title: A higher dietary ratio of long-chain omega-3 to total omega-6 fatty acids for prevention of COX-2-dependent adenocarcinomas.
abstract: Compelling evidence that daily low-dose aspirin decreases risk for a number of adenocarcinomas likely reflects the fact that a modest but consistent inhibition of cyclooxygenase-2 (COX-2) activity can have a meaningful protective impact on risk for such cancers. The cancer-promoting effects of COX-2 are thought to be mediated primarily by prostaglandin E2 (PGE2), synthesized from arachidonic acid. The long-chain omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), abundant in many fatty fish, can interfere with the availability of arachidonate to COX-2 by multiple complementary mechanisms; moreover, the PGE3 produced by COX-2 from EPA is a competitive inhibitor of the receptors activated by PGE2. These considerations have given rise to the hypothesis that a high dietary intake of EPA/DHA, relative to omega-6 (from which arachidonate is generated), should lessen risk for a number of adenocarcinomas by impeding PGE2 production and activity-while not posing the risk to vascular health associated with COX-2-specific nonsteroidal antiinflammatory agents. Analyses that focus on studies in which the upper category of fish consumption (not fried or salt-preserved) is 2 or more servings weekly, and on studies that evaluate the association of long-term fish oil supplementation with cancer risk yields a number of findings that are consistent with the hypothesis. Further studies of this nature may help to clarify the impact of adequate regular intakes of long-chain omega-3 on cancer risk, and perhaps provide insight into the dose-dependency of this effect.
authors.affiliation: a Mid America Heart Institute at Saint Luke's Hospital , Kansas City , Missouri , USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: DiNicolantonio
authors.forename: Mark F
authors.initials: MF
authors.lastname: McCarty
authors.forename: Subhankar
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Lavie
authors.forename: James H
authors.initials: JH
authors.lastname: O'Keefe
mesh_terms: D000230:Adenocarcinoma / Q000517:prevention & control*; D002986:Clinical Trials as Topic; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D019587:Dietary Supplements; D015232:Dinoprostone / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage*; D005395:Fish Oils / Q000008:administration & dosage; D006801:Humans; D012307:Risk Factors; D017747:Seafood / Q000032:analysis
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D043371:Fatty Acids, Omega-6; D005395:Fish Oils; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone