Cancer Causes & Control

, Volume 20, Issue 5, pp 699–711 | Cite as

Antioxidant vitamins and the risk of endometrial cancer: a dose–response meta-analysis

  • Elisa V. BanderaEmail author
  • Dina M. Gifkins
  • Dirk F. Moore
  • Marjorie L. McCullough
  • Lawrence H. Kushi
Original Paper


Antioxidant vitamins may reduce cancer risk by limiting oxidative DNA damage. To summarize and quantify the current epidemiologic evidence of an association between antioxidant vitamin intake and endometrial cancer, we conducted a systematic literature review and meta-analysis. One cohort and 12 case–control studies presenting relevant risk estimates were identified by conducting bibliographical searches through June 2008. Dose–response meta-analyses were conducted for beta-carotene, vitamin C, and vitamin E from food sources. Intake from supplements was not considered in the meta-analyses because of the few studies that reported relevant information. Based on case–control data, the random-effects summary odds ratios (OR) were, for beta-carotene: 0.88 (95% CI: 0.79–0.98) per 1,000 mcg/1,000 kcal (I2: 77.7%; p < 0.01); for vitamin C: 0.85 (95% CI: 0.73–0.98) per 50 mg/1,000 kcal (I2: 66.1%; p < 0.01); and, for vitamin E: 0.91 (95% CI: 0.84–0.99) per 5 mg/1,000 kcal (I2: 0.0%; p: 0.45). In contrast, the only prospective study identified provided little indication of an association. Although the current case–control data suggest an inverse relationship of endometrial cancer risk with dietary intakes of beta-carotene, vitamin C, and vitamin E from food sources, additional studies are needed, particularly cohort studies, to confirm an association.


Endometrial carcinoma Diet Vitamins Antioxidants Vitamin E Vitamin C Carotenoids Meta-analysis Systematic literature review 



World Cancer Research Fund International


American Institute for Cancer Research


Systematic Literature Review


Odds Ratio


Relative Risk


Confidence Interval


Food frequency questionnaire


Body mass index


Hormone replacement therapy



We would like to thank James Thomas for his valuable help with the data extraction access program. This work was funded in part by the WCRF and by the National Cancer Institute (NIH-K07 CA095666 to Dr. Bandera). However, interpretation of the evidence does not represent the views of WCRF, AICR, or the NCI.


