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Review |

Effects of Omega-3 Fatty Acids on Cancer Risk:  A Systematic Review

Catherine H. MacLean, MD, PhD; Sydne J. Newberry, PhD; Walter A. Mojica, MD, MPH; Puja Khanna, MD; Amalia M. Issa, MPH, PhD; Marika J. Suttorp, MS; Yee-Wee Lim, MD, PhD; Shana B. Traina, MA; Lara Hilton, BA; Rena Garland, BA; Sally C. Morton, PhD
JAMA. 2006;295(4):403-415. doi:10.1001/jama.295.4.403.
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Context Omega-3 fatty acids are purported to reduce the risk of cancer. Studies have reported mixed results.

Objective To synthesize published and unpublished evidence to determine estimates of the effect of omega-3 fatty acids on cancer risk in prospective cohort studies.

Data Sources Articles published from 1966 to October 2005 identified through MEDLINE, PREMEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and CAB Health; unpublished literature sought through letters to experts in the neutraceutical industry.

Study Selection A total of 38 articles with a description of effects of consumption of omega-3 fatty acids on tumor incidence, prospective cohort study design, human study population; and description of effect of omega-3 among groups with different levels of exposure in the cohort were included. Two reviewers independently reviewed articles using structured abstraction forms; disagreements were resolved by consensus.

Data Extraction Two reviewers independently abstracted detailed data about the incidence of cancer, the type of cancer, the number and characteristics of the patients, details on the exposure to omega-3 fatty acids, and the elapsed time between the intervention and outcome measurements. Data about the methodological quality of the study were also abstracted.

Data Synthesis Across 20 cohorts from 7 countries for 11 different types of cancer and using up to 6 different ways to categorize omega-3 fatty acid consumption, 65 estimates of the association between omega-3 fatty acid consumption were reported. Among these, only 8 were statistically significant. The high degree of heterogeneity across these studies precluded pooling of data. For breast cancer 1 significant estimate was for increased risk (incidence risk ratio [IRR], 1.47; 95% confidence interval [CI], 1.10-1.98) and 3 were for decreased risk (RR, 0.68-0.72); 7 other estimates did not show a significant association. For colorectal cancer, there was 1 estimate of decreased risk (RR, 0.49; 95% CI, 0.27-0.89) and 17 estimates without association. For lung cancer one of the significant associations was for increased cancer risk (IRR, 3.0; 95% CI, 1.2-7.3), the other was for decreased risk (RR, 0.32; 95% CI, 0.13-0.76), and 4 other estimates were not significant. For prostate cancer, there was 1 estimate of decreased risk (RR, 0.43; 95% CI, 0.22-0.83) and 1 of increased risk (RR, 1.98; 95% CI, 1.34-2.93) for advanced prostate cancer; 15 other estimates did not show a significant association. The study that assessed skin cancer found an increased risk (RR, 1.13; 95% CI, 1.01-1.27). No significant associations between omega-3 fatty acid consumption and cancer incidence were found for aerodigestive cancer, bladder cancer, lymphoma, ovarian cancer, pancreatic cancer, or stomach cancer.

Conclusions A large body of literature spanning numerous cohorts from many countries and with different demographic characteristics does not provide evidence to suggest a significant association between omega-3 fatty acids and cancer incidence. Dietary supplementation with omega-3 fatty acids is unlikely to prevent cancer.

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Figure 1. Literature Flow to Assess the Effects of Omega-3 Fatty Acid on Tumor Incidence
Graphic Jump Location
Figure 2. Risk of Developing Cancer for Participants in the Highest Grouping vs Those in the Lowest Grouping of Omega-3 Fatty Acid Intake by Cancer Type
Graphic Jump Location

Because variance and sample size are approximately inversely related, the point estimates for studies with larger sample sizes are represented with larger boxes and the point estimates for studies with smaller sample sizes are represented with smaller boxes on the plots.

Figure 3. Risk of Developing Cancer for Participants in the Highest Grouping vs Those in the Lowest Grouping of Omega-3 Fatty Acid Intake by Omega-3 Fatty Acid Type
Graphic Jump Location

Because variance and sample size are approximately inversely related, the point estimates for studies with larger sample sizes are represented with larger boxes and the point estimates for studies with smaller sample sizes are represented with smaller boxes on the plots.

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