Short Communication Fatty Fish Consumption Lowers the Risk of Endometrial Cancer: A Nationwide Case-Control Study in Sweden 1 Paul Terry, 2 Alicja Wolk, Harri Vainio, and Elisabete Weiderpass Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden [P. T., A. W., E. W.]; Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, Bronx, New York [P. T.]; and International Agency for Research on Cancer (IARC), Lyon, France [H. V.] Abstract The consumption of fatty fish, which contains large amounts of omega-3 fatty acids, may lower the risk of hormone- responsive cancers. Our aim was to study the association of fish consumption and endometrial cancer risk in Sweden, a country with a wide range of high fatty fish consumption. Using data from a large, nationwide case-control study (709 cases and 2888 controls), we analyzed consumption of both fatty (e.g., salmon and herring) and lean (e.g., cod and flounder) fish in relation to endometrial cancer risk, adjusting estimates for a wide range of potentially confounding variables. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from unconditional logistic regression models fit by maximum likelihood methods. Consumption of fatty fish was inversely associated with endometrial cancer risk. The multivariate OR for women in the highest quartile level (median, 2.0 servings per week), compared to women with in the lowest (median, 0.2 servings per week), was 0.6 (95% CI, 0.5– 0.8; P for trend, 0.0002). The corresponding OR for women in the highest quartile level of lean fish (median, 2.5 servings per week), compared to women in the lowest (median, 0.6 servings per week), was 1.0 (95% CI, 0.8 –1.3; P-value for trend, 0.72). Total fish consumption was inversely associated with risk, although weakly. Our results suggest that the consumption of fatty fish, but not other types of fish, may decrease the risk of endometrial cancer. Introduction A recent cross-sectional study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort in 16 regions of Europe showed significantly increased (3- to 4-fold) plasma levels of EPA, 3 an omega-3 fatty acid, in people from Sweden and Denmark with high consumption levels of fatty fish (1). EPA competes with arachidonic acid as substrate for cyclooxygenases, and, therefore, high concentrations of EPA can lead to important changes in relative concentrations of tumor growth-enhancing prostaglandins (2, 3). In Sweden, for example, a recent cohort study of 6272 men found that high fish consumption was associated with a significant reduction in prostate cancer incidence and mortality (4). Although omega-3 fatty acids contained in fatty fish have been shown to retard the growth of hormone-responsive tumors in vitro and in animal experiments (2, 3), evidence from studies of hormone-responsive cancers conducted among human populations remains sparse. Regarding endometrial cancer, five case-control studies (5–9) and one prospective cohort study (10) of total fish consumption have found mixed results. However, none of these studies have specifically examined the consumption of fatty fish or omega-3 fatty acids in relation to risk. Null results are not surpris- ing in populations with a low range of total fish consumption, especially if the percentage of fatty fish is also low. Therefore, we examined the association between the consumption of fatty fish, lean fish, and endometrial cancer in a nationwide case-control study of women in Sweden, a country with a relatively wide range of fatty fish consumption (11). Materials and Methods The methods of this population-based case-control study have been described elsewhere (12). In brief, the study was con- ducted among postmenopausal women ages 50 –74 years, born in Sweden and residing in Sweden from 1994 through 1995. Eligible as case patients (n = 1055) were women with an incident, primary, endometrial cancer, identified through six regional cancer registries in Sweden. Control women (n = 4216) were randomly selected from a continuously updated population register. Participation rates were 75% among case patients (789 of 1055 eligible) and 79.9% among the control women (3368 of 4216 eligible). Histological specimens for case women were reviewed by the study pathologist (Anders Lindgren) who, blinded to any characteristics of the subjects, reclassified 80 cases as endometrial atypical hyperplasia, which we excluded from the analysis. Data were obtained through mailed questionnaires. Partic- ipants were asked how often per day, per week, or per month, on average, 1 year prior to the interview, they had consumed different types of fish and 32 other foods, using nine predefined frequency categories that ranged from “never/seldom” to “three or more times per day.” The questionnaire also covered hor- mone replacement therapy (12), reproductive and medical his- tories, anthropometrical measures, and lifestyle factors such as physical activity, smoking, and multivitamin use. Among control subjects, 480 (14.3%) of 3368 failed to return the mailed questionnaire but agreed to a telephone in- terview including most questionnaire items (except family his- tory of cancer, diet, alcohol consumption, and medical history). These controls were excluded from the present analysis. An additional 36 controls (1.2%), and 9 cases (1.3%), failed to Received 6/22/01; revised 10/19/01; accepted 10/29/01. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 Supported by Research Grant EDT-89 from the American Cancer Society, NIH Grant R01CA58427, and by grants from the Swedish Cancer Society. 2 To whom requests for reprints should be addressed, at Department of Epide- miology and Social Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Room 1301-A Belfer Building, Bronx, NY 10461. Phone (718) 430-3038; E-mail: pterry@aecom.yu.edu. 3 The abbreviations used are: EPA, eicosapentanoic acid; OR, odds ratio; CI, confidence interval. 143 Vol. 11, 143–145, January 2002 Cancer Epidemiology, Biomarkers & Prevention Research. on September 26, 2021. © 2002 American Association for Cancer cebp.aacrjournals.org Downloaded from