Breast Cancer Research and Treatment

, Volume 131, Issue 1, pp 239–253 | Cite as

Carotenoids and breast cancer risk: a meta-analysis and meta-regression

  • Fulan Hu
  • Baina Wang Yi
  • Wencui Zhang
  • Jing Liang
  • Chunqing Lin
  • Dandan Li
  • Fan Wang
  • Da PangEmail author
  • Yashuang ZhaoEmail author


The purpose of this article is to comprehensively summarize the associations between carotenoids and breast cancer and quantitatively estimate their dose–response relationships. We searched PubMed, Embase, and Cochrane databases (from January 1982 to 1 May 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 carotenoids. Two reviewers independently extracted data using a standardized form; with any discrepancy adjudicated by the third reviewer. 33 studies met the inclusion criteria. Comparing the highest with the lowest intake: dietary α-carotene intake significantly reduced the breast cancer risk by 9.0% (pooled RR = 0.91; 95% CI: 0.85–0.98; P = 0.01), dietary β-carotene intake reduced the risk by 6.0% (pooled RR = 0.94; 95% CI: 0.88–1.00; P = 0.05); total β-carotene intake reduced the risk by 5.0% (pooled RR = 0.95; 95% CI: 0.90–1.01; P = 0.08) when data from cohort studies were pooled. Significant dose–response relationships were observed in both the higher intake of dietary and total β-carotene with reduced breast cancer risk when data from cohort studies (P trend < 0.01, P trend = 0.03) and case–control studies (P trend < 0.01, P trend < 0.01) were pooled, respectively. Dietary α-carotene intake could reduce the breast cancer risk. The relationships between dietary and total β-carotene intake and breast cancer need to be confirmed. No significant association between dietary intake of β-cryptoxanthin, lutein/+zeaxanthin, and lycopene and breast cancer was observed.


Carotenoids Breast cancer Meta-analysis Meta-regression 



The authors thank 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.

Supplementary material

10549_2011_1723_MOESM1_ESM.doc (860 kb)
Supplementary material 1 (DOC 861 kb)


