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Retinol, vitamins A, C, and E and breast cancer risk: a meta-analysis and meta-regression

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Abstract

Objective

To comprehensively summarize the associations between retinol, vitamins A, C, and E and breast cancer, and quantitatively estimate their dose–response relationships.

Methods

We searched PubMed, Embase, and Cochrane databases (from January 1982 to 15 March 2011) and the references of the relevant articles in English with sufficient information to estimate relative risk or odds ratio and the 95% confidence intervals, and comparable categories of vitamins. Two reviewers independently extracted data using a standardized form, with any discrepancy adjudicated by the third reviewer.

Results

Overall, 51 studies met the inclusion criteria. Comparing the highest with the lowest intake, total vitamin A intake reduced the breast cancer risk by 17% (pooled OR = 0.83, 95% CI: 0.78–0.88). Further subgroup analysis based on study design did not change the significant reduction. Although the dietary vitamin A, dietary vitamin E, and total vitamin E intake all reduced breast cancer risk significantly when data from all studies were pooled, the results became nonsignificant when data from cohort studies were pooled. The significant association between total retinol intake and breast cancer in all studies became nonsignificant in case–control studies but remain significant in cohort studies. No significant dose–response relationship was observed in the higher intake of these vitamins with reduced breast cancer risk.

Conclusions

Our results indicate that both the total intake of vitamin A and retinol could reduce breast cancer risk. However, associations between other vitamins and breast cancer seem to be limited.

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References

  1. Buell P (1973) Changing incidence of breast cancer in Japanese-American women. J Natl Cancer Inst 51(5):1479–1483

    PubMed  CAS  Google Scholar 

  2. Thomas DB, Karagas MR (1987) Cancer in first and second generation Americans. Cancer Res 47(21):5771–5776

    PubMed  CAS  Google Scholar 

  3. Armstrong B, Doll R (1975) Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices. Int J Cancer 15(4):617–631

    Article  PubMed  CAS  Google Scholar 

  4. Kelsey JL, Horn-Ross PL (1993) Breast cancer: magnitude of the problem and descriptive epidemiology. Epidemiol Rev 15(1):7–16

    PubMed  CAS  Google Scholar 

  5. Altucci L, Gronemeyer H (2001) The promise of retinoids to fight against cancer. Nat Rev Cancer 1(3):181–193

    Article  PubMed  CAS  Google Scholar 

  6. Aggarwal BB, Sundaram C, Prasad S, Kannappan R (2010) Tocotrienols, the vitamin E of the 21st century: its potential against cancer and other chronic diseases. Biochem Pharmacol 80(11):1613–1631

    Article  PubMed  CAS  Google Scholar 

  7. Ullah MF, Khan HY, Zubair H, Shamim U, Hadi SM (2011) The antioxidant ascorbic acid mobilizes nuclear copper leading to a prooxidant breakage of cellular DNA: implications for chemotherapeutic action against cancer. Cancer Chemother Pharmacol 67(1):103–110

    Article  PubMed  CAS  Google Scholar 

  8. Zhang S, Hunter DJ, Forman MR, Rosner BA, Speizer FE, Colditz GA, Manson JE, Hankinson SE, Willett WC (1999) Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. J Natl Cancer Inst 91(6):547–556

    Article  PubMed  CAS  Google Scholar 

  9. Cho E, Spiegelman D, Hunter DJ, Chen WY, Zhang SM, Colditz GA, Willett WC (2003) Premenopausal intakes of vitamins A, C, and E, folate, and carotenoids, and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 12(8):713–720

    PubMed  CAS  Google Scholar 

  10. Bohlke K, Spiegelman D, Trichopoulou A, Katsouyanni K, Trichopoulos D (1999) Vitamins A, C and E and the risk of breast cancer: results from a case-control study in Greece. Br J Cancer 79(1):23–29

    Article  PubMed  CAS  Google Scholar 

  11. Ronco A, De Stefani E, Boffetta P, Deneo-Pellegrini H, Mendilaharsu M, Leborgne F (1999) Vegetables, fruits, and related nutrients and risk of breast cancer: a case-control study in Uruguay. Nutr Cancer 35(2):111–119

