Skip to main content

Advertisement

Log in

Isoflavone and soy food intake and risk of lung cancer in never smokers: report from prospective studies in Japan and China

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

Evidence from several cohorts has suggested that a higher intake of isoflavone is associated with lower risk of lung cancer in never smokers, but the association has not been investigated by histologic type of lung cancer. Adenocarcinoma is a common histologic type found in never smokers. We hypothesized that a higher intake of isoflavone is associated with a lower risk of lung adenocarcinoma among never smokers. Here, we examined the associations of isoflavone and soy food intake with lung cancer and its histologic types in never smokers.

Methods

We performed a pooled analysis using data from the Japan Public Health Center-based Prospective Study, Shanghai Women’s Health Study and Shanghai Men’s Study with 147,296 never smokers aged 40–74 years with no history of cancer. During 1,990,040 person-years of follow-up, 1247 lung cancer cases were documented. Dietary isoflavone and soy food intake were assessed using a food-frequency questionnaire. Multivariable Cox proportional hazards models assessed the associations between isoflavone and soy intake with incidence of lung cancer by histologic type.

Results

A higher intake of dietary isoflavone and soy food were associated with reduced risk of lung adenocarcinoma. The multivariable hazard ratios (HRs) (95% CI) of risk of lung adenocarcinoma for the highest versus lowest intakes of isoflavone and soy food were 0.74 (0.60–0.92) and 0.78 (0.63–0.96), respectively. The multivariable HRs of risk of lung adenocarcinoma associated with each 10 mg/day increase in isoflavone and each 50 g/day increase in soy food intake were 0.81 (0.70–0.94) and 0.84 (0.73–0.96), respectively.

Conclusion

Higher intake of isoflavone and soy food was associated with lower risk of lung adenocarcinoma in never smokers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Data availability

For information on how to submit an application for gaining access to JPHC data and/or biospecimens, please follow the instructions at https://epi.ncc.go.jp/en/jphc/805/8155.html.

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492

    Article  Google Scholar 

  2. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90. https://doi.org/10.3322/caac.20107

    Article  Google Scholar 

  3. Couraud S, Zalcman G, Milleron B, Morin F, Souquet PJ (2012) Lung cancer in never smokers—a review. Eur J Cancer 48:1299–1311. https://doi.org/10.1016/j.ejca.2012.03.007

    Article  CAS  Google Scholar 

  4. Toyoda Y, Nakayama T, Ioka A, Tsukuma H (2008) Trends in lung cancer incidence by histological type in Osaka, Japan. Jpn J Clin Oncol 38:534–539. https://doi.org/10.1093/jjco/hyn072

    Article  Google Scholar 

  5. Sun S, Schiller JH, Gazdar AF (2007) Lung cancer in never smokers—a different disease. Nat Rev Cancer 7:778–790. https://doi.org/10.1038/nrc2190

    Article  CAS  Google Scholar 

  6. Dias M, Linhas R, Campainha S, Conde S, Barroso A (2017) Lung cancer in never-smokers—what are the differences? Acta Oncol 56:931–935. https://doi.org/10.1080/0284186x.2017.1287944

    Article  Google Scholar 

  7. Okazaki I, Ishikawa S, Ando W, Sohara Y (2016) Lung adenocarcinoma in never smokers: problems of primary prevention from aspects of susceptible genes and carcinogens. Anticancer Res 36:6207–6224. https://doi.org/10.1873/anticanres.11215

    Article  CAS  Google Scholar 

  8. Rudin CM, Avila-Tang E, Harris CC, Herman JG, Hirsch FR, Pao W, Schwartz AG, Vahakangas KH, Samet JM (2009) Lung cancer in never smokers: molecular profiles and therapeutic implications. Clin Cancer Res 15:5646–5661. https://doi.org/10.1158/1078-0432.ccr-09-0377

    Article  CAS  Google Scholar 

  9. Messina M (2016) Soy and health update: evaluation of the clinical and epidemiologic literature. Nutrients 8:754. https://doi.org/10.3390/nu8120754

    Article  Google Scholar 

  10. Gallo D, Zannoni GF, De Stefano I, Mosca M, Ferlini C, Mantuano E, Scambia G (2008) Soy phytochemicals decrease nonsmall cell lung cancer growth in female athymic mice. J Nutr 138:1360–1364. https://doi.org/10.1093/jn/138.7.1360

    Article  CAS  Google Scholar 

  11. Lian F, Bhuiyan M, Li YW, Wall N, Kraut M, Sarkar FH (1998) Genistein-induced G2-M arrest, p21WAF1 upregulation, and apoptosis in a non-small-cell lung cancer cell line. Nutr Cancer 31:184–191. https://doi.org/10.1080/01635589809514701