  1. 1.
  2. 2.
    Buell P (1973) Changing incidence of breast cancer in Japanese-American women. J Natl Cancer Inst 51(5):1479–1483PubMedGoogle Scholar
  3. 3.
    Thomas DB, Karagas MR (1987) Cancer in first and second generation Americans. Cancer Res 47(21):5771–5776PubMedGoogle Scholar
  4. 4.
    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):617–631PubMedCrossRefGoogle Scholar
  5. 5.
    Kelsey JL, Horn-Ross PL (1993) Breast cancer: magnitude of the problem and descriptive epidemiology. Epidemiol Rev 15(1):7–16PubMedGoogle Scholar
  6. 6.
    Chew BP, Brown CM, Park JS, Mixter PF (2003) Dietary lutein inhibits mouse mammary tumor growth by regulating angiogenesis and apoptosis. Anticancer Res 23(4):3333–3339PubMedGoogle Scholar
  7. 7.
    Cui Y, Lu Z, Bai L, Shi Z, Zhao WE, Zhao B (2007) Beta-carotene induces apoptosis and up-regulates peroxisome proliferator-activated receptor gamma expression and reactive oxygen species production in MCF-7 cancer cells. Eur J Cancer 43(17):2590–2601PubMedCrossRefGoogle Scholar
  8. 8.
    Wang AH, Zhang LS (2007) Effect of lycopene on the proliferation of MCF-7 and MDA-MB-231 cells. Sichuan Da Xue Xue Bao Yi Xue Ban 38(6):958–960, 976Google Scholar
  9. 9.
    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):636–646PubMedCrossRefGoogle Scholar
  10. 10.
    Druesne-Pecollo N, Latino-Martel P, Norat T, Barrandon E, Bertrais S, Galan P, Hercberg S (2010) Beta-carotene supplementation and cancer risk: a systematic review and metaanalysis of randomized controlled trials. Int J Cancer 127(1):172–184PubMedCrossRefGoogle Scholar
  11. 11.
    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):713–720PubMedGoogle Scholar
  12. 12.
    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):111–119PubMedCrossRefGoogle Scholar
  13. 13.
    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):23–29PubMedCrossRefGoogle Scholar
  14. 14.
    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):547–556PubMedCrossRefGoogle Scholar
  15. 15.
    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):131–137PubMedCrossRefGoogle Scholar
  16. 16.
    Levi F, Pasche C, Lucchini F, La Vecchia C (2001) Dietary intake of selected micronutrients and breast-cancer risk. Int J Cancer 91(2):260–263PubMedCrossRefGoogle Scholar
  17. 17.
    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):534–540PubMedGoogle Scholar
  18. 18.
    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):137–145PubMedCrossRefGoogle Scholar
  19. 19.
    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):737–747PubMedCrossRefGoogle Scholar
  20. 20.
    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):1009–1018PubMedGoogle Scholar
  21. 21.
    Terry P, Jain M, Miller AB, Howe GR, Rohan TE (2002) Dietary carotenoids and risk of breast cancer. Am J Clin Nutr 76(4):883–888PubMedGoogle Scholar
  22. 22.
    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):1485–1494PubMedGoogle Scholar
  23. 23.
    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):429–439PubMedCrossRefGoogle Scholar
  24. 24.
    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):2929–2937PubMedCrossRefGoogle Scholar
  25. 25.
    Nagel G, Linseisen J, van Gils CH, Peeters PH, Boutron-Ruault MC, Clavel-Chapelon F, Romieu I, Tjonneland A, Olsen A, Roswall N, Witt PM, Overvad K, Rohrmann S, Kaaks R, Drogan D, Boeing H, Trichopoulou A, Stratigakou V, Zylis D, Engeset D, Lund E, Skeie G, Berrino F, Grioni S, Mattiello A, Masala G, Tumino R, Zanetti R, Ros MM, Bueno-de-Mesquita HB, Ardanaz E, Sanchez MJ, Huerta JM, Amiano P, Rodriguez L, Manjer J, Wirfalt E, Lenner P, Hallmans G, Spencer EA, Key TJ, Bingham S, Khaw KT, Rinaldi S, Slimani N, Boffetta P, Gallo V, Norat T, Riboli E (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):753–765PubMedCrossRefGoogle Scholar
  26. 26.
    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):315–321PubMedCrossRefGoogle Scholar
  27. 27.
    Nkondjock A, Ghadirian P (2004) Intake of specific carotenoids and essential fatty acids and breast cancer risk in Montreal, Canada. Am J Clin Nutr 79(5):857–864PubMedGoogle Scholar
  28. 28.
    Huang JP, Zhang M, Holman CD, Xie X (2007) Dietary carotenoids and risk of breast cancer in Chinese women. Asia Pac J Clin Nutr 16(Suppl 1):437–442PubMedGoogle Scholar
  29. 29.
    Sesso HD, Buring JE, Zhang SM, Norkus EP, Gaziano JM (2005) Dietary and plasma lycopene and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev 14(5):1074–1081PubMedCrossRefGoogle Scholar
  30. 30.
    Larsson SC, Bergkvist L, Wolk A (2010) Dietary carotenoids and risk of hormone receptor-defined breast cancer in a prospective cohort of Swedish women. Eur J Cancer 46(6):1079–1085PubMedCrossRefGoogle Scholar
  31. 31.
    Berlin JA, Longnecker MP, Greenland S (1993) Meta-analysis of epidemiologic dose-response data. Epidemiology 4(3):218–228PubMedCrossRefGoogle Scholar
  32. 32.
    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):610–621PubMedGoogle Scholar
  33. 33.
    Trock BJ, Hilakivi-Clarke L, Clarke R (2006) Meta-analysis of soy intake and breast cancer risk. J Natl Cancer Inst 98(7):459–471PubMedCrossRefGoogle Scholar