    Article  PubMed  CAS  Google Scholar 

  12. Adzersen KH, Jess P, Freivogel KW, Gerhard I, Bastert G (2003) Raw and cooked vegetables, fruits, selected micronutrients, and breast cancer risk: a case-control study in Germany. Nutr Cancer 46(2):131–137

    Article  PubMed  CAS  Google Scholar 

  13. Nissen SB, Tjonneland A, Stripp C, Olsen A, Christensen J, Overvad K, Dragsted LO, Thomsen B (2003) Intake of vitamins A, C, and E from diet and supplements and breast cancer in postmenopausal women. Cancer Causes Control 14(8):695–704

    Article  PubMed  Google Scholar 

  14. Levi F, Pasche C, Lucchini F, La Vecchia C (2001) Dietary intake of selected micronutrients and breast-cancer risk. Int J Cancer 91(2):260–263

    Article  PubMed  CAS  Google Scholar 

  15. Michels KB, Holmberg L, Bergkvist L, Ljung H, Bruce A, Wolk A (2001) Dietary antioxidant vitamins, retinol, and breast cancer incidence in a cohort of Swedish women. Int J Cancer 91(4):563–567

    Article  PubMed  CAS  Google Scholar 

  16. Do MH, Lee SS, Jung PJ, Lee MH (2003) Intake of dietary fat and vitamin in relation to breast cancer risk in Korean women: a case-control study. J Korean Med Sci 18(4):534–540

    PubMed  CAS  Google Scholar 

  17. Moorman PG, Ricciuti MF, Millikan RC, Newman B (2001) Vitamin supplement use and breast cancer in a North Carolina population. Public Health Nutr 4(3):821–827

    Article  PubMed  CAS  Google Scholar 

  18. Dorjgochoo T, Shrubsole MJ, Shu XO, Lu W, Ruan Z, Zheng Y, Cai H, Dai Q, Gu K, Gao YT et al (2008) Vitamin supplement use and risk for breast cancer: the Shanghai Breast Cancer Study. Breast Cancer Res Treat 111(2):269–278

    Article  PubMed  CAS  Google Scholar 

  19. Wang C, Baumgartner RN, Yang D, Slattery ML, Murtaugh MA, Byers T, Hines LM, Giuliano AR, Baumgartner KB (2009) No evidence of association between breast cancer risk and dietary carotenoids, retinols, vitamin C and tocopherols in Southwestern Hispanic and non-Hispanic White women. Breast Cancer Res Treat 114(1):137–145

    Article  PubMed  CAS  Google Scholar 

  20. Challier B, Perarnau JM, Viel JF (1998) Garlic, onion and cereal fibre as protective factors for breast cancer: a French case-control study. Eur J Epidemiol 14(8):737–747

    Article  PubMed  CAS  Google Scholar 

  21. Cui Y, Shikany JM, Liu S, Shagufta Y, Rohan TE (2008) Selected antioxidants and risk of hormone receptor-defined invasive breast cancers among postmenopausal women in the Women’s Health Initiative Observational Study. Am J Clin Nutr 87(4):1009–1018

    PubMed  CAS  Google Scholar 

  22. Malin AS, Qi D, Shu XO, Gao YT, Friedmann JM, Jin F, Zheng W (2003) Intake of fruits, vegetables and selected micronutrients in relation to the risk of breast cancer. Int J Cancer 105(3):413–418

    Article  PubMed  CAS  Google Scholar 

  23. Gaudet MM, Britton JA, Kabat GC, Steck-Scott S, Eng SM, Teitelbaum SL, Terry MB, Neugut AI, Gammon MD (2004) Fruits, vegetables, and micronutrients in relation to breast cancer modified by menopause and hormone receptor status. Cancer Epidemiol Biomarkers Prev 13(9):1485–1494

    PubMed  CAS  Google Scholar 

  24. Mannisto S, Pietinen P, Virtanen M, Kataja V, Uusitupa M (1999) Diet and the risk of breast cancer in a case-control study: does the threat of disease have an influence on recall bias? J Clin Epidemiol 52(5):429–439

