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Omega-3 and omega-6 fatty acid intakes and endometrial cancer risk in a population-based case–control study

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Abstract

Purpose

Animal and laboratory studies suggest that long-chain omega-3 (n-3) fatty acids, a type of polyunsaturated fat found in fatty fish, may protect against carcinogenesis, but human studies on dietary intake of polyunsaturated fats and fish with endometrial cancer risk show mixed results.

Methods

We evaluated the associations between endometrial cancer risk and intake of fatty acids and fish in a population-based sample of 556 incident cancer cases and 533 age-matched controls using multivariate unconditional logistic regression methods.

Results

Although total n-3 fatty acid intake was not associated with endometrial cancer risk, higher intakes of eicosapentaenoic (EPA 20:5) and docosahexaenoic (DHA 22:6) fatty acids were significantly associated with lower risks (OR = 0.57, 95 % CI: 0.39–0.84; OR = 0.64, 95 % CI: 0.44–0.94; respectively) comparing extreme quartiles. The ratio of n-3:n-6 fatty acids was inversely associated with risk only on a continuous scale (OR = 0.84, 95 % CI: 0.71–0.99), while total fish intake was not associated with risk. Fish oil supplement use was significantly associated with reduced risk of endometrial cancer: OR = 0.63 (95 % CI: 0.45–0.88).

Conclusions

Our results suggest that dietary intake of the long-chain polyunsaturated fatty acids EPA and DHA in foods and supplements may have protective associations against the development of endometrial cancer.

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References

  1. American Cancer Society (2012) Cancer facts & figures 2012. American Cancer Society, Atlanta

    Google Scholar 

  2. Akhmedkhanov A, Zeleniuch-Jacquotte A, Toniolo P (2001) Role of exogenous and endogenous hormones in endometrial cancer. Ann NY Acad Sci 943:296–315. doi:10.1111/j.1749-6632.2001.tb03811.x

    Article  CAS  Google Scholar 

  3. Purdie DM, Green AC (2001) Epidemiology of endometrial cancer. Best Pract Res Clin Obstet Gynaecol 15:341–354. doi:10.1053/beog.2000.0180

    Article  CAS  Google Scholar 

  4. Fader AN, Arriba LN, Frasure HE, von Gruenigen VE (2009) Endometrial cancer and obesity: epidemiology, biomarkers, prevention and survivorship. Gynecol Oncol 114:121–127

    Article  Google Scholar 

  5. Arem H, Irwin ML, Zhou Y, Lu L, Risch H, Yu H (2010) Physical activity and endometrial cancer in a population-based case-control study. Cancer Causes Control 22:219–226. doi:10.1007/s10552-010-9689-0

    Article  Google Scholar 

  6. Terry P, Baron JA, Weiderpass E, Yuen J, Lichtenstein P, Nyren O (1999) Lifestyle and endometrial cancer risk: a cohort study from the Swedish twin registry. Int J Cancer 82:38–42

    Article  CAS  Google Scholar 

  7. Karmali RA, Marsh J, Fuchs C (1984) Effect of omega-3 fatty acids on growth of a rat mammary tumor. J Natl Cancer Inst 73:457–461

    CAS  Google Scholar 

  8. Lindner MA (1991) A fish oil diet inhibits colon cancer in mice. Nutr Cancer 15:1–11. doi:10.1080/01635589109514105

    Article  CAS  Google Scholar 

  9. Tsai WS, Nagawa H, Kaizaki S, Tsuruo T, Muto T (1998) Inhibitory effects of n-3 polyunsaturated fatty acids on sigmoid colon cancer transformants. J Gastroenterol 33:206–212

    Article  CAS  Google Scholar 

  10. Boudreau MD, Sohn KH, Rhee SH, Lee SW, Hunt JD, Hwang DH (2001) Suppression of tumor cell growth both in nude mice and in culture by n-3 polyunsaturated fatty acids: mediation through cyclooxygenase-independent pathways. Cancer Res 61:1386

    CAS  Google Scholar 

  11. Rose DP, Connolly JM, Meschter CL (1991) Effect of dietary fat on human breast cancer growth and lung metastasis in nude mice. J Natl Cancer Inst 83:1491–1495

    Article  CAS  Google Scholar 

  12. Larsson SC, Kumlin M, Ingelman-Sundberg M, Wolk A (2004) Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms. Am J Clin Nutr 79:935–945

