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Independent associations between low-density lipoprotein cholesterol and cancer among patients with type 2 diabetes mellitus

From the Department of Medicine and Therapeutics (Yang, So, Ma, Kong, Chow, Tong), the Hong Kong Institute of Diabetes and Obesity (Ko, Tong, Chan), and the Li Ka Shing Institute of Health Sciences (Kong, Chan), The Chinese University of Hong Kong, Hong Kong, China

Correspondence to: Prof. Juliana C.N. Chan, 9/F Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China; fax 852 2632 3108; jchan{at}cuhk.edu.hk

Background: The risk association between low-density lipoprotein (LDL) cholesterol and cancer remains controversial and largely unexplored for people not receiving statin therapy.

Methods: We examined the risk association between LDL cholesterol and cancer among patients with type 2 diabetes mellitus who were free of cancer at enrolment and whose statin use was known. We considered a variety of nonlinear relationships in our analysis.

Results: During a median follow-up period of 4.90 years, cancer developed in 270 (4.4%) of 6107 patients. Among the 3800 patients who did not receive statin therapy, the risk association between LDL cholesterol and cancer was represented by a V-shaped curve. Compared with patients whose LDL cholesterol was at least 2.80 mmol/L but less than 3.80 mmol/L, the risk of cancer, death from any cause or the composite outcome of cancer or death was greater among those with an LDL cholesterol level of less than 2.80 mmol/L (hazard ratio for cancer 1.74, 95% confidence interval [CI] 1.20–2.52) and those with an LDL cholesterol level of 3.80 mmol/L or greater (hazard ratio for cancer 1.87, 95% CI 1.29–2.71). Using 3.8 mmol/L as a reference point, we found that the hazard ratio for cancer for every millimole per litre absolute change in LDL cholesterol was 1.54 (95% CI 1.19–1.99) among patients not using statins; the hazard ratio was reduced to 1.24 (1.01–1.53) for the entire sample (statin users and those not using statins). These associations persisted after adjustment for covariates and exclusion of patients with less than 2.5 years of follow-up.

Interpretation: Among patients with type 2 diabetes, the association between LDL cholesterol and cancer was V-shaped, whereby both low and high levels of LDL cholesterol were associated with elevated risk of cancer.

This article has been cited by other articles:

				X. Yang, W. Y. So, R. C.W. Ma, G. T.C. Ko, A. P.S. Kong, H. Zhao, A. O.Y. Luk, C. W.K. Lam, C. S. Ho, P. C.Y. Tong, et al. Low LDL Cholesterol, Albuminuria, and Statins for the Risk of Cancer in Type 2 Diabetes: The Hong Kong Diabetes Registry Diabetes Care, October 1, 2009; 32(10): 1826 - 1832. [Abstract] [Full Text] [PDF]

				X. Yang, H. Zhao, Y. Sui, R. C.W. Ma, W. Y. So, G. T.C. Ko, A. P.S. Kong, R. Ozaki, C. Y. Yeung, G. Xu, et al. Additive Interaction Between the Renin-Angiotensin System and Lipid Metabolism for Cancer in Type 2 Diabetes Diabetes, July 1, 2009; 58(7): 1518 - 1525. [Abstract] [Full Text] [PDF]

				G. T.C. Ko, W.-Y. So, P. C. Tong, W.-B. Chan, X. Yang, R. C. Ma, A. P. Kong, R. Ozaki, C.-Y. Yeung, C.-C. Chow, et al. Effect of interactions between C peptide levels and insulin treatment on clinical outcomes among patients with type 2 diabetes mellitus Can. Med. Assoc. J., April 28, 2009; 180(9): 919 - 926. [Abstract] [Full Text] [PDF]

				E. L. Ding ScD and F. B. Hu MD PhD Cancer and cholesterol: understanding the V-shaped association in patients with diabetes Can. Med. Assoc. J., August 26, 2008; 179(5): 403 - 404. [Full Text] [PDF]

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