    Article  PubMed  CAS  Google Scholar 

  25. Mignone LI, Giovannucci E, Newcomb PA, Titus-Ernstoff L, Trentham-Dietz A, Hampton JM, Willett WC, Egan KM (2009) Dietary carotenoids and the risk of invasive breast cancer. Int J Cancer 124(12):2929–2937

    Article  PubMed  CAS  Google Scholar 

  26. Sharhar S, Normah H, Fatimah A, Fadilah RN, Rohi GA, Amin I, Cham BG, Rizal RM, Fairulnizal MN (2008) Antioxidant intake and status, and oxidative stress in relation to breast cancer risk: a case-control study. Asian Pac J Cancer Prev 9(2):343–349

    PubMed  Google Scholar 

  27. Nagel G, Linseisen J, van Gils CH, Peeters PH, Boutron-Ruault MC, Clavel-Chapelon F, Romieu I, Tjonneland A, Olsen A, Roswall N et al (2010) Dietary beta-carotene, vitamin C and E intake and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Breast Cancer Res Treat 119(3):753–765

    Article  PubMed  CAS  Google Scholar 

  28. Zhang CX, Ho SC, Chen YM, Fu JH, Cheng SZ, Lin FY (2009) Greater vegetable and fruit intake is associated with a lower risk of breast cancer among Chinese women. Int J Cancer 125(1):181–188

    Article  PubMed  CAS  Google Scholar 

  29. Bonilla-Fernandez P, Lopez-Cervantes M, Torres-Sanchez LE, Tortolero-Luna G, Lopez-Carrillo L (2003) Nutritional factors and breast cancer in Mexico. Nutr Cancer 45(2):148–155

    Article  PubMed  CAS  Google Scholar 

  30. Potischman N, Swanson CA, Coates RJ, Gammon MD, Brogan DR, Curtin J, Brinton LA (1999) Intake of food groups and associated micronutrients in relation to risk of early-stage breast cancer. Int J Cancer 82(3):315–321

    Article  PubMed  CAS  Google Scholar 

  31. Lee MM, Chang IY, Horng CF, Chang JS, Cheng SH, Huang A (2005) Breast cancer and dietary factors in Taiwanese women. Cancer Causes Control 16(8):929–937

    Article  PubMed  Google Scholar 

  32. Longnecker MP, Newcomb PA, Mittendorf R, Greenberg ER, Willett WC (1997) Intake of carrots, spinach, and supplements containing vitamin A in relation to risk of breast cancer. Cancer Epidemiol Biomarkers Prev 6(11):887–892

    PubMed  CAS  Google Scholar 

  33. Howe GR, Hirohata T, Hislop TG, Iscovich JM, Yuan JM, Katsouyanni K, Lubin F, Marubini E, Modan B, Rohan T et al (1990) Dietary factors and risk of breast cancer: combined analysis of 12 case-control studies. J Natl Cancer Inst 82(7):561–569

    Article  PubMed  CAS  Google Scholar 

  34. Gandini S, Merzenich H, Robertson C, Boyle P (2000) Meta-analysis of studies on breast cancer risk and diet: the role of fruit and vegetable consumption and the intake of associated micronutrients. Eur J Cancer 36(5):636–646

    Article  PubMed  CAS  Google Scholar 

  35. Alkhenizan A, Hafez K (2007) The role of vitamin E in the prevention of cancer: a meta-analysis of randomized controlled trials. Ann Saudi Med 27(6):409–414

    Article  PubMed  Google Scholar 

  36. Berlin JA, Longnecker MP, Greenland S (1993) Meta-analysis of epidemiologic dose-response data. Epidemiology 4(3):218–228

    Article  PubMed  CAS  Google Scholar 

  37. 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(6):610–621

    PubMed  CAS  Google Scholar 

  38. Trock BJ, Hilakivi-Clarke L, Clarke R (2006) Meta-analysis of soy intake and breast cancer risk. J Natl Cancer Inst 98(7):459–471

    Article  PubMed  CAS  Google Scholar 

  39. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560

    Article  PubMed  Google Scholar 

  40. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    PubMed  CAS  Google Scholar 

