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Soy and isoflavone consumption and risk of gastrointestinal cancer: a systematic review and meta-analysis

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Abstract

Purpose

Evidence suggests that soy foods have chemoprotective properties that may reduce the risk of certain cancers such as breast and prostate cancer. However, data involving gastrointestinal (GI) have been limited, and the evidence remains controversial. This study aims to determine the potential relationship between dietary soy intake and GI cancer risk with an evaluation of the effects of isoflavone as an active soy constituent.

Methods

Relevant studies were identified after literature search via electronic databases through May 2014. Subgroup analysis for isoflavone intake (studies n = 10) was performed. Covariants including gender types, anatomical subsites and preparation methods were also evaluated. Pooled adjusted odds ratios (ORs) comparing highest and lowest categories of dietary pattern scores were calculated using a random effects model.

Results

Twenty-two case–control and 18 cohort studies were included for meta-analysis, which contained a total of 633,476 participants and 13,639 GI cancer cases. The combined OR was calculated as 0.93 (95 % CI 0.87–0.99; p value heterogeneity = 0.01), showing only a slight decrease in risk, the association was stronger for colon cancer (OR 0.92; 95 % CI 0.96–0.99; p value heterogeneity = 0.163) and colorectal cancer (CRC) (OR 0.92; 95 % CI 0.87–0.97; p value heterogeneity = 0.3). Subgroup analysis for isoflavone intake showed a statistically significant risk reduction with a risk estimate of 0.73 (95 % CI 0.59–0.92; p value heterogeneity = 0), and particularly for CRC (OR 0.76; 95 % CI 0.59–0.98; p value heterogeneity = 0).

Conclusion

This study provides evidence that soy intake as a food group is only associated with a small reduction in GI cancer risk. Separate analysis for dietary isoflavone intakes suggests a stronger inverse association.

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References

  1. Messina M, Bennink M (1998) Soyfoods, isoflavones and risk of colonic cancer: a review of the in vitro and in vivo data. Baillieres Clin Endocrinol Metab 12:707–728

    Article  CAS  Google Scholar 

  2. Wang H, Murphy PA (1994) Isoflavone content in commercial soybean foods. J Afric Food Chem 42:1666–1673

    Article  CAS  Google Scholar 

  3. Fotsis T, Pepper M, Adlercreutz H, Hase T, Montesano R, Schweigerer L (1995) Genistein, a dietary ingested isoflavonoid, inhibits cell proliferation and in vitro angiogenesis. J Nutr 125:790S–797S

    CAS  Google Scholar 

  4. Markovits J, Linassier C, Fosse P, Couprie J, Pierre J, Jacquemin-Sablon A, Saucier JM, Le Pecq JB, Larsen AK (1989) Inhibitory effects of the tyrosine kinase inhibitor genistein on mammalian DNA topoisomerase II. Cancer Res 49:5111–5117

    CAS  Google Scholar 

  5. Akiyama T, Ishida J, Nakagawa S, Ogawara H, Watanabe S, Itoh N, Shiyba M, Fukami Y (1987) Genistein, a specific inhibitor of tyrosine-specific kinase. J Biol Chem 25:5592–5595

    Google Scholar 

  6. Booth C, Hargreaves DF, Hadfield JA, McGown AT, Potten CS (1999) Isoflavones inhibit intestinal epithelial cell proliferation and induce apoptosis in vitro. Br J Cancer 80:1550–1557

    Article  CAS  Google Scholar 

  7. Yan L, Spitznagel EL, Bosland MC (2010) Soy consumption and colorectal cancer risk in humans: a meta-analysis. Cancer Epidemiol Biomarkers Prev 19:148–158

    Article  CAS  Google Scholar 

  8. Wu AH, Yang D, Pike MC (2000) A meta-analysis of soyfoods and risk of stomach cancer: the problem of potential confounders. Cancer Epidemiol Biomarkers Prev 9:1051–1058

    CAS  Google Scholar 

  9. Lechner D, Kallay E, Cross HS (2005) Phytoestrogens and colorectal cancer prevention. Vitam Horm 70:169–198

    Article  CAS  Google Scholar 

  10. Clinton S, Destree R, Anderson D (1979) 1,2-Dimethylhydrazube induced intestinal cancer in rats fed beef or soy protein. Nutr Rep Int 20:335–342

    CAS  Google Scholar 

  11. Reddy B, Narisawa T, Weisburger J (1976) Effect of a diet with high levels of protein and fat on colon carcinogenesis in F344 rats treated with 1,2-Dimethylhydrazine. J Nat Cancer Inst 57:1559–1566

