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Long-chain omega-3 polyunsaturated fatty acid intake and risk of colorectal cancer.

ABSTRACT: Research suggests that long-chain omega-3 polyunsaturated fatty acids (LC-PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have antineoplastic properties, yet evidence for association between LC-PUFAs and colorectal cancer (CRC) remains inconsistent. Using the VITamins And Lifestyle (VITAL) cohort, we evaluated how EPA/DHA intake, and its primary sources, fish oil supplement use and dark fish consumption, relate to CRC risk. A total of 68,109 Washington residents aged 50-76 completed a questionnaire between 2000-2002 and were followed for CRC through 2008 (n = 488). Persons using fish oil supplements on 4+ days/wk for 3+ yr experienced 49% lower CRC risk than nonusers (hazard ratio = 0.51, 95% CI = 0.26-1.00; P trend = 0.06). The association between fish oil use and decreased CRC risk was primarily observed for men (P interaction = 0.02; P trend men = 0.02; P trend women = 0.88) and for colon cancer (P difference = 0.05; P trend colon = 0.03; P trend rectum = 0.87). Although dark fish and total EPA + DHA intake were not associated with CRC risk overall, these associations varied by genetic risk (P interaction = 0.009 and 0.02, respectively), with inverse associations observed among low-moderate genetic risk groups and positive associations observed among high risk groups. Results suggest that associations between LC-PUFA intake and CRC may vary by gender, subsite, and genetic risk, providing additional insight into the potential role of LC-PUFAs in cancer prevention.

SUBMITTER: Kantor ED

PROVIDER: S-EPMC3961554 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Long-chain omega-3 polyunsaturated fatty acid intake and risk of colorectal cancer.

Kantor Elizabeth D ED Lampe Johanna W JW Peters Ulrike U Vaughan Thomas L TL White Emily E

Nutrition and cancer 20130920 4

Research suggests that long-chain omega-3 polyunsaturated fatty acids (LC-PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have antineoplastic properties, yet evidence for association between LC-PUFAs and colorectal cancer (CRC) remains inconsistent. Using the VITamins And Lifestyle (VITAL) cohort, we evaluated how EPA/DHA intake, and its primary sources, fish oil supplement use and dark fish consumption, relate to CRC risk. A total of 68,109 Washington residents aged 50-76 comp ...[more]

PMID: 24053119

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Project description:ImportanceMarine ω-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid, possess potent immunomodulatory activity and may protect against cancer development. However, evidence relating marine ω-3 PUFAs to colorectal cancer (CRC) risk remains inconclusive.ObjectiveTo test the hypothesis that marine ω-3 PUFA intake may be associated with lower risk of CRC subsets characterized by immune infiltrate.Design, setting, and participantsThis prospective cohort study was conducted among participants in the Nurses' Health Study (1984-2010) and Health Professionals Follow-up Study (1986-2010).ExposuresIntake of marine ω-3 PUFAs.Main outcomes and measuresIncidence of CRC characterized by CD3+, CD8+, CD45RO (PTPRC)+, or FOXP3+ T-cell densities in tumor tissue, measured by immunohistochemical and computer-assisted image analysis.ResultsAmong 173 229 predominantly white participants, 125 172 with 2 895 704 person-years of follow-up provided data about marine ω-3 PUFA intake every 4 years through a validated food frequency questionnaire and followed up for incident CRC evaluation. Of 2504 CRC cases, we documented 614 (252 men, 362 women) from which we could assess T-cell infiltration in the tumor microenvironment. The inverse association of marine ω-3 PUFAs intake with CRC risk differed according to FOXP3+ T-cell infiltration: compared with intake of less than 0.15 g/d of marine ω-3 PUFAs, intake of at least 0.35 g/d was associated with a multivariable hazard ratio (HR) of 0.57 (95% CI, 0.40-0.81; P < .001 for trend) for FOXP3+ T-cell-high tumors. In contrast, the HR for FOXP3+ T-cell-low tumors was 1.14 (95% CI, 0.8-1.60) (P = .77 for trend; P = .01 for heterogeneity). No statistically significant differential association was found for high-density tumors (compared with low-density tumors) according to CD3+, CD8+, or CD45RO+ cell density (P ≥ .34 for heterogeneity for all comparisons). In functional assays, the suppressive activity of regulatory T cells was approximately 2-fold lower (T-effector-cell proliferation, ≥64% vs 38%) when preincubated with docosahexaenoic acid at 50μM, 100μM, and 200μM concentrations than without docosahexaenoic acid (P < .001 for all comparisons).Conclusions and relevanceHigh marine ω-3 PUFA intake was associated with lower risk of CRC with high-level, but not low-level, FOXP3+ T-cell density, suggesting a potential role of ω-3 PUFAs in cancer immunoprevention through modulation of regulatory T cells.

Dataset Information

Long-chain omega-3 polyunsaturated fatty acid intake and risk of colorectal cancer.

Publications

Long-chain omega-3 polyunsaturated fatty acid intake and risk of colorectal cancer.

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