  41. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101

    Article  PubMed  CAS  Google Scholar 

  42. Negri E, La Vecchia C, Franceschi S, D’Avanzo B, Talamini R, Parpinel M, Ferraroni M, Filiberti R, Montella M, Falcini F et al (1996) Intake of selected micronutrients and the risk of breast cancer. Int J Cancer 65(2):140–144

    Article  PubMed  CAS  Google Scholar 

  43. Graham S, Marshall J, Mettlin C, Rzepka T, Nemoto T, Byers T (1982) Diet in the epidemiology of breast cancer. Am J Epidemiol 116(1):68–75

    PubMed  CAS  Google Scholar 

  44. Zaridze D, Lifanova Y, Maximovitch D, Day NE, Duffy SW (1991) Diet, alcohol consumption and reproductive factors in a case-control study of breast cancer in Moscow. Int J Cancer 48(4):493–501

    Article  PubMed  CAS  Google Scholar 

  45. Katsouyanni K, Willett W, Trichopoulos D, Boyle P, Trichopoulou A, Vasilaros S, Papadiamantis J, MacMahon B (1988) Risk of breast cancer among Greek women in relation to nutrient intake. Cancer 61(1):181–185

    Article  PubMed  CAS  Google Scholar 

  46. Lee HP, Gourley L, Duffy SW, Esteve J, Lee J, Day NE (1991) Dietary effects on breast-cancer risk in Singapore. Lancet 337(8751):1197–1200

    Article  PubMed  CAS  Google Scholar 

  47. London SJ, Stein EA, Henderson IC, Stampfer MJ, Wood WC, Remine S, Dmochowski JR, Robert NJ, Willett WC (1992) Carotenoids, retinol, and vitamin E and risk of proliferative benign breast disease and breast cancer. Cancer Causes Control 3(6):503–512

    Article  PubMed  CAS  Google Scholar 

  48. Qi XY, Zhang AY, Wu GL, Pang WZ (1994) The association between breast cancer and diet and other factors. Asia Pac J Public Health 7(2):98–104

    Article  PubMed  CAS  Google Scholar 

  49. Levi F, La Vecchia C, Gulie C, Negri E (1993) Dietary factors and breast cancer risk in Vaud, Switzerland. Nutr Cancer 19(3):327–335

    Article  PubMed  CAS  Google Scholar 

  50. Potischman N, McCulloch CE, Byers T, Nemoto T, Stubbe N, Milch R, Parker R, Rasmussen KM, Root M, Graham S (1990) Breast cancer and dietary and plasma concentrations of carotenoids and vitamin A. Am J Clin Nutr 52(5):909–915

    PubMed  CAS  Google Scholar 

  51. Landa MC, Frago N, Tres A (1994) Diet and the risk of breast cancer in Spain. Eur J Cancer Prev 3(4):313–320

    Article  PubMed  CAS  Google Scholar 

  52. Richardson S, Gerber M, Cenee S (1991) The role of fat, animal protein and some vitamin consumption in breast cancer: a case control study in southern France. Int J Cancer 48(1):1–9

    PubMed  CAS  Google Scholar 

  53. Marubini E, Decarli A, Costa A, Mazzoleni C, Andreoli C, Barbieri A, Capitelli E, Carlucci M, Cavallo F, Monferroni N et al (1988) The relationship of dietary intake and serum levels of retinol and beta-carotene with breast cancer. Results of a case-control study. Cancer 61(1):173–180

    Article  PubMed  CAS  Google Scholar 

  54. La Vecchia C, Decarli A, Franceschi S, Gentile A, Negri E, Parazzini F (1987) Dietary factors and the risk of breast cancer. Nutr Cancer 10(4):205–214

    Article  PubMed  CAS  Google Scholar 

  55. Freudenheim JL, Marshall JR, Vena JE, Laughlin R, Brasure JR, Swanson MK, Nemoto T, Graham S (1996) Premenopausal breast cancer risk and intake of vegetables, fruits, and related nutrients. J Natl Cancer Inst 88(6):340–348

    Article  PubMed  CAS  Google Scholar 

  56. Graham S, Hellmann R, Marshall J, Freudenheim J, Vena J, Swanson M, Zielezny M, Nemoto T, Stubbe N, Raimondo T (1991) Nutritional epidemiology of postmenopausal breast cancer in western New York. Am J Epidemiol 134(6):552–566