    Article  CAS  Google Scholar 

  12. Peterson G (1995) Evaluation of the biochemical targets of genistein in tumor cells. J Nutr 125(3 Suppl):784S-789S. https://doi.org/10.1093/jn/125.suppl_3.784S

    Article  CAS  Google Scholar 

  13. Wu SH, Liu Z (2013) Soy food consumption and lung cancer risk: a meta-analysis using a common measure across studies. Nutr Cancer 65:625–632. https://doi.org/10.1080/01635581.2013.795983

    Article  CAS  Google Scholar 

  14. Shimazu T, Inoue M, Sasazuki S, Iwasaki M, Sawada N, Yamaji T, Tsugane S, Group JS (2011) Plasma isoflavones and the risk of lung cancer in women: a nested case-control study in Japan. Cancer Epidemiol Biomarkers Prev 20:419–427. https://doi.org/10.1158/1055-9965.EPI-10-1025

    Article  CAS  Google Scholar 

  15. Li M, Cai Q, Gao YT, Franke AA, Zhang X, Zhao Y, Wen W, Lan Q, Rothman N, Shyr Y et al (2022) Phytoestrogens and lung cancer risk: a nested case-control study in never-smoking Chinese women. Am J Clin Nutr 115:643–651. https://doi.org/10.1093/ajcn/nqab358

    Article  Google Scholar 

  16. Toh CK, Gao F, Lim W, Leong S, Fong K, Yap S, Hsu A, Eng P, Koong H, Thirugnanam A et al (2006) Never-smokers with lung cancer: epidemiologic evidence of a distinct disease entity. J Clin Oncol 24:2245–2251. https://doi.org/10.1200/JCO.2005.04.8033

    Article  Google Scholar 

  17. Tsugane S, Sawada N (2014) The JPHC study: design and some findings on the typical Japanese diet. Jpn J Clin Oncol 44:777–782. https://doi.org/10.1093/jjco/hyu096

    Article  Google Scholar 

  18. Zheng W, Chow WH, Yang G, Jin F, Rothman N, Blair A, Li HL, Wen W, Ji BT, Li Q et al (2005) The Shanghai women’s health study: rationale, study design, and baseline characteristics. Am J Epidemiol 162:1123–1131. https://doi.org/10.1093/aje/kwi322

    Article  Google Scholar 

  19. Shu XO, Li H, Yang G, Gao J, Cai H, Takata Y, Zheng W, Xiang YB (2015) Cohort profile: the Shanghai men’s health study. Int J Epidemiol 44:810–818. https://doi.org/10.1093/ije/dyv013

    Article  Google Scholar 

  20. Seow A, Koh WP, Wang R, Lee HP, Yu MC (2009) Reproductive variables, soy intake, and lung cancer risk among nonsmoking women in the Singapore Chinese Health Study. Cancer Epidemiol Biomarkers Prev 18:821–827. https://doi.org/10.1158/1055-9965.epi-08-0892

    Article  CAS  Google Scholar 

  21. Shimazu T, Inoue M, Sasazuki S, Iwasaki M, Sawada N, Yamaji T, Tsugane S (2010) Isoflavone intake and risk of lung cancer: a prospective cohort study in Japan. Am J Clin Nutr 91:722–728. https://doi.org/10.3945/ajcn.2009.28161

    Article  CAS  Google Scholar 

  22. Yang G, Shu XO, Chow WH, Zhang X, Li HL, Ji BT, Cai H, Wu S, Gao YT, Zheng W (2012) Soy food intake and risk of lung cancer: evidence from the Shanghai women’s health study and a meta-analysis. Am J Epidemiol 176:846–855. https://doi.org/10.1093/aje/kws168

    Article  Google Scholar 

  23. Kimira M, Arai Y, Shimoi K, Watanabe S (1998) Japanese Intake of flavonoids and isoflavonoids from foods. J Epidemiol 8:168–175. https://doi.org/10.2188/jea.8.168

    Article  CAS  Google Scholar 

  24. Arai Y, Watanabe S, Kimira M, Shimoi K, Mochizuki R, Kinae N (2000) Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration. J Nutr 130:2243–2250. https://doi.org/10.1093/jn/130.9.2243

    Article  CAS  Google Scholar 

  25. Yamamoto S, Sobue T, Sasaki S, Kobayashi M, Arai Y, Uehara M, Adlercreutz H, Watanabe S, Takahashi T, Iitoi Y et al (2001) Validity and reproducibility of a self-administered food-frequency questionnaire to assess isoflavone intake in a Japanese population in comparison with dietary records and blood and urine isoflavones. J Nutr 131:2741–2747. https://doi.org/10.1093/jn/131.10.2741