  1. 1.
    American Cancer Society (2008) Cancer facts and figures 2008. American Cancer Society, Atlanta, GA.
  2. 2.
    Khan N, Afaq F, Mukhtar H (2008) Cancer chemoprevention through dietary antioxidants: progress and promise. Antioxid Redox Signal 10:475–510. doi: 10.1089/ars.2007.1740 PubMedCrossRefGoogle Scholar
  3. 3.
    World Cancer Research Fund, American Institute for Cancer Research (2007) Food, nutrition and the prevention of cancer: a global perspective. American Cancer Institute for Cancer Research, Washington, DCGoogle Scholar
  4. 4.
    Bandera EV, Kushi LH, Moore DF, Gifkins DM, McCullough ML (2007) The association between food, nutrition, and physical activity and the risk of endometrial cancer and underlying mechanisms. In: Second report on food, nutrition, physical activity and the prevention of cancer: World Cancer Research Fund International, American Institute for Cancer Research, Washington, DCGoogle Scholar
  5. 5.
    World Cancer Research Fund, American Institute for Cancer Research (1997) Food, nutrition and the prevention of cancer: a global perspective. American Cancer Institute for Cancer Research, Washington, DCGoogle Scholar
  6. 6.
    Bandera EV, Kushi LH, Moore DF, Gifkins DM, McCullough ML (2007) Fruits and vegetables and endometrial cancer risk: a systematic literature review and meta-analysis. Nutr Cancer 58:6–21PubMedGoogle Scholar
  7. 7.
    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 PubMedCrossRefGoogle Scholar
  8. 8.
    Bandera EV, Kushi LH, Moore DF, Gifkins DM, McCullough ML (2007) Dietary lipids and endometrial cancer: the current epidemiologic evidence. Cancer Causes Control 18:687–703. doi: 10.1007/s10552-007-9021-9 PubMedCrossRefGoogle Scholar
  9. 9.
    Bandera EV, Kushi LH, Moore DF, Gifkins DM, McCullough ML (2007) Association between dietary fiber and endometrial cancer: a dose–response meta-analysis. Am J Clin Nutr 86:1730–1737PubMedGoogle Scholar
  10. 10.
    Lee IM, Cook NR, Manson JE, Buring JE, Hennekens CH (1999) Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Women’s Health Study. J Natl Cancer Inst 91:2102–2106. doi: 10.1093/jnci/91.24.2102 PubMedCrossRefGoogle Scholar
  11. 11.
    Jain MG, Rohan TE, Howe GR, Miller AB (2000) A cohort study of nutritional factors and endometrial cancer. Eur J Epidemiol 16:899–905. doi: 10.1023/A:1011012621990 PubMedCrossRefGoogle Scholar
  12. 12.
    Knekt P, Aromaa A, Maatela J et al (1990) Serum vitamin A and subsequent risk of cancer: cancer incidence follow-up of the Finnish Mobile Clinic Health Examination Survey. Am J Epidemiol 132:857–870PubMedGoogle Scholar
  13. 13.
    Goodman MT, Hankin JH, Wilkens LR et al (1997) Diet, body size, physical activity, and the risk of endometrial cancer. Cancer Res 57:5077–5085PubMedGoogle Scholar
  14. 14.
    Goodman MT, Wilkens LR, Hankin JH, Lyu LC, Wu AH, Kolonel LN (1997) Association of soy and fiber consumption with the risk of endometrial cancer. Am J Epidemiol 146:294–306PubMedGoogle Scholar
  15. 15.
    Shu XO, Zheng W, Potischman N et al (1993) A population-based case–control study of dietary factors and endometrial cancer in Shanghai, People’s Republic of China. Am J Epidemiol 137:155–165PubMedGoogle Scholar
  16. 16.
    Potischman N, Swanson CA, Brinton LA et al (1993) Dietary associations in a case–control study of endometrial cancer. Cancer Causes Control 4:239–250PubMedGoogle Scholar
  17. 17.
    Jain MG, Howe GR, Rohan TE (2000) Nutritional factors and endometrial cancer in Ontario, Canada. Cancer Control 7:288–296PubMedGoogle Scholar
  18. 18.
    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. doi: 10.1023/A:1026551309873 PubMedCrossRefGoogle Scholar
  19. 19.
    Terry P, Vainio H, Wolk A, Weiderpass E (2002) Dietary factors in relation to endometrial cancer: a nationwide case–control study in Sweden. Nutr Cancer 42:25–32. doi: 10.1207/S15327914NC421_4 PubMedCrossRefGoogle Scholar
  20. 20.
    Tzonou A, Lipworth L, Kalandidi A et al (1996) Dietary factors and the risk of endometrial cancer: a case–control study in Greece. Br J Cancer 73:1284–1290PubMedGoogle Scholar
  21. 21.
    Xu WH, Dai Q, Xiang YB et al (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. doi: 10.1002/ijc.22456 PubMedCrossRefGoogle Scholar