    PubMed  CAS  Google Scholar 

  57. Iscovich JM, Iscovich RB, Howe G, Shiboski S, Kaldor JM (1989) A case-control study of diet and breast cancer in Argentina. Int J Cancer 44(5):770–776

    Article  PubMed  CAS  Google Scholar 

  58. Rohan TE, McMichael AJ, Baghurst PA (1988) A population-based case-control study of diet and breast cancer in Australia. Am J Epidemiol 128(3):478–489

    PubMed  CAS  Google Scholar 

  59. Rohan TE, Howe GR, Friedenreich CM, Jain M, Miller AB (1993) Dietary fiber, vitamins A, C, and E, and risk of breast cancer: a cohort study. Cancer Causes Control 4(1):29–37

    Article  PubMed  CAS  Google Scholar 

  60. Verhoeven DT, Assen N, Goldbohm RA, Dorant E, van’t Veer P, Sturmans F, Hermus RJ, van den Brandt PA (1997) Vitamins C and E, retinol, beta-carotene and dietary fibre in relation to breast cancer risk: a prospective cohort study. Br J Cancer 75(1):149–155

    Article  PubMed  CAS  Google Scholar 

  61. 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(2):165–174

    PubMed  CAS  Google Scholar 

  62. Hunter DJ, Manson JE, Colditz GA, Stampfer MJ, Rosner B, Hennekens CH, Speizer FE, Willett WC (1993) A prospective study of the intake of vitamins C, E, and A and the risk of breast cancer. N Engl J Med 329(4):234–240

    Article  PubMed  CAS  Google Scholar 

  63. Graham S, Zielezny M, Marshall J, Priore R, Freudenheim J, Brasure J, Haughey B, Nasca P, Zdeb M (1992) Diet in the epidemiology of postmenopausal breast cancer in the New York State Cohort. Am J Epidemiol 136(11):1327–1337

    PubMed  CAS  Google Scholar 

  64. Shibata A, Paganini-Hill A, Ross RK, Henderson BE (1992) Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: a prospective study. Br J Cancer 66(4):673–679

    Article  PubMed  CAS  Google Scholar 

  65. Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE (2005) Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. Jama 294(1):56–65

    Article  PubMed  CAS  Google Scholar 

  66. Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JM, Ross C, Arnold A, Sleight P, Probstfield J et al (2005) Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 293(11):1338–1347

    Article  PubMed  Google Scholar 

  67. Lin J, Cook NR, Albert C, Zaharris E, Gaziano JM, Van Denburgh M, Buring JE, Manson JE (2009) Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial. J Natl Cancer Inst 101(1):14–23

    PubMed  CAS  Google Scholar 

  68. Gower JD (1988) A role for dietary lipids and antioxidants in the activation of carcinogens. Free Radic Biol Med 5(2):95–111

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Thanks J. Love for reviewing the paper.

Conflict of interest

All authors read and approved the final manuscript. None of the authors had any conflicts of interest.

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Authors and Affiliations

  1. Department of Epidemiology, Public Health College, Harbin Medical University, 157, Baojian Street, Nangang District, Harbin, Heilongjiang, People’s Republic of China

    Hu Fulan, Wang Yi Baina, Zhang Wencui, Lin Chunqing, Wang Fan, Li Dandan & Zhao Yashuang

  2. Center for Endemic Disease Control, Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China

    Jiang Changxing, Sun Dianjun & Wang Tong

  3. Department of Breast Surgery, Third Affiliated Clinical Hospital of Harbin Medical University, 150, Haping Street, Nangang District, Harbin, Heilongjiang Province, People’s Republic of China

    Pang Da

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  1. Hu Fulan
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Correspondence to Pang Da or Zhao Yashuang.

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Fulan, H., Changxing, J., Baina, W.Y. et al. Retinol, vitamins A, C, and E and breast cancer risk: a meta-analysis and meta-regression. Cancer Causes Control 22, 1383–1396 (2011). https://doi.org/10.1007/s10552-011-9811-y

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