A higher dietary ratio of long-chain omega-3 to total omega-6 fatty acids for prevention of COX-2-dependent adenocarcinomas

Nutr Cancer. 2014;66(8):1279-84. doi: 10.1080/01635581.2014.956262. Epub 2014 Oct 30.


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.

MeSH terms

  • Adenocarcinoma / prevention & control*
  • Clinical Trials as Topic
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / administration & dosage*
  • Dietary Supplements
  • Dinoprostone / metabolism
  • Docosahexaenoic Acids / administration & dosage*
  • Eicosapentaenoic Acid / administration & dosage*
  • Fatty Acids, Omega-6 / administration & dosage*
  • Fish Oils / administration & dosage
  • Humans
  • Risk Factors
  • Seafood / analysis


  • Cyclooxygenase 2 Inhibitors
  • Fatty Acids, Omega-6
  • Fish Oils
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Dinoprostone