    CAS  Google Scholar 

  13. Sasaki T, Kobayashi Y, Shimizu J, Wada M, In’nami S, Kanke Y, Takita T (1998) Effects of dietary n-3-to-n-6 polyunsaturated fatty acid ratio on mammary carcinogenesis in rats. Nutr Cancer 30:137–143. doi:10.1080/01635589809514653

    Article  CAS  Google Scholar 

  14. Zheng W, Kushi LH, Potter JD, Sellers TA, Doyle TJ, Bostick RM, Folsom AR (1995) Dietary intake of energy and animal foods and endometrial cancer incidence. Am J Epidemiol 142:388

    CAS  Google Scholar 

  15. Cui X, Rosner B, Willett WC, Hankinson SE (2011) Dietary fat, fiber, and carbohydrate intake in relation to risk of endometrial cancer. Cancer Epidemiol Biomarkers Prev. doi:10.1158/1055-9965.EPI-10-1089

    Google Scholar 

  16. McCann SE, Freudenheim JL, Marshall JR, Brasure JR, Swanson MK, Graham S (2000) Diet in the epidemiology of endometrial cancer in western New York (United States). Cancer Causes Control 11:965–974

    Article  CAS  Google Scholar 

  17. Fernandez E, Chatenoud L, La Vecchia C, Negri E, Franceschi S (1999) Fish consumption and cancer risk. Am J Clin Nutr 70:85–90

    CAS  Google Scholar 

  18. Hirose K, Tajima K, Hamajima N, Takezaki T, Inoue M, Kuroishi T, Kuzuya K, Nakamura S, Tokudome S (1996) Subsite (cervix/endometrium)-specific Risk and Protective Factors in Uterus Cancer. Cancer Sci 87:1001–1009

    Article  CAS  Google Scholar 

  19. Goodman MT, Hankin JH, Wilkens LR, Lyu LC, McDuffie K, Liu LQ, Kolonel LN (1997) Diet, body size, physical activity, and the risk of endometrial cancer. Cancer Res 57:5077–5085

    CAS  Google Scholar 

  20. Levi F, La Vecchia C, Franceschi S, Negri E (1993) Dietary factors and the risk of endometrial cancer. Cancer 71:3575–3581. doi:10.1002/1097-0142(19930601)71:11<3575:aid-cncr2820711119>3.0.co;2-0

    Article  CAS  Google Scholar 

  21. Bravi F, Scotti L, Bosetti C, Zucchetto A, Talamini R, Montella M, Greggi S, Pelucchi C, Negri E, Franceschi S (2009) Food groups and endometrial cancer risk: a case-control study from Italy. Am J Obstet Gynecol 200:293. e291–293. e297

    Google Scholar 

  22. Jain MG, Howe GR, Rohan TE (2000) Nutritional factors and endometrial cancer in Ontario, Canada. Cancer Control 7:288–296

    CAS  Google Scholar 

  23. Xu WH, Dai Q, Xiang YB, Zhao GM, Zheng W, Gao YT, Ruan ZX, Cheng JR, Shu XO (2006) Animal food intake and cooking methods in relation to endometrial cancer risk in Shanghai. Br J Cancer 95:1586–1592

    Article  CAS  Google Scholar 

  24. Shu XO, Zheng W, Potischman N, Brinton LA, Hatch MC, Gao Y-T, Fraumeni JF (1993) A population-based case-control study of dietary factors and endometrial cancer in Shanghai, People’s Republic of China. Am J Epidemiol 137:155–165

    CAS  Google Scholar 

  25. Terry P, Wolk A, Vainio H, Weiderpass E (2002) Fatty fish consumption lowers the risk of endometrial cancer: a nationwide case-control study in Sweden. Cancer Epidemiol Biomarkers Prev 11:143–145

    Google Scholar 

  26. Tzonou A, Lipworth L, Kalandidi A, Trichopoulou A, Gamatsi I, Hsieh CC, Notara V, Trichopoulos D (1996) Dietary factors and the risk of endometrial cancer: a case-control study in Greece. Br J Cancer 73:1284

    Article  CAS  Google Scholar 

  27. Xu WH, Dai Q, Xiang YB, Zhao GM, Ruan ZX, Cheng JR, Zheng W, Shu XO (2007) Nutritional factors in relation to endometrial cancer: a report from a population based case control study in Shanghai, China. Int J Cancer 120:1776–1781

