Tofu intake is inversely associated with risk of breast cancer: A meta-analysis of observational studies

Autoři: Qianghui Wang aff001;  Xingming Liu aff001;  Shengqiang Ren aff001
Působiště autorů: Department of Urology, No. 906 Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Ningbo, China aff001
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article


Observational studies on the association between tofu intake and breast cancer incidence have reported inconsistent results. We reviewed the current evidence and quantitatively assessed this association by conducting a dose-response meta-analysis. The electronic databases PubMed and EMBASE were searched for relevant studies published up to August, 2018. We included epidemiological studies that reported relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for the association between tofu intake and breast cancer risk. A total of 14 studies (2 cohort studies, 12 case-control studies) were included in the meta-analysis. The overall OR of breast cancer for highest vs lowest intake of tofu was 0.78 (95% CI 0.69–0.88), with moderate heterogeneity (P = 0.011, I2 = 49.7%). Dose-response analysis based on 5 case-control studies revealed that each 10 g/d increase in tofu intake was associated with 10% reduction in the risk of breast cancer (95% CI 7%–13%, P = 0.037, I2 = 40.8%). In summary, our findings suggest an inverse dose-response association between tofu intake and risk of breast cancer. However, owing to the limitations of case-control studies, more properly designed prospective studies are warranted to confirm this association.

Klíčová slova:

Breast cancer – Case-control studies – Database searching – Histology – Menarche – Menopause – Metaanalysis – Smoking habits


1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA: a cancer journal for clinicians. 2015;65(2):87–108. doi: 10.3322/caac.21262 25651787.

2. Winters S, Martin C, Murphy D, Shokar NK. Breast Cancer Epidemiology, Prevention, and Screening. Progress in molecular biology and translational science. 2017;151:1–32. doi: 10.1016/bs.pmbts.2017.07.002 29096890.

3. Mourouti N, Kontogianni MD, Papavagelis C, Panagiotakos DB. Diet and breast cancer: a systematic review. International journal of food sciences and nutrition. 2015;66(1):1–42. doi: 10.3109/09637486.2014.950207 25198160.

4. Vera-Ramirez L, Ramirez-Tortosa MC, Sanchez-Rovira P, Ramirez-Tortosa CL, Granados-Principal S, Lorente JA, et al. Impact of diet on breast cancer risk: a review of experimental and observational studies. Critical reviews in food science and nutrition. 2013;53(1):49–75. doi: 10.1080/10408398.2010.521600 23035920.

5. Wiseman M. The second World Cancer Research Fund/American Institute for Cancer Research expert report. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. The Proceedings of the Nutrition Society. 2008;67(3):253–6. doi: 10.1017/S002966510800712X 18452640.

6. Messina M, Nagata C, Wu AH. Estimated Asian adult soy protein and isoflavone intakes. Nutr Cancer. 2006;55(1):1–12. doi: 10.1207/s15327914nc5501_1 16965235.

7. Shimizu H, Ross RK, Bernstein L, Yatani R, Henderson BE, Mack TM. Cancers of the prostate and breast among Japanese and white immigrants in Los Angeles County. Br J Cancer. 1991;63(6):963–6. doi: 10.1038/bjc.1991.210 2069852; PubMed Central PMCID: PMC1972548.

8. Zhong XS, Ge J, Chen SW, Xiong YQ, Ma SJ, Chen Q. Association between Dietary Isoflavones in Soy and Legumes and Endometrial Cancer: A Systematic Review and Meta-Analysis. Journal of the Academy of Nutrition and Dietetics. 2016. doi: 10.1016/j.jand.2016.09.036 27914914.

9. Zhang HY, Cui J, Zhang Y, Wang ZL, Chong T, Wang ZM. Isoflavones and Prostate Cancer: A Review of Some Critical Issues. Chinese medical journal. 2016;129(3):341–7. doi: 10.4103/0366-6999.174488 26831238; PubMed Central PMCID: PMC4799580.

10. Fritz H, Seely D, Flower G, Skidmore B, Fernandes R, Vadeboncoeur S, et al. Soy, red clover, and isoflavones and breast cancer: a systematic review. PLoS One. 2013;8(11):e81968. doi: 10.1371/journal.pone.0081968 24312387; PubMed Central PMCID: PMC3842968.

