Original article
Alimentary tract
Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort

https://doi.org/10.1016/j.cgh.2019.06.031Get rights and content

Background & Aims

There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Methods

Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs.

Results

Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80–0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82–0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83–1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78–0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18–1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026).

Conclusions

In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.

Section snippets

Study Participants

EPIC is a prospective cohort of 521,324 participants, recruited between 1992 and 2000 in 23 centers located in 10 European countries (Denmark, France, Germany, Greece, Italy, Netherlands, Norway, Spain, Sweden, and United Kingdom).19 Anthropometric measures, lifestyle, and dietary intake were collected at recruitment. Blood samples were also collected and stored at the International Agency for Research on Cancer (IARC) or in local biobanks. Ethical approval was obtained from the review boards

Results

After a median follow-up time of 14.9 years, 6291 incident cases of CRC (2719 men and 3572 women) were diagnosed. Of these cases, 4197 were colon cancers, whereas 2094 cases were rectal cancer cases. Compared with non-cases, cases were more likely to be current or former smokers and higher consumers of red and processed meats and alcohol (Table 1).

Discussion

In this prospective analysis of approximately half a million participants, we found that intakes of total fish including fatty fish, lean fish, and shellfish were inversely associated with CRC risk. Overall, weekly intake of 100–200 g of fatty or lean fish was associated with 7% lower CRC risk. Similarly, dietary intakes of all n-3 LC-PUFAs were inversely associated with the risk for CRC, whereas the n-6:n-3 LC-PUFA ratio was positively associated with CRC. On the other hand, circulating levels

Acknowledgments

The authors thank the EPIC study participants and staff for their valuable contribution to this research. The authors would also like to thank Mr Bertrand Hemon and Ms Carine Biessy for their support in preparing the databases and providing technical support pertaining to the data analysis.

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    Conflicts of interest The authors disclose no conflicts.

    Funding Supported by a grant from the World Cancer Research Fund (WCRF) to Marc Gunter (grant number: WCRF 2013/1002). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), and Federal Ministry of Education and Research (BMBF) (Germany); Hellenic Health Foundation, Stavros Niarchos Foundation, and the Hellenic Ministry of Health and Social Solidarity (Greece); Italian Association for Research on Cancer (AIRC), National Research Council, and Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS) Ragusa, Associazione Volontari Italiani Sangu (AVIS) Ragusa, Sicilian Government (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands); Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and the Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública and Instituto de Salud Carlos II (ISCIII RETIC) (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, the Wellcome Trust (UK), Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).

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