• Prévention

  • Nutrition et prévention

  • Colon-rectum

Marine omega-3 polyunsaturated fatty acid intake and risk of colorectal cancer characterized by tumor-infiltrating t cells

Menée aux Etats-Unis à partir de questionnaires auprès de 125 152 participants (durée de suivi : 2 895 704 personnes-années), cette étude évalue l'association entre un régime alimentaire riche en acides gras oméga-3 polyinsaturés ayant pour origine des produits de la mer et le risque de cancer colorectal selon le sous-type de lymphocytes T infiltrant la tumeur

Importance : Marine

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. Objective

:

To 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 Participants

:

This prospective cohort study was conducted among participants in the Nurses

’ Health Study (1984-2010) and Health Professionals Follow-up Study (1986-2010). Exposures : Intake of marine

ω-3 PUFAs. Main Outcomes and Measures

:

Incidence of CRC characterized by CD3+, CD8+, CD45RO (PTPRC)+, or FOXP3+ T-cell densities in tumor tissue, measured by immunohistochemical and computer-assisted image analysis. Results

:

Among 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 50

μM, 100μM, and 200μM concentrations than without docosahexaenoic acid (P

 < .001 for all comparisons). Conclusions and Relevance : High 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.

JAMA Oncology

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