11. Wu AH, Yu MC, Tseng CC, Pike MC. Epidemiology of soy exposures and breast cancer risk. Br J Cancer. 2008;98(1):9–14. doi: 10.1038/sj.bjc.6604145 18182974; PubMed Central PMCID: PMC2359677.

12. Dong JY, Qin LQ. Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies. Breast Cancer Res Treat. 2011;125(2):315–23. doi: 10.1007/s10549-010-1270-8 21113655.

13. Nishio K, Niwa Y, Toyoshima H, Tamakoshi K, Kondo T, Yatsuya H, et al. Consumption of soy foods and the risk of breast cancer: findings from the Japan Collaborative Cohort (JACC) Study. Cancer Causes Control. 2007;18(8):801–8. Epub 2007/07/10. doi: 10.1007/s10552-007-9023-7 17619154.

14. Shu XO, Jin F, Dai Q, Wen W, Potter JD, Kushi LH, et al. Soyfood intake during adolescence and subsequent risk of breast cancer among Chinese women. Cancer Epidemiol Biomarkers Prev. 2001;10(5):483–8. Epub 2001/05/16. 11352858.

15. Kim MK, Kim JH, Nam SJ, Ryu S, Kong G. Dietary intake of soy protein and tofu in association with breast cancer risk based on a case-control study. Nutr Cancer. 2008;60(5):568–76. Epub 2008/09/16. doi: 10.1080/01635580801966203 [pii]. 18791919.

16. Cho YA, Kim J, Park KS, Lim SY, Shin A, Sung MK, et al. Effect of dietary soy intake on breast cancer risk according to menopause and hormone receptor status. Eur J Clin Nutr. 2010;64(9):924–32. Epub 2010/06/24. doi: 10.1038/ejcn.2010.95 [pii]. 20571498.

17. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Annals of internal medicine. 2009;151(4):264–9, W64. doi: 10.7326/0003-4819-151-4-200908180-00135 19622511.

18. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. Journal of the National Cancer Institute. 1959;22(4):719–48. Epub 1959/04/01. 13655060.

19. DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled clinical trials. 1986;7(3):177–88. Epub 1986/09/01. 0197-2456(86)90046-2 [pii]. doi: 10.1016/0197-2456(86)90046-2 3802833.

20. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Bmj. 2003;327(7414):557–60. doi: 10.1136/bmj.327.7414.557 12958120; PubMed Central PMCID: PMC192859.

21. Bax L, Ikeda N, Fukui N, Yaju Y, Tsuruta H, Moons KG. More than numbers: the power of graphs in meta-analysis. Am J Epidemiol. 2009;169(2):249–55. doi: 10.1093/aje/kwn340 19064649.

22. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088–101. 7786990.

23. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Bmj. 1997;315(7109):629–34. doi: 10.1136/bmj.315.7109.629 9310563; PubMed Central PMCID: PMC2127453.

24. Orsini N, Li R, Wolk A, Khudyakov P, Spiegelman D. Meta-analysis for linear and nonlinear dose-response relations: examples, an evaluation of approximations, and software. Am J Epidemiol. 2012;175(1):66–73. doi: 10.1093/aje/kwr265 22135359; PubMed Central PMCID: PMC3244608.

25. Greenland S. A meta-analysis of coffee, myocardial infarction, and coronary death. Epidemiology. 1993;4(4):366–74. Epub 1993/07/01. doi: 10.1097/00001648-199307000-00013 8347748.

26. Hirose K, Tajima K, Hamajima N, Inoue M, Takezaki T, Kuroishi T, et al. A large-scale, hospital-based case-control study of risk factors of breast cancer according to menopausal status. Japanese journal of cancer research: Gann. 1995;86(2):146–54. doi: 10.1111/j.1349-7006.1995.tb03032.x 7730137; PubMed Central PMCID: PMC5920764.

27. Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S, Japan Public Health Center-Based Prospective Study on Cancer Cardiovascular Diseases G. Soy, isoflavones, and breast cancer risk in Japan. J Natl Cancer Inst. 2003;95(12):906–13. doi: 10.1093/jnci/95.12.906 12813174.

