Does the lipid-lowering peroxisome proliferator-activated receptors ligand bezafibrate prevent colon cancer in patients with coronary artery disease?
BACKGROUND
Epidemiologic studies have suggested that hypertriglyceridemia and insulin resistance are related to the development of colon cancer. Nuclear peroxisome proliferator-activated receptors (PPAR), which play a central role in lipid and glucose metabolism, had been hypothesized as being involved in colon cancerogenesis. In animal studies the lipid-lowering PPAR ligand bezafibrate suppressed colonic tumors. However, the effect of bezafibrate on colon cancer development in humans is unknown. Therefore, we proposed to investigate a possible preventive effect of bezafibrate on the development of colon cancer in patients with coronary artery disease during a 6-year follow-up.


METHODS
Our population included 3011 patients without any cancer diagnosis who were enrolled in the randomized, double blind Bezafibrate Infarction Prevention (BIP) Study. The patients received either 400 mg of bezafibrate retard (1506 patients) or placebo (1505 patients) once a day. Cancer incidence data were obtained by matching a subject's identification numbers with the National Cancer Registry. Each matched record was checked for correct identification.


RESULTS
Development of new cancer (all types) was recorded in 177 patients: in 79 (5.25%) patients from the bezafibrate group vs. 98 (6.51%) from the placebo group. Development of colon cancer was recorded in 25 patients: in 8 (0.53%) patients from the bezafibrate group vs. 17 (1.13%) from the placebo group, (Fisher's exact test: one side p = 0.05; two side p = 0.07). A difference in the incidence of cancer was only detectable after a 4 year lag and progressively increased with continued follow-up. On multivariable analysis the colon cancer risk in patients who received bezafibrate tended to be lower with a hazard ratio of 0.47 and 95% confidence interval 0.2-1.1.


CONCLUSIONS
Our data, derived from patients with coronary artery disease, support the hypothesis regarding a possible preventive effect of bezafibrate on the development of colon cancer.
Cardiac Rehabilitation Institute, Chaim Sheba Medical Center, Tel-Hashomer, affiliated with Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. altenen@post.tau.ac.il
Alexander
A
Tenenbaum
Valentina
V
Boyko
Enrique Z
EZ
Fisman
Ilan
I
Goldenberg
Yehuda
Y
Adler
Micha S
MS
Feinberg
Michael
M
Motro
David
D
Tanne
Joseph
J
Shemesh
Ehud
E
Schwammenthal
Solomon
S
Behar
D000368:Aged; D001629:Bezafibrate / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000517:prevention & control*; D003324:Coronary Artery Disease / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008024:Ligands; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D047492:Peroxisome Proliferator-Activated Receptors / Q000037:antagonists & inhibitors*; D016032:Randomized Controlled Trials as Topic
D000960:Hypolipidemic Agents; D008024:Ligands; D047492:Peroxisome Proliferator-Activated Receptors; D001629:Bezafibrate