    Google Scholar 

  12. Monsma D, Eghtedary K, Klurfeld D (1997) Colon cancer and aberrant crpy formation in ras fed different types of meat. FASEB J 11:A576

    Google Scholar 

  13. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA 283:2008–2012

    Article  CAS  Google Scholar 

  14. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  17. Zhou Y, Lee AS (1998) Mechanism for the suppression of the mammalian stress response by genistein, an anticancer phytoestrogen from soy. J Nat Cancer Inst 90:381–388

    Article  CAS  Google Scholar 

  18. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J, Writing Group for the Women’s Health Initiative I (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women’s health initiative randomized controlled trial. JAMA 288:321–333

    Article  CAS  Google Scholar 

  19. Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB (1994) Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet 7:536–540

    Article  CAS  Google Scholar 

  20. Bennink MR (2001) Dietary soy reduces colon carcinogenesis in human and rats. Soy and colon cancer. Adv Exp Med Biol 492:11–17

    Article  CAS  Google Scholar 

  21. Masaoka Y, Watanabe H, Katoh O, Ito A, Dohi K (1998) Effects of miso and NaCl on the development of colonic aberrant crypt foci induced by azoxymethane in F344 rats. Nutr Cancer 32:25–28

    Article  CAS  Google Scholar 

  22. Govers MJ, Lapre JA, De Vries HT, Van der Meer R (1993) Dietary soybean protein compared with casein damages colonic epithelium and stimulates colonic epithelial proliferation in rats. J Nutr 123:1709–1713

    CAS  Google Scholar 

  23. Hu JF, Zhang SF, Jia EM, Wang QQ, Liu SD, Liu YY, Wu YP, Cheng YT (1988) Diet and cancer of the stomach: a case–control study in China. Int J Cancer 41:331–335

    Article  CAS  Google Scholar 

  24. Kono S, Ikeda M, Tokudome S, Kuratsune M (1988) A case–control study of gastric cancer and diet in northern Kyushu, Japan. Jpn J Cancer Res 79:1067–1074

    Article  CAS  Google Scholar 

  25. You WC, Blot WJ, Chang YS, Ershow AG, Yang ZT, An Q, Henderson B, Xu GW, Fraumeni JF Jr, Wang TG (1988) Diet and high risk of stomach cancer in Shandong, China. Cancer Res 48:3518–3523

    CAS  Google Scholar 

  26. Kato I, Tominaga S, Ito Y, Kobayashi S, Yoshii Y, Matsuura A, Kameya A, Kano T (1990) A comparative case–control analysis of stomach cancer and atrophic gastritis. Cancer Res 50:6559–6564

    CAS  Google Scholar 

  27. Hoshiyama Y, Sasaba T (1992) A case–control study of stomach cancer and its relation to diet, cigarettes, and alcohol consumption in Saltama Prefecture, Japan. Cancer Causes Control 3:441–448

    Article  CAS  Google Scholar 

  28. Hoshiyama Y, Sekine T, Sasaba T (1993) A case–control study of colorectal cancer and its relation to diet, cigarettes, and alcohol consumption in Saitama Prefecture, Japan. Tohoku J Exp Med 171:153–165

    Article  CAS  Google Scholar 

  29. Inoue M, Tajima K, Hirose K, Kuroishi T, Gao CM, Kitoh T (1994) Life-style and subsite of gastric cancer–joint effect of smoking and drinking habits. Int J Cancer 56:494–499

    Article  CAS  Google Scholar 

  30. Inoue M, Tajima K, Hirose K, Hamajima N, Takezaki T, Hirai T, Kato T, Ohno Y (1995) Subsite-specific risk factors for colorectal cancer: a hospital-based case–control study in Japan. Cancer Causes Control 6:14–22

    Article  CAS  Google Scholar 

  31. Lee JK, Park BJ, Yoo KY, Ahn YO (1995) Dietary factors and stomach cancer: a case–control study in Korea. Int J Epidemiol 24:33–41

    Article  CAS  Google Scholar 

  32. Le Marchand L, Hankin JH, Wilkens LR, Kolonel LN, Englyst HN, Lyu LC (1997) Dietary fiber and colorectal cancer risk. Epidemiology 8:658–665

    Article  Google Scholar 

  33. Nishi M, Yoshida K, Hirata K, Miyake H (1997) Eating habits and colorectal cancer. Oncol Rep 4:995–998

    CAS  Google Scholar 

  34. Ji BT, Chow WH, Yang G, McLaughlin JK, Zheng W, Shu XO, Jin F, Gao RN, Gao YT, Fraumeni JF Jr (1998) Dietary habits and stomach cancer in Shanghai, China. Int J Cancer 76:659–664

