Long-term marine ω-3 polyunsaturated fatty acids intake in relation to incidence of colorectal cancer subclassified by macrophage infiltrates

Tomotaka Ugai; Juha P. Väyrynen; Satoko Ugai; Rong Zhong; Koichiro Haruki; Mai Chan Lau; Melissa Zhao; Yuxue Zhong; Qian Yao; Kosuke Matsuda; Jennifer L. Guerriero; Kai Wang; Xuehong Zhang; Andrew T. Chan; Charles S. Fuchs; Marios Giannakis; Edward L. Giovannucci; Jeffrey A. Meyerhardt; Mingyang Song; Jonathan A. Nowak; Shuji Ogino

doi:10.59717/j.xinn-med.2024.100082

The Innovation Medicine > 2024 Vol. 2 > No. 3 > 100082

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Long-term marine ω-3 polyunsaturated fatty acids intake in relation to incidence of colorectal cancer subclassified by macrophage infiltrates

1.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
2.
Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA 02115, USA
3.
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
4.
Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu 90570, Finland
5.
Department of Epidemiology and Biostatistics and Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China
6.
Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, MA 02115, USA
7.
Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
8.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
9.
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
10.
Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA
11.
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
12.
Genentech, South San Francisco, CA 94080, USA
13.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
14.
Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
15.
Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA 02115, USA
16.
Tokyo Medical and Dental University (Institute of Science Tokyo), Tokyo 113-8510, Japan
17.
These authors contributed equally
18.
These authors contributed equally

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Corresponding authors: tugai@bwh.harvard.edu (T.U.); sogino@bwh.harvard.edu (S.O.)
Received Date: April 17, 2024

Accepted Date: August 03, 2024

Published Online: August 17, 2024

The Innovation Medicine 2(3), https://doi.org/10.59717/j.xinn-med.2024.100082 | Cite this article

GRAPHICAL ABSTRACT

GRAPHICAL ABSTRACT

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. We assessed long-term intake of marine ω-3 polyunsaturated fatty acid (MOPUFA) and colorectal cancer (CRC) incidence.
  
  Higher MOPUFA intake correlated with lower incidence of CRC with scanty M1 macrophages (but not CRC with abundant M1 macrophages).
  
  The inverse association of MOPUFA intake with CRC incidence was stronger for tumors containing fewer M1 macrophages.
  
  MOPUFA may influence tumor-associated macrophages and CRC development.
  
  Dietary MOPUFA intake modifications may be used to improve cancer prevention.

ABSTRACT

ABSTRACT

Evidence indicates that marine omega-3 polyunsaturated fatty acid (MOPUFA) intake exerts an immunomodulatory effect to suppress the development of colorectal cancer (CRC). We hypothesized that the association of MOPUFA intake with the incidence of CRC might differ by macrophage infiltrates in tumor tissue. We utilized the Prospective Cohort Incident Tumor Biobank within the Nurses' Health Study and Health Professionals Follow-up Study, both of which repeatedly assessed diets for decades of the follow-up of 125,172 participants, among whom 2,959 developed incident CRC. To spatially identify and count M1-polarized and M2-polarized macrophages in tumor tissue, we conducted in situ single-cell digital image analyses using multispectral immunofluorescence [for MRC1 (CD206), MAF, IRF5, CD86, and CD68] combined with machine learning algorithms. Using the 2,959 CRC cases, inverse probability weighting was integrated into the Cox proportional hazards models to adjust for tissue macrophage data availability in 820 cases. The multivariable-adjusted hazard ratio (with 95% confidence interval) for long-term MOPUFA intake of ≥0.25 g/day (vs. <0.15 g/day) were 0.56 (0.38-0.82; P_trend = 0.004) for the incidence of CRC with the lowest-quartile M1-like macrophage density. There was no significant association of MOPUFA intake with the incidence of CRC with the second to fourth quartile M1-like macrophage densities (P_trend > 0.20). The association of MOPUFA intake with CRC incidence differed by M1-like macrophages (P_{heterogeneity} = 0.01), but not by M2-like macrophages. Our findings of the link between MOPUFA intake and lower incidence of CRC containing low M1-like macrophage counts provide evidence for differential influence of MOPUFAs on colorectal tumors with varying immune microenvironmental features.

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Ugai T., Väyrynen J., Ugai S., et al., (2024). Long-term marine ω-3 polyunsaturated fatty acids intake in relation to incidence of colorectal cancer subclassified by macrophage infiltrates. The Innovation Medicine 2(3): 100082. https://doi.org/10.59717/j.xinn-med.2024.100082

Ugai T., Väyrynen J., Ugai S., et al., (2024). Long-term marine ω-3 polyunsaturated fatty acids intake in relation to incidence of colorectal cancer subclassified by macrophage infiltrates. The Innovation Medicine 2(3): 100082. https://doi.org/10.59717/j.xinn-med.2024.100082

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Long-term marine ω-3 polyunsaturated fatty acids intake in relation to incidence of colorectal cancer subclassified by macrophage infiltrates

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Long-term marine ω-3 polyunsaturated fatty acids intake in relation to incidence of colorectal cancer subclassified by macrophage infiltrates

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