Serum Lipid Levels and Colorectal Cancer Recurrence Open Access

Brantley, Kristen (2017)

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Background: Biologic and epidemiologic evidence suggests that tumor cells depend on reprogrammed lipid metabolic function for survival and growth. Mechanistically, cholesterol and triglycerides may support tumor recurrence by providing energy needed for future proliferation. Altered serum lipid profiles have been observed in cancer patients at diagnosis and throughout treatment, and studies have found associations of serum lipids with cancer incidence, mortality, and disease-free mortality. Lipids may be particularly relevant in colorectal cancer (CRC) progression, though studies have yet to evaluate the prognostic potential of serum lipids for CRC recurrence.

Methods: A prospective cohort design was used to study the effect of serum lipids, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), on CRC recurrence-free survival. The study actively followed 342 Danish colorectal cancer patients who underwent surgical resection between 2003-2011 from date of surgery until December 31, 2012, or death. Sixty patients experienced a recurrence, with a median follow-up time of 4.1 years (interquartile range [IQR] 2.3, 6.8). Serum lipids were collected at scheduled intervals throughout follow-up, and recurrence rate was assessed using Cox proportional hazards modeling. Lipids were assigned as time-varying exposures evaluated in the year preceding recurrence and models were adjusted for clinically relevant covariates. A simplified analysis was performed by excluding influence of statin use on results via censorship of patients at first prescription. All-cause and CRC-cause mortality were also assessed as outcomes of interest.

Results: Among 342 CRC patients, increased HDL-C appeared to have a beneficial impact on recurrence-free survival (RFS) for CRC patients, though protection was only observed among statin users (hazard ratio [HR]=0.80; 95% confidence interval [CI]: 0.65, 0.98). Increased LDL-C and triglycerides both had null effects on RFS. Among the subset of non-statin users (n=266) who were censored at first statin prescription, increased lipids showed a near-null effect on CRC recurrence. Triglycerides were associated with slightly decreased CRC-specific mortality among non-statin users (HR=0.83; 95% CI: 0.67, 1.01).

Conclusion: Our results suggest potential utility of HDL-C as a prognostic marker of CRC recurrence. However, small sample size and exposure-covariate relationships that are subject to time-varying confounding limits interpretation of results.

Table of Contents

Chapter I. Literature Review -------------------------1

Colorectal Cancer - Burden of Disease --------------1

Lipids in Cancer Progression and Recurrence--------6

Chapter II. Manuscript -------------------------------11

A. Abstract --------------------------------------------11

B. Introduction ---------------------------------------12

C. Methods -------------------------------------------14

D. Results --------------------------------------------20

E. Discussion -----------------------------------------26

F. References -----------------------------------------32

G. Tables ---------------------------------------------48

H. Figures --------------------------------------------53

Chapter III. Public Health Significance -------------54

Appendix. Supplementary Tables -------------------56

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