    Article  CAS  Google Scholar 

  28. Patterson RE, Kristal AR, Tinker LF, Carter RA, Bolton MP, Agurs-Collins T (1999) Measurement characteristics of the Women’s Health Initiative food frequency questionnaire. Ann Epidemiol 9:178–187

    Article  CAS  Google Scholar 

  29. Kushi LH, Fee RM, Sellers TA, Zheng W, Folsom AR (1996) Intake of vitamins A, C, and E and postmenopausal breast cancer: the Iowa Women’s Health Study. Am J Epidemiol 144:165–174

    Article  CAS  Google Scholar 

  30. Horn-Ross PL, John EM, Lee M, Stewart SL, Koo J, Sakoda LC, Shiau AC, Goldstein J, Davis P, Perez-Stable EJ (2001) Phytoestrogen consumption and breast cancer risk in a multiethnic population. Am J Epidemiol 154:434–441. doi:10.1093/aje/154.5.434

    Article  CAS  Google Scholar 

  31. Willett W (1998) Nutritional epidemiology. Oxford University Press, New York

    Book  Google Scholar 

  32. Jain MG, Rohan TE, Howe GR, Miller AB (2000) A cohort study of nutritional factors and endometrial cancer. Eur J Epidemiol 16:899–905

    Article  CAS  Google Scholar 

  33. Littman A, Beresford S, White E (2001) The association of dietary fat and plant foods with endometrial cancer (United States). Cancer Causes Control 12:691–702. doi:10.1023/a:1011292003586

    Article  CAS  Google Scholar 

  34. Meyer BJ, Mann NJ, Lewis JL, Milligan GC, Sinclair AJ, Howe PRC (2003) Dietary intakes and food sources of omega-6 and omega-3 polyunsaturated fatty acids. Lipids 38:391–398

    Article  CAS  Google Scholar 

  35. Kris-Etherton PM, Harris WS, Appel LJ (2002) Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 106:2747–2757

    Article  Google Scholar 

  36. Bandera EV, Kushi LH, Moore DF, Gifkins DM, McCullough ML (2007) Consumption of animal foods and endometrial cancer risk: a systematic literature review and meta-analysis. Cancer Causes Control 18:967–988. doi:10.1007/s10552-007-9038-0

    Article  Google Scholar 

  37. Rose DP, Connolly JM (1999) Omega-3 fatty acids as cancer chemopreventive agents. Pharmacol Ther 83:217–244

    Article  CAS  Google Scholar 

  38. Judé S, Roger S, Martel E, Besson P, Richard S, Bougnoux P, Champeroux P, Le Guennec JY (2006) Dietary long-chain omega-3 fatty acids of marine origin: a comparison of their protective effects on coronary heart disease and breast cancers. Prog Biophys Mol Biol 90:299–325

    Article  Google Scholar 

  39. Calder PC (2006) n-3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83:S1505–1519S

    Google Scholar 

  40. Takahashi M, Przetakiewicz M, Ong A, Borek C, Lowenstein JM (1992) Effect of omega 3 and omega 6 fatty acids on transformation of cultured cells by irradiation and transfection. Cancer Res 52:154–162

    CAS  Google Scholar 

  41. Needleman P, Raz A, Minkes MS, Ferrendelli JA, Sprecher H (1979) Triene prostaglandins: prostacyclin and thromboxane biosynthesis and unique biological properties. Proc Natl Acad Sci USA 76:944

    Article  CAS  Google Scholar 

  42. Jump DB (2002) Dietary polyunsaturated fatty acids and regulation of gene transcription. Curr Opin Lipidol 13:155

    Article  CAS  Google Scholar 

  43. Yang P, Chan D, Felix E, Cartwright C, Menter DG, Madden T, Klein RD, Fischer SM, Newman RA (2004) Formation and antiproliferative effect of prostaglandin E3 from eicosapentaenoic acid in human lung cancer cells. J Lipid Res 45:1030–1039

