Eicosanoid profiling in colon cancer: Emergence of a pattern

Oxidative metabolism of polyunsaturated fatty acids has been linked to tumorigenesis in general and colonic tumorigenesis in particular. Earlier studies showed that cyclooxygenase-2 (COX-2) and 15-lipoxygenase-1 (15-LOX-1) have opposing impacts on colonic tumorigenesis: COX-2 promotes while 15-LOX-1 inhibits colonic tumorigenesis. Advances in liquid chromatography/mass spectrometry have allowed for measurement of various products of oxidative metabolism in a single colonic biopsy specimen. Studies of LOX products in preclinical models and in patients with familial adenomatous polyposis and sporadic colorectal tumorigenesis indicate that LOX pathways are shifted during colonic tumorigenesis and that the main shift is downregulation of 15-LOX-1. This shift occurs during the polyp formation stage and thus offers the opportunity to modulate tumorigenesis early by correcting 15-LOX-1 downregulation.

► N-6 PUFA oxidative metabolism via cyclooxygenases and lipoxygenases modulates colorectal tumorigenesis.
► COX-2 is upregulated and 15-LOX-1 is downregulated during colorectal tumorigenesis.
► 15-LOX-1 downregulation is the primary lipoxygenase shift during colorectal tumorigenesis.