. pp. 1628-1633.
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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 (adjustedHR 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. Impact: HDL-C is not a risk factor for cancer in type II diabetes.",
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T1 - The association of high-density lipoprotein cholesterol with cancer incidence in type ii diabetes

T2 - A case of reverse causality?

AU - Morton, Jamie

AU - Ng, Martin K C

AU - Chalmers, John

AU - Woodward, Mark

AU - Mancia, Giuseppe

AU - Poulter, Neil R.

AU - Marre, Michel

AU - Cooper, Mark E.

AU - Zoungas, Sophia

PY - 2013/9

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N2 - 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 (adjustedHR 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. Impact: HDL-C is not a risk factor for cancer in type II diabetes.

AB - 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 (adjustedHR 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. Impact: HDL-C is not a risk factor for cancer in type II diabetes.

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