  22. 22.
    La Vecchia C, Decarli A, Fasoli M, Gentile A (1986) Nutrition and diet in the etiology of endometrial cancer. Cancer 57:1248–1253. doi:10.1002/1097-0142(19860315)57:6<1248::AID-CNCR2820570631>3.0.CO;2-VPubMedCrossRefGoogle Scholar
  23. 23.
    Negri E, La Vecchia C, Franceschi S, Levi F, Parazzini F (1996) Intake of selected micronutrients and the risk of endometrial carcinoma. Cancer 77:917–923. doi:10.1002/(SICI)1097-0142(19960301)77:5<917::AID-CNCR17>3.0.CO;2-6PubMedCrossRefGoogle Scholar
  24. 24.
    Levi F, Franceschi S, Negri E, La Vecchia C (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;2-0PubMedCrossRefGoogle Scholar
  25. 25.
    Barbone F, Austin H, Partridge EE (1993) Diet and endometrial cancer: a case–control study. Am J Epidemiol 137:393–403PubMedGoogle Scholar
  26. 26.
    Salazar-Martinez E, Lazcano-Ponce E, Sanchez-Zamorano LM, Gonzalez-Lira G, Escudero-De los Rios P, Hernandez-Avila M (2005) Dietary factors and endometrial cancer risk. Results of a case–control study in Mexico. Int J Gynecol Cancer 15:938–945. doi: 10.1111/j.1525-1438.2005.00253.x PubMedCrossRefGoogle Scholar
  27. 27.
    Rothman KJ (1986) Modern epidemiology, 1st edn. Little, Brown, Boston, pp 174–175Google Scholar
  28. 28.
    Chene G, Thompson SG (1996) Methods for summarizing the risk associations of quantitative variables in epidemiologic studies in a consistent form. Am J Epidemiol 144:610–621PubMedGoogle Scholar
  29. 29.
    Greenland S, Longnecker MP (1992) Methods for trend estimation from summarized dose–response data, with applications to meta-analysis. Am J Epidemiol 135:1301–1309PubMedGoogle Scholar
  30. 30.
    Burke TW, Eifel PJ, Muggia FM (2001) Cancer of the uterine body. In: DeVita VT, Hellman S, Rosenberg SA (eds) Cancer: principles & practice of oncology, 6th edn. Lippincott, PhiladelphiaGoogle Scholar
  31. 31.
    Bendich A (2004) From 1989 to 2001: what have we learned about the “biological actions of beta-carotene”? J Nutr 134:225S–230SPubMedGoogle Scholar
  32. 32.
    Krinsky NI (1991) Effects of carotenoids in cellular and animal systems. Am J Clin Nutr 53:238S–246SPubMedGoogle Scholar
  33. 33.
    Chew BP, Park JS (2004) Carotenoid action on the immune response. J Nutr 134:257S–261SPubMedGoogle Scholar
  34. 34.
    Omenn GS, Goodman GE, Thornquist MD et al (1996) Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 334:1150–1155. doi: 10.1056/NEJM199605023341802 PubMedCrossRefGoogle Scholar
  35. 35.
    The Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 330:1029–1035. doi: 10.1056/NEJM199404143301501 CrossRefGoogle Scholar
  36. 36.
    Lee KW, Lee HJ, Surh YJ, Lee CY (2003) Vitamin C and cancer chemoprevention: reappraisal. Am J Clin Nutr 78:1074–1078PubMedGoogle Scholar
  37. 37.
    Duarte TL, Lunec J (2005) Review: when is an antioxidant not an antioxidant? A review of novel actions and reactions of vitamin C. Free Radic Res 39:671–686. doi: 10.1080/10715760500104025 PubMedCrossRefGoogle Scholar
  38. 38.
    Seifried HE, McDonald SS, Anderson DE, Greenwald P, Milner JA (2003) The antioxidant conundrum in cancer. Cancer Res 63:4295–4298PubMedGoogle Scholar
  39. 39.
    Lunec J, Halligan E, Mistry N, Karakoula K (2004) Effect of vitamin E on gene expression changes in diet-related carcinogenesis. Ann N Y Acad Sci 1031:169–183. doi: 10.1196/annals.1331.016 PubMedCrossRefGoogle Scholar
  40. 40.
    Beharka A, Redican S, Leka L, Meydani SN (1997) Vitamin E status and immune function. Methods Enzymol 282:247–263. doi: 10.1016/S0076-6879(97)82112-X PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Elisa V. Bandera
    • 1
    • 2
    Email author
  • Dina M. Gifkins
    • 1
    • 2
  • Dirk F. Moore
    • 2
  • Marjorie L. McCullough
    • 3
  • Lawrence H. Kushi
    • 4
  1. 1.The Cancer Institute of New Jersey, Robert Wood Johnson Medical SchoolNew BrunswickUSA
  2. 2.School of Public HealthUniversity of Medicine and Dentistry of New JerseyPiscatawayUSA
  3. 3.Epidemiology and Surveillance Research, American Cancer SocietyAtlantaUSA
  4. 4.Division of ResearchKaiser PermanenteOaklandUSA

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