  34. 34.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560PubMedCrossRefGoogle Scholar
  35. 35.
    Fleiss JL (1993) The statistical basis of meta-analysis. Stat Methods Med Res 2(2):121–145PubMedCrossRefGoogle Scholar
  36. 36.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634PubMedCrossRefGoogle Scholar
  37. 37.
    Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101PubMedCrossRefGoogle Scholar
  38. 38.
    Negri E, La Vecchia C, Franceschi S, D’Avanzo B, Talamini R, Parpinel M, Ferraroni M, Filiberti R, Montella M, Falcini F, Conti E, Decarli A (1996) Intake of selected micronutrients and the risk of breast cancer. Int J Cancer 65(2):140–144PubMedCrossRefGoogle Scholar
  39. 39.
    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):493–501PubMedCrossRefGoogle Scholar
  40. 40.
    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):1–9PubMedGoogle Scholar
  41. 41.
    Lee HP, Gourley L, Duffy SW, Esteve J, Lee J, Day NE (1991) Dietary effects on breast-cancer risk in Singapore. Lancet 337(8751):1197–1200PubMedCrossRefGoogle Scholar
  42. 42.
    Levi F, La Vecchia C, Gulie C, Negri E (1993) Dietary factors and breast cancer risk in Vaud, Switzerland. Nutr Cancer 19(3):327–335PubMedCrossRefGoogle Scholar
  43. 43.
    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):205–214PubMedCrossRefGoogle Scholar
  44. 44.
    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):340–348PubMedCrossRefGoogle Scholar
  45. 45.
    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):478–489PubMedGoogle Scholar
  46. 46.
    Van ‘t Veer P, Kolb CM, Verhoef P, Kok FJ, Schouten EG, Hermus RJ, Sturmans F (1990) Dietary fiber, beta-carotene and breast cancer: results from a case-control study. Int J Cancer 45(5):825–828PubMedCrossRefGoogle Scholar
  47. 47.
    Ewertz M, Gill C (1990) Dietary factors and breast-cancer risk in Denmark. Int J Cancer 46(5):779–784PubMedCrossRefGoogle Scholar
  48. 48.
    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):770–776PubMedCrossRefGoogle Scholar
  49. 49.
    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):149–155PubMedCrossRefGoogle Scholar
  50. 50.
    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):673–679PubMedCrossRefGoogle Scholar
  51. 51.
    Nishino H, Tokuda H, Murakoshi M, Satomi Y, Masuda M, Onozuka M, Yamaguchi S, Takayasu J, Tsuruta J, Okuda M, Khachik F, Narisawa T, Takasuka N, Yano M (2000) Cancer prevention by natural carotenoids. Biofactors 13(1–4):89–94PubMedCrossRefGoogle Scholar
  52. 52.
    Maillard V, Hoinard C, Arab K, Jourdan ML, Bougnoux P, Chajes V (2006) Dietary beta-carotene inhibits mammary carcinogenesis in rats depending on dietary alpha-linolenic acid content. Br J Nutr 96(1):18–21PubMedCrossRefGoogle Scholar
  53. 53.
    Reboul E, Thap S, Tourniaire F, Andre M, Juhel C, Morange S, Amiot MJ, Lairon D, Borel P (2007) Differential effect of dietary antioxidant classes (carotenoids, polyphenols, vitamins C and E) on lutein absorption. Br J Nutr 97(3):440–446PubMedCrossRefGoogle Scholar
  54. 54.
    Burgess LC, Rice E, Fischer T, Seekins JR, Burgess TP, Sticka SJ, Klatt K (2008) Lycopene has limited effect on cell proliferation in only two of seven human cell lines (both cancerous and noncancerous) in an in vitro system with doses across the physiological range. Toxicol In Vitro 22(5):1297–1300PubMedCrossRefGoogle Scholar
  55. 55.
    Gunasekera RS, Sewgobind K, Desai S, Dunn L, Black HS, McKeehan WL, Patil B (2007) Lycopene and lutein inhibit proliferation in rat prostate carcinoma cells. Nutr Cancer 58(2):171–177PubMedCrossRefGoogle Scholar
  56. 56.
    Nagasawa H, Mitamura T, Sakamoto S, Yamamoto K (1995) Effects of lycopene on spontaneous mammary tumour development in SHN virgin mice. Anticancer Res 15(4):1173–1178PubMedGoogle Scholar
  57. 57.
    Sharoni Y, Giron E, Rise M, Levy J (1997) Effects of lycopene-enriched tomato oleoresin on 7,12-dimethyl-benz[a]anthracene-induced rat mammary tumors. Cancer Detect Prev 21(2):118–123PubMedGoogle Scholar
  58. 58.
    Cohen LA, Zhao Z, Pittman B, Khachik F (1999) Effect of dietary lycopene on N-methylnitrosourea-induced mammary tumorigenesis. Nutr Cancer 34(2):153–159PubMedCrossRefGoogle Scholar
  59. 59.
    Musa-Veloso K, Card JW, Wong AW, Cooper DA (2009) Influence of observational study design on the interpretation of cancer risk reduction by carotenoids. Nutr Rev 67(9):527–545PubMedCrossRefGoogle Scholar
  60. 60.
    Duval S, Tweedie R (2000) Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56(2):455–463PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Fulan Hu
    • 1
  • Baina Wang Yi
    • 1
  • Wencui Zhang
    • 1
  • Jing Liang
    • 1
  • Chunqing Lin
    • 1
  • Dandan Li
    • 1
  • Fan Wang
    • 1
  • Da Pang
    • 2
    Email author
  • Yashuang Zhao
    • 1
    Email author
  1. 1.Department of Epidemiology, Public Health CollegeHarbin Medical UniversityHarbinPeople’s Republic of China
  2. 2.Department of Breast SurgeryCancer Hospital of Harbin Medical UniversityHarbinPeople’s Republic of China

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