    Article  CAS  Google Scholar 

  35. Gao CM, Takezaki T, Ding JH, Li MS, Tajima K (1999) Protective effect of allium vegetables against both esophageal and stomach cancer: a simultaneous case-referent study of a high-epidemic area in Jiangsu Province, China. Jpn J Cancer Res 90:614–621

    Article  CAS  Google Scholar 

  36. Huang XE, Hirose K, Wakai K, Matsuo K, Ito H, Xiang J, Takezaki T, Tajima K (2004) Comparison of lifestyle risk factors by family history for gastric, breast, lung and colorectal cancer. APJCP 5:419–427

    Google Scholar 

  37. Ravasco P, Monteiro-Grillo I, Marques Vidal P, Camilo M (2005) Nutritional risks and colorectal cancer in a Portuguese population. Nutr Hosp 20:165–172

    CAS  Google Scholar 

  38. Cotterchio M, Boucher BA, Manno M, Gallinger S, Okey A, Harper P (2006) Dietary phytoestrogen intake is associated with reduced colorectal cancer risk. J Nutr 136:3046–3053

    CAS  Google Scholar 

  39. Ho SY, Schooling M, Hui LL, McGhee SM, Mak KH, Lam TH (2006) Soy consumption and mortality in Hong Kong: proxy-reported case–control study of all older adult deaths in 1998. Prev Med 43:20–26

    Article  Google Scholar 

  40. Rossi M, Negri E, Talamini R, Bosetti C, Parpinel M, Gnagnarella P, Franceschi S, Dal Maso L, Montella M, Giacosa A, La Vecchia C (2006) Flavonoids and colorectal cancer in Italy. Cancer Epidemiol Biomarkers Prev 15:1555–1558

    Article  CAS  Google Scholar 

  41. Williams CD, Satia JA, Adair LS, Stevens J, Galanko J, Keku TO, Sandler RS (2009) Dietary patterns, food groups, and rectal cancer risk in Whites and African–Americans. Cancer Epidemiol Biomarkers Prev 18:1552–1561

    Article  CAS  Google Scholar 

  42. Zhang YW, Eom SY, Kim YD, Song YJ, Yun HY, Park JS, Youn SJ, Kim BS, Kim H, Hein DW (2009) Effects of dietary factors and the NAT2 acetylator status on gastric cancer in Koreans. Int J Cancer 125:139–145

    Article  CAS  Google Scholar 

  43. Ko KP, Park SK, Park B, Yang JJ, Cho LY, Kang C, Kim CS, Gwack J, Shin A, Kim Y, Kim J, Yang HK, Kang D, Chang SH, Shin HR, Yoo KY (2010) Isoflavones from phytoestrogens and gastric cancer risk: a nested case–control study within the Korean Multicenter Cancer Cohort. Cancer Epidemiol Biomarkers Prev 19:1292–1300

    Article  CAS  Google Scholar 

  44. Budhathoki S, Joshi AM, Ohnaka K, Yin G, Toyomura K, Kono S, Mibu R, Tanaka M, Kakeji Y, Maehara Y, Okamura T, Ikejiri K, Futami K, Maekawa T, Yasunami Y, Takenaka K, Ichimiya H, Terasaka R (2011) Soy food and isoflavone intake and colorectal cancer risk: the Fukuoka colorectal cancer study. Scand J Gastroenterol 46:165–172

    Article  CAS  Google Scholar 

  45. Nomura A, Grove JS, Stemmermann GN, Severson RK (1990) A prospective study of stomach cancer and its relation to diet, cigarettes, and alcohol consumption. Cancer Res 50:627–631

    CAS  Google Scholar 

  46. Kato I, Tominaga S, Matsumoto K (1992) A prospective study of stomach cancer among a rural Japanese population: a 6-year survey. Jpn J Cancer Res 83:568–575

    Article  CAS  Google Scholar 

  47. Inoue M, Tajima K, Kobayashi S, Suzuki T, Matsuura A, Nakamura T, Shirai M, Nakamura S, Inuzuka K, Tominaga S (1996) Protective factor against progression from atrophic gastritis to gastric cancer–data from a cohort study in Japan. Int J Cancer 66:309–314

    Article  CAS  Google Scholar 

  48. Galanis DJ, Kolonel LN, Lee J, Nomura A (1998) Intakes of selected foods and beverages and the incidence of gastric cancer among the Japanese residents of Hawaii: a prospective study. Int J Epidemiol 27:173–180

    Article  CAS  Google Scholar 

  49. Nagata C, Takatsuka N, Kawakami N, Shimizu H (2002) A prospective cohort study of soy product intake and stomach cancer death. Br J Cancer 87:31–36