    Article  CAS  Google Scholar 

  26. Yang G, Shu X-O, Li H, Chow W-H, Cai H, Zhang X, Gao Y-T, Zheng W (2009) Prospective cohort study of soy food intake and colorectal cancer risk in women. Am J Clin Nutr 89:577–583. https://doi.org/10.3945/ajcn.2008.26742

    Article  CAS  Google Scholar 

  27. Shu XO, Yang G, Jin F, Liu D, Kushi L, Wen W, Gao YT, Zheng W (2004) Validity and reproducibility of the food frequency questionnaire used in the Shanghai women’s health study. Eur J Clin Nutr 58:17–23. https://doi.org/10.1038/sj.ejcn.1601738

    Article  CAS  Google Scholar 

  28. Willett W, Stampfer MJ (1986) Total energy intake: implications for epidemiologic analyses. Am J Epidemiol 124:17–27

    Article  CAS  Google Scholar 

  29. Ihira H, Sawada N, Yamaji T, Goto A, Shimazu T, Inoue M, Iwasaki M, Tsugane S, for the Japan Public Health Centre-based Prospective Study G (2019) Physical activity and subsequent risk of kidney, bladder and upper urinary tract cancer in the Japanese population: the Japan public health centre-based prospective study. Br J Cancer 120:571–574. https://doi.org/10.1038/s41416-019-0392-y

    Article  Google Scholar 

  30. Matthews CE, Shu X-O, Yang G, Jin F, Ainsworth BE, Liu D, Gao Y-T, Zheng W (2003) Reproducibility and validity of the Shanghai women’s health study physical activity questionnaire. Am J Epidemiol 158:1114–1122. https://doi.org/10.1093/aje/kwg255

    Article  Google Scholar 

  31. Fritz A, Percy C, Jack A, Shanmugaratnam K, Sobin LH et al (2000) International classification of diseases for oncology, 3rd edn. World Health Organization. https://apps.who.int/iris/handle/10665/42344

    Google Scholar 

  32. Travis WDCT, Corrin B, Shimosato Y, Brambilla E (1999) Histological typing of lung and pleural tumours, 3rd edn. Springer, Berlin

    Book  Google Scholar 

  33. Song J, Su H, Wang B, Zhou Y, Guo L (2014) Fish consumption and lung cancer risk: systematic review and meta-analysis. Nutr Cancer 66:539–549. https://doi.org/10.1080/01635581.2014.894102

    Article  CAS  Google Scholar 

  34. Zhong S, Ma Fau T, Chen L, Chen Fau L, Chen W, Chen Fau W, Lv M, Lv M, Zhang X, Zhang Fau X, Zhao J, Zhao J (2016) Physical activity and risk of lung cancer: a meta-analysis. Clin J Sport Med 26:173–181. https://doi.org/10.1097/JSM.0000000000000219

    Article  Google Scholar 

  35. Wang C, Yang T, Guo X-F, Li D (2019) The associations of fruit and vegetable intake with lung cancer risk in participants with different smoking status: a meta-analysis of prospective cohort studies. Nutrients 11:1791. https://doi.org/10.3390/nu11081791

    Article  Google Scholar 

  36. Zhu H, Zhang S (2018) Body mass index and lung cancer risk in never smokers: a meta-analysis. BMC Cancer 18:635–635. https://doi.org/10.1186/s12885-018-4543-y

    Article  CAS  Google Scholar 

  37. Yang WS, Wong MY, Vogtmann E, Tang RQ, Xie L, Yang YS, Wu QJ, Zhang W, Xiang YB (2012) Meat consumption and risk of lung cancer: evidence from observational studies. Ann Oncol 23:3163–3170. https://doi.org/10.1093/annonc/mds207

    Article  CAS  Google Scholar 

  38. Nitadori J, Inoue M, Iwasaki M, Otani T, Sasazuki S, Nagai K, Tsugane S (2006) Association between lung cancer incidence and family history of lung cancer: data from a large-scale population-based cohort study, the JPHC study. Chest 130:968–975. https://doi.org/10.1378/chest.130.4.968

    Article  Google Scholar 

  39. Cote ML, Liu M, Bonassi S, Neri M, Schwartz AG, Christiani DC, Spitz MR, Muscat JE, Rennert G, Aben KK et al (2012) Increased risk of lung cancer in individuals with a family history of the disease: a pooled analysis from the international lung cancer consortium. Eur J Cancer 48:1957–1968. https://doi.org/10.1016/j.ejca.2012.01.038