    Article  CAS  Google Scholar 

  44. Calder P, Grimble R (2002) Polyunsaturated fatty acids, inflammation and immunity. Eur J Clin Nutr 56:S14

    Article  CAS  Google Scholar 

  45. Mori Y, Murakawa Y, Katoh S, Hata S, Yokoyama J, Tajima N, Ikeda Y, Nobukata H, Ishikawa T, Shibutani Y (1997) Influence of highly purified eicosapentaenoic acid ethyl ester on insulin resistance in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous non-insulin-dependent diabetes mellitus. Metabolism 46:1458–1464

    Article  CAS  Google Scholar 

  46. Pérez-Matute P, Pérez-Echarri N, Martinez JA, Marti A, Moreno-Aliaga MJ (2007) Eicosapentaenoic acid actions on adiposity and insulin resistance in control and high-fat-fed rats: role of apoptosis, adiponectin and tumour necrosis factor-alpha. Br J Nutr 97:389–398

    Article  Google Scholar 

  47. Popp-Snijders C, Schouten J, Heine R, Van der Meer J, Van der Veen E (1987) Dietary supplementation of omega-3 polyunsaturated fatty acids improves insulin sensitivity in non-insulin-dependent diabetes. Diabetes Res 4:141

    CAS  Google Scholar 

  48. Weaver KL, Ivester P, Chilton JA, Wilson MD, Pandey P, Chilton FH (2008) The content of favorable and unfavorable polyunsaturated fatty acids found in commonly eaten fish. J Am Diet Assoc 108:1178–1185. doi:10.1016/j.jada.2008.04.023

    Article  CAS  Google Scholar 

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Acknowledgments

HA was supported in part by NIH doctoral training grant T32 CA105666. MN was supported by P30 CA15704. The Connecticut Endometrial Cancer Study was supported by NIH research grant 5R01 CA098346 (to HY). The cooperation of 28 Connecticut hospitals, including Charlotte Hungerford Hospital, Bridgeport Hospital, Danbury Hospital, Hartford Hospital, Middlesex Hospital, New Britain General Hospital, Bradley Memorial Hospital, Yale/New Haven Hospital, St. Francis Hospital and Medical Center, St. Mary’s Hospital, Hospital of St. Raphael, St. Vincent’s Medical Center, Stamford Hospital, William W. Backus Hospital, Windham Hospital, Eastern Connecticut Health Network, Griffin Hospital, Bristol Hospital, Johnson Memorial Hospital, Day Kimball Hospital, Greenwich Hospital, Lawrence and Memorial Hospital, Milford Hospital, New Milford Hospital, Norwalk Hospital, MidState Medical Center, John Dempsey Hospital and Waterbury Hospital, in allowing patient access, is gratefully acknowledged. This study was approved by the State of Connecticut Department of Public Health Human Investigation Committee. Certain data used in this study were obtained from the Connecticut Tumor Registry in the Connecticut Department of Public Health. The authors assume full responsibility for analyses and interpretation of these data. The authors want especially to thank Rajni Mehta for her support in case identification through Rapid Case Ascertainment, Helen Sayward for her effort in conducting the study, Ellen Anderson, Donna Bowers, Renee Capasso, Kristin DeFrancesco, Anna Florczak, and Sherry Rowland for their assistance in recruiting and interviewing study participants, and Na Ni for her help in SAS programming.

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Authors and Affiliations

  1. Yale School of Public Health, 60 College Street, P.O. Box 208034, New Haven, CT, 06520, USA

    Hannah Arem & Lingeng Lu

  2. Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA

    Marian L. Neuhouser

  3. Yale Cancer Center, New Haven, CT, 06520, USA

    Melinda L. Irwin, Brenda Cartmel, Harvey Risch & Susan T. Mayne

  4. University of Hawaii Cancer Center, Honolulu, HI, USA

    Herbert Yu

  5. Yale School of Public Health, School of Medicine, 60 College Street, P.O. Box 208034, New Haven, CT, 06520, USA

    Melinda L. Irwin, Brenda Cartmel, Harvey Risch, Susan T. Mayne & Herbert Yu

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  1. Hannah Arem
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Correspondence to Hannah Arem.

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Arem, H., Neuhouser, M.L., Irwin, M.L. et al. Omega-3 and omega-6 fatty acid intakes and endometrial cancer risk in a population-based case–control study. Eur J Nutr 52, 1251–1260 (2013). https://doi.org/10.1007/s00394-012-0436-z

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  • DOI: https://doi.org/10.1007/s00394-012-0436-z

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