Blood levels of long-chain polyunsaturated fatty acids, aspirin, and the risk of colorectal cancer

Cancer Epidemiol Biomarkers Prev. 2007 Feb;16(2):314-21. doi: 10.1158/1055-9965.EPI-06-0346.


Background: N-3 fatty acids may decrease risk of colorectal cancer by inhibiting the cyclooxygenase-2 enzyme and production of proinflammatory eicosanoids derived from arachidonic acid (20:4n-6). Aspirin also inhibits the cyclooxygenase-2 enzyme and may share with n-3 fatty acids a potential mechanism to decrease the risk of colorectal cancer.

Methods: We conducted a nested case-control analysis using blood samples collected from the Physicians' Health Study participants in 1982 to 1984. N-3 and n-6 fatty acid levels were measured using gas-liquid chromatography for 178 men who developed colorectal cancer through December 31, 1995 and 282 age- and smoking-matched controls. We used conditional logistic regression to examine associations. All statistical tests were two-sided.

Results: Total long-chain n-3 fatty acids were nonsignificantly inversely associated with colorectal cancer risk [relative risk (RR) for highest versus lowest quartile, 0.60; 95% confidence interval (95% CI), 0.32 to 1.11; P(trend) = 0.10], after adjustment for possible confounders. We observed potential interaction between randomized aspirin assignment and long-chain n-3 fatty acid levels (P(interaction) = 0.04). Among men not on aspirin, RRs (95% CI) for increasing quartiles of long-chain n-3 fatty acids were 1.00 (reference), 0.60 (0.28-1.28), 0.51 (0.22-1.17), and 0.34 (0.15-0.82), P(trend) = 0.006. For participants taking aspirin, there was no additional benefit of increasing n-3 fatty acid levels. The RR (95% CI) for the highest versus lowest quartile of n-6 fatty acids was 0.64 (0.35-1.17).

Conclusions: Blood levels of long-chain n-3 fatty acids were associated with decreased risk of colorectal cancer among men not using aspirin. N-6 fatty acids were nonsignificantly inversely associated with colorectal cancer risk.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Aspirin / administration & dosage*
  • Aspirin / pharmacology
  • Cardiovascular Diseases / prevention & control
  • Case-Control Studies
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / prevention & control
  • Fatty Acids, Omega-3 / blood*
  • Fatty Acids, Omega-6 / blood*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Neoplasms / prevention & control
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Risk
  • Risk Factors
  • Surveys and Questionnaires


  • Anti-Inflammatory Agents, Non-Steroidal
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Aspirin