    Article  Google Scholar 

  40. Seow WJ, Shu XO, Nicholson JK, Holmes E, Walker DI, Hu W, Cai Q, Gao YT, Xiang YB, Moore SC et al (2019) Association of untargeted urinary metabolomics and lung cancer risk among never-smoking women in China. JAMA Netw Open 2:e1911970. https://doi.org/10.1001/jamanetworkopen.2019.11970

    Article  Google Scholar 

  41. Fan Y, Wang M, Li Z, Jiang H, Shi J, Shi X, Liu S, Zhao J, Kong L, Zhang W et al (2022) Intake of soy, soy isoflavones and soy protein and risk of cancer incidence and mortality. Front Nutr 9:847421. https://doi.org/10.3389/fnut.2022.847421

    Article  CAS  Google Scholar 

  42. Cutler GJ, Nettleton JA, Ross JA, Harnack LJ, Jacobs DR Jr, Scrafford CG, Barraj LM, Mink PJ, Robien K (2008) Dietary flavonoid intake and risk of cancer in postmenopausal women: the Iowa women’s health study. Int J Cancer 123:664–671. https://doi.org/10.1002/ijc.23564

    Article  CAS  Google Scholar 

  43. Rizzo G, Baroni L (2018) Soy, soy foods and their role in vegetarian diets. Nutrients 10:43. https://doi.org/10.3390/nu10010043

    Article  CAS  Google Scholar 

  44. Zou H, Zhan S, Cao K (2008) Apoptotic activity of genistein on human lung adenocarcinoma SPC-A-1 cells and preliminary exploration of its mechanisms using microarray. Biomed Pharmacother 62:583–589. https://doi.org/10.1016/j.biopha.2007.12.010

    Article  CAS  Google Scholar 

  45. Sasaki S, Ishihara J, Tsugane S (2003) Reproducibility of a self-administered food frequency questionnaire used in the 5-year follow-up survey of the JPHC study cohort I to assess food and nutrient intake. J Epidemiol 13:115–124. https://doi.org/10.2188/jea.13.1sup_115

    Article  Google Scholar 

  46. Ishihara J, Sobue T, Yamamoto S, Yoshimi I, Sasaki S, Kobayashi M, Takahashi T, Iitoi Y, Akabane M, Tsugane S (2003) Validity and reproducibility of a self-administered food frequency questionnaire in the JPHC study cohort II: study design, participant profile and results in comparison with cohort I. J Epidemiol 13:S134-147. https://doi.org/10.2188/jea.13.1sup_134

    Article  Google Scholar 

  47. Ministry of health, labour and welfare. The national health and nutrition survey in Japan. https://www.nibiohn.go.jp/eiken/kenkounippon21/en/eiyouchousa/keinen_henka_time.html. Accessed 13 Aug 2021

  48. Pronk A, Coble J, Ji BT, Shu XO, Rothman N, Yang G, Gao YT, Zheng W, Chow WH (2009) Occupational risk of lung cancer among lifetime non-smoking women in Shanghai. China Occup Environ Med 66:672. https://doi.org/10.1136/oem.2008.043695

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are indebted to the Aomori, Akita, Iwate, Niigata, Nagano, Ibaraki, Osaka, Kochi, Nagasaki and Okinawa Cancer Registries for providing their incidence data. JPHC members are listed at the following site (as of April 2019); https://epi.ncc.go.jp/en/jphc/781/8390.html

Funding

This work was supported by National Cancer Center Research and Development Fund (23-A-31[toku], 26-A-2, 29-A-4, 2020-J-4) (since 2011); a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan (from 1989 to 2010); and the National Institute of Health (NIH) (UM1 CA173640 and UM1 CA182910).

Author information

Authors and Affiliations

Authors

Contributions

NS, ST, MI, XOS and WZ contributed to study conception and designed the research. NS, ST, MI, TY, TS, MI, NKK, HC, XOS and WZ conducted the research. CLC and NS analyzed the data. The first draft of the manuscript was written by CLC and all the authors commented on previous versions of the manuscript. NS had primary responsibility for the final content. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Norie Sawada.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Ethical approval

The JPHC studies were approved by the institutional review board of the National Cancer Center, Japan. The SWHS and SMHS studies were approved by the institutional review boards for human research of both Shanghai Cancer Institute (China) and Vanderbilt University (United States).

Consent to participate

Informed consent was obtained from all the individual participants included in the study.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chei, CL., Sawada, N., Khankari, N.K. et al. Isoflavone and soy food intake and risk of lung cancer in never smokers: report from prospective studies in Japan and China. Eur J Nutr 62, 125–137 (2023). https://doi.org/10.1007/s00394-022-02968-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-022-02968-y

Keywords

Navigation