28. Cui X, Dai Q, Tseng M, Shu XO, Gao YT, Zheng W. Dietary patterns and breast cancer risk in the shanghai breast cancer study. Cancer Epidemiol Biomarkers Prev. 2007;16(7):1443–8. doi: 10.1158/1055-9965.EPI-07-0059 17623805.

29. Travis RC, Allen NE, Appleby PN, Spencer EA, Roddam AW, Key TJ. A prospective study of vegetarianism and isoflavone intake in relation to breast cancer risk in British women. Int J Cancer. 2008;122(3):705–10. doi: 10.1002/ijc.23141 17943732.

30. Zhu YY, Zhou L, Jiao SC, Xu LZ. Relationship between soy food intake and breast cancer in China. Asian Pacific journal of cancer prevention: APJCP. 2011;12(11):2837–40. 22393950.

31. Zhang YF, Kang HB, Li BL, Zhang RM. Positive effects of soy isoflavone food on survival of breast cancer patients in China. Asian Pacific journal of cancer prevention: APJCP. 2012;13(2):479–82. doi: 10.7314/apjcp.2012.13.2.479 22524810.

32. Ko KP, Kim SW, Ma SH, Park B, Ahn Y, Lee JW, et al. Dietary intake and breast cancer among carriers and noncarriers of BRCA mutations in the Korean Hereditary Breast Cancer Study. Am J Clin Nutr. 2013;98(6):1493–501. doi: 10.3945/ajcn.112.057760 24153343.

33. Link LB, Canchola AJ, Bernstein L, Clarke CA, Stram DO, Ursin G, et al. Dietary patterns and breast cancer risk in the California Teachers Study cohort. Am J Clin Nutr. 2013;98(6):1524–32. doi: 10.3945/ajcn.113.061184 24108781; PubMed Central PMCID: PMC3831538.

34. Morimoto Y, Maskarinec G, Park SY, Ettienne R, Matsuno RK, Long C, et al. Dietary isoflavone intake is not statistically significantly associated with breast cancer risk in the Multiethnic Cohort. The British journal of nutrition. 2014;112(6):976–83. doi: 10.1017/S0007114514001780 25201305; PubMed Central PMCID: PMC4237401.

35. Baglia ML, Zheng W, Li H, Yang G, Gao J, Gao YT, et al. The association of soy food consumption with the risk of subtype of breast cancers defined by hormone receptor and HER2 status. Int J Cancer. 2016;139(4):742–8. doi: 10.1002/ijc.30117 27038352; PubMed Central PMCID: PMC5114023.

36. Kojima R, Okada E, Ukawa S, Mori M, Wakai K, Date C, et al. Dietary patterns and breast cancer risk in a prospective Japanese study. Breast cancer. 2017;24(1):152–60. doi: 10.1007/s12282-016-0689-0 26993124.

37. Key TJ, Sharp GB, Appleby PN, Beral V, Goodman MT, Soda M, et al. Soya foods and breast cancer risk: a prospective study in Hiroshima and Nagasaki, Japan. Br J Cancer. 1999;81(7):1248–56. Epub 1999/12/10. doi: 10.1038/sj.bjc.6690837 10584890; PubMed Central PMCID: PMC2374337.

38. Wu AH, Ziegler RG, Horn-Ross PL, Nomura AM, West DW, Kolonel LN, et al. Tofu and risk of breast cancer in Asian-Americans. Cancer Epidemiol Biomarkers Prev. 1996;5(11):901–6. Epub 1996/11/01. 8922298.

39. Do MH, Lee SS, Jung PJ, Lee MH. Intake of fruits, vegetables, and soy foods in relation to breast cancer risk in Korean women: a case-control study. Nutr Cancer. 2007;57(1):20–7. Epub 2007/05/23. doi: 10.1080/01635580701268063 17516859.

40. Hirose K, Imaeda N, Tokudome Y, Goto C, Wakai K, Matsuo K, et al. Soybean products and reduction of breast cancer risk: a case-control study in Japan. Br J Cancer. 2005;93(1):15–22. Epub 2005/06/09. 6602659 [pii] doi: 10.1038/sj.bjc.6602659 15942624; PubMed Central PMCID: PMC2361487.