    Article  CAS  Google Scholar 

  50. Ngoan LT, Mizoue T, Fujino Y, Tokui N, Yoshimura T (2002) Dietary factors and stomach cancer mortality. Br J Cancer 87:37–42

    Article  CAS  Google Scholar 

  51. Ito LS, Inoue M, Tajima K, Yamamura Y, Kodera Y, Hirose K, Takezaki T, Hamajima N, Kuroishi T, Tominaga S (2003) Dietary factors and the risk of gastric cancer among Japanese women: a comparison between the differentiated and non-differentiated subtypes. Ann Epidemiol 13:24–31

    Article  Google Scholar 

  52. Khan MM, Goto R, Kobayashi K, Suzumura S, Nagata Y, Sonoda T, Sakauchi F, Washio M, Mori M (2004) Dietary habits and cancer mortality among middle aged and older Japanese living in hokkaido, Japan by cancer site and sex. APJCP 5:58–65

    CAS  Google Scholar 

  53. Iso H, Kubota Y, Japan Collaborative Cohort Study for Evaluation of C (2007) Nutrition and disease in the Japan collaborative cohort study for evaluation of cancer (JACC). APJCP 8(Suppl):35–80

    Google Scholar 

  54. Sauvaget C, Lagarde F, Nagano J, Soda M, Koyama K, Kodama K (2005) Lifestyle factors, radiation and gastric cancer in atomic-bomb survivors (Japan). Cancer Causes Control 16:773–780

    Article  Google Scholar 

  55. Tokui N, Yoshimura T, Fujino Y, Mizoue T, Hoshiyama Y, Yatsuya H, Sakata K, Kondo T, Kikuchi S, Toyoshima H, Hayakawa N, Kubo T, Tamakoshi A, Group JS (2005) Dietary habits and stomach cancer risk in the JACC Study. J Epidemiol 15(Suppl 2):S98–S108

    Article  Google Scholar 

  56. Oba S, Nagata C, Shimizu N, Shimizu H, Kametani M, Takeyama N, Ohnuma T, Matsushita S (2007) Soy product consumption and the risk of colon cancer: a prospective study in Takayama, Japan. Nutr Cancer 57:151–157

    Article  CAS  Google Scholar 

  57. Akhter M, Inoue M, Kurahashi N, Iwasaki M, Sasazuki S, Tsugane S, Japan Public Health Center-Based Prospective Study G (2008) Dietary soy and isoflavone intake and risk of colorectal cancer in the Japan public health center-based prospective study. Cancer Epidemiol Biomarkers Prev 17:2128–2135

    Article  CAS  Google Scholar 

  58. Butler LM, Wang R, Koh WP, Yu MC (2008) Prospective study of dietary patterns and colorectal cancer among Singapore Chinese. Br J Cancer 99:1511–1516

    Article  CAS  Google Scholar 

  59. Yang G, Shu XO, Li H, Chow WH, Cai H, Zhang X, Gao YT, Zheng W (2009) Prospective cohort study of soy food intake and colorectal cancer risk in women. Am J Clin Nutr 89:577–583

    Article  CAS  Google Scholar 

  60. Hara A, Sasazuki S, Inoue M, Iwasaki M, Shimazu T, Sawada N, Yamaji T, Tsugane S, Japan Public Health Center-Based Prospective Study G (2012) Isoflavone intake and risk of gastric cancer: a population-based prospective cohort study in Japan. Am J Clin Nutr 95:147–154

    Article  CAS  Google Scholar 

  61. Ko KP, Park SK, Yang JJ, Ma SH, Gwack J, Shin A, Kim Y, Kang D, Chang SH, Shin HR, Yoo KY (2013) Intake of soy products and other foods and gastric cancer risk: a prospective study. J Epidemiol 23:337–343

    Article  Google Scholar 

  62. Kweon SS, Shu XO, Xiang Y, Cai H, Yang G, Ji BT, Li H, Gao YT, Zheng W, Epplein M (2013) Intake of specific nonfermented soy foods may be inversely associated with risk of distal gastric cancer in a Chinese population. J Nutr 143:1736–1742

    Article  CAS  Google Scholar 

  63. Willet WC, Howe GR, Kushi LH (1997) Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr 65:1220S–1228S

    Google Scholar 

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Tse, G., Eslick, G.D. Soy and isoflavone consumption and risk of gastrointestinal cancer: a systematic review and meta-analysis. Eur J Nutr 55, 63–73 (2016). https://doi.org/10.1007/s00394-014-0824-7

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  • DOI: https://doi.org/10.1007/s00394-014-0824-7

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