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Marine n-3 Fatty Acids and Colorectal Cancer: Is There a Real Link?

Department of Health Promotion and Preventive Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

Chiho Goto and Yuko Tokudome

School of Health and Human Life, Nagoya-bunri University, Inazawa, Japan

Nahomi Imaeda

Faculty of Human Life and Environmental Sciences, Nagoya Women's University, Mizuho-ku, Nagoya, Japan

Kiyonori Kuriki

Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Japan

Harumi Okuyama

Kinjogakuin University College of Pharmacy, Moriyama-ku, Nagoya, Japan

Malcolm A. Moore

APJCP Editorial Office, Asian Pacific Organization for Cancer Prevention, c/o National Cancer Institute, Bangkok, Thailand

To the Editor: Oh et al. (1) investigated the possible inverse association between consumption of fish/n-3 highly unsaturated fatty acids (HUFAs, marine omega-3 fatty acids mainly consisting of icosapentaenoic acid and docosahexaenoic acid) and the risk of colorectal cancer in the Nurses' Health Study, but failed to observe any link. However, we have documented elevated apoptosis in normal colonic membranes in Japanese patients, in the Dietary Intervention in Polypectomized Patients Study, who adhered to our regimen of high fish consumption along with fish oil and perilla oil (rich in -linolenic acid; ref. 2), suggesting a reduced risk of colorectal adenomas/tumors.

n-3 PUFAs (or n-3 HUFAs) compete with n-6 PUFAs (or arachidonic acid) in various enzymatic processes and the absolute consumption of n-3 PUFAs (or n-3 HUFAs) may be crucial for colorectal carcinogenesis (3). The median energy percentages from fish/n-3 HUFAs in the study group of Oh et al. were distributed from 0.03 to 0.18, according to quintile categorization (1), while our Japanese Dietitians' Epidemiologic Study noted a distribution of 0.26 to 0.53 (4), indicating that the quantity of fish/n-3 HUFAs consumed by Americans is only approximately one-tenth of the Japanese level. Indeed, there is no overlap with each other, the amount of the highest quintile for Americans being less than the lowest quintile for Japanese, as also discussed by the authors. Therefore, the findings in Americans, with an intake possibly insufficient to exert pharmacologic influence, may at least not be applicable to Japanese.

Furthermore, the ratio of n-6 PUFAs/n-3 PUFAs (or n-3 HUFAs) may also be critical for colorectal carcinogenesis. The intake of n-6 PUFAs by Americans is exceedingly high and their median ratios of n-3 HUFAs/n-6 PUFAs appear to be distributed from 0.006 to 0.04 (or n-6 PUFAs/n-3 HUFAs: 25.0-166.7; ref. 1), whereas those for Japanese are 0.05 to 0.11 (or n-6 PUFAs/n-3 HUFAs: 9.2-21.1; ref. 4), again with no overlap between the two populations. Plasma phospholipids in Americans would be expected to be highly saturated with n-6 PUFAs and the concentrations of n-3 HUFAs, even in the highest quintile group, might not effectively compete (5). Accordingly, we would like to stress that n-3 PUFAs and/or fish/n-3 HUFAs may indeed be favorable for the prevention of colorectal adenomas/tumors in populations, including Japanese, who consume appreciable amounts of fish and other marine foods.

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1. Oh K, Willett WC, Fuchs CS, Giovanucci E. Dietary marine n-3 fatty acids in relation to risk of distal colorectal adenoma in women. Cancer Epidemiol Biomarkers Prev 2005;14:835–41.[Abstract/Free Full Text]
2. Cheng JL, Ogawa K, Kuriki K, et al. Increased intake of n-3 polyunsaturated fatty acids elevates the level of apoptosis in the normal sigmoid colon of patients polypectomized for adenomas/tumors. Cancer Lett 2003;193:17–24.[CrossRef][Medline]
3. Kojima M, Wakai K, Tokudome S, et al. Serum levels of polyunsaturated fatty acids and risk of colorectal cancer: a prospective study. Am J Epidemiol 2005;161:462–71.[Abstract/Free Full Text]
4. Tokudome S, Imaeda N, Tokudome Y, et al. Relative validity of a semi-quantitative food frequency questionnaire versus 28 day weighed diet records in Japanese female dietitians. Eur J Clin Nutr 2001;55:735–42.[CrossRef][Medline]
5. Lands WEM, Libelt B, Morris A, et al. Maintenance of lower proportions of (n-6) eicosanoid precursors in phospholipids of human plasma in response to added dietary (n-3) fatty acids. Biochim Biophys Acta 1992;1180:147–62.[Medline]

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