41. Hirose K, Takezaki T, Hamajima N, Miura S, Tajima K. Dietary factors protective against breast cancer in Japanese premenopausal and postmenopausal women. Int J Cancer. 2003;107(2):276–82. Epub 2003/09/02. doi: 10.1002/ijc.11373 12949807.

42. Horn-Ross PL, John EM, Lee M, Stewart SL, Koo J, Sakoda LC, et al. Phytoestrogen consumption and breast cancer risk in a multiethnic population: the Bay Area Breast Cancer Study. Am J Epidemiol. 2001;154(5):434–41. Epub 2001/09/05. doi: 10.1093/aje/154.5.434 11532785.

43. Suzuki T, Matsuo K, Tsunoda N, Hirose K, Hiraki A, Kawase T, et al. Effect of soybean on breast cancer according to receptor status: a case-control study in Japan. Int J Cancer. 2008;123(7):1674–80. Epub 2008/07/16. doi: 10.1002/ijc.23644 18623079.

44. Witte JS, Ursin G, Siemiatycki J, Thompson WD, Paganini-Hill A, Haile RW. Diet and premenopausal bilateral breast cancer: a case-control study. Breast Cancer Res Treat. 1997;42(3):243–51. Epub 1997/02/01. doi: 10.1023/a:1005710211184 9065608.

45. Wu AH, Wan P, Hankin J, Tseng CC, Yu MC, Pike MC. Adolescent and adult soy intake and risk of breast cancer in Asian-Americans. Carcinogenesis. 2002;23(9):1491–6. Epub 2002/08/22. doi: 10.1093/carcin/23.9.1491 12189192.

46. Zaineddin AK, Buck K, Vrieling A, Heinz J, Flesch-Janys D, Linseisen J, et al. The association between dietary lignans, phytoestrogen-rich foods, and fiber intake and postmenopausal breast cancer risk: a German case-control study. Nutr Cancer. 2012;64(5):652–65. Epub 2012/05/18. doi: 10.1080/01635581.2012.683227 22591208.

47. Qin LQ, Xu JY, Wang PY, Hoshi K. Soyfood intake in the prevention of breast cancer risk in women: a meta-analysis of observational epidemiological studies. Journal of nutritional science and vitaminology. 2006;52(6):428–36. doi: 10.3177/jnsv.52.428 17330506.

48. Zhao TT, Jin F, Li JG, Xu YY, Dong HT, Liu Q, et al. Dietary isoflavones or isoflavone-rich food intake and breast cancer risk: A meta-analysis of prospective cohort studies. Clinical nutrition. 2019;38(1):136–45. doi: 10.1016/j.clnu.2017.12.006 29277346.

49. Messina M. Impact of Soy Foods on the Development of Breast Cancer and the Prognosis of Breast Cancer Patients. Forschende Komplementarmedizin. 2016;23(2):75–80. doi: 10.1159/000444735 27161216.

50. Cappelletti V, Fioravanti L, Miodini P, Di Fronzo G. Genistein blocks breast cancer cells in the G(2)M phase of the cell cycle. Journal of cellular biochemistry. 2000;79(4):594–600. 10996850.

51. Kousidou O, Tzanakakis GN, Karamanos NK. Effects of the natural isoflavonoid genistein on growth, signaling pathways and gene expression of matrix macromolecules by breast cancer cells. Mini reviews in medicinal chemistry. 2006;6(3):331–7. doi: 10.2174/138955706776073420 16515472.

52. Liu G, Hu X, Chakrabarty S. Calcium sensing receptor down-regulates malignant cell behavior and promotes chemosensitivity in human breast cancer cells. Cell calcium. 2009;45(3):216–25. doi: 10.1016/j.ceca.2008.10.004 19038444.

53. Hidayat K, Chen GC, Zhang R, Du X, Zou SY, Shi BM, et al. Calcium intake and breast cancer risk: meta-analysis of prospective cohort studies. The British journal of nutrition. 2016;116(1):158–66. doi: 10.1017/S0007114516001768 27170091.

54. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5. doi: 10.1007/s10654-010-9491-z 20652370.

55. Losilla JM, Oliveras I, Marin-Garcia JA, Vives J. Three risk of bias tools lead to opposite conclusions in observational research synthesis. Journal of clinical epidemiology. 2018;101:61–72. doi: 10.1016/j.jclinepi.2018.05.021 29864541.

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