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Comparison between the impact of fermented and unfermented soy intake on the risk of liver cancer: the JPHC Study

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Abstract

Purpose

The aim of this study was to compare the impact of fermented and unfermented soy intake, based on the following soy-derived products: tofu, soymilk, natto, and miso, on the risk of liver cancer among Japanese adults.

Methods

75,089 Participants of the Japan Public Health Center-based Prospective Study (JPHC Study) were followed from the time of the 5-year follow-up questionnaire until the end of 2012–2013. Subjects with available data on hepatitis B virus (HBV) and hepatitis C virus (HCV) infection status from blood samples (n = 14,016) and those who were anti-HCV antibody (anti-HCV) or hepatitis B virus antigen (HBsAg) positive (n = 1033) were also analyzed separately. Cox proportional hazard models were employed to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs).

Results

During 1,145,453 person-years, 534 newly diagnosed cases of liver cancer were identified in the JPHC Study. For miso intake among men, the multivariate-adjusted highest versus lowest quartile HR was 0.65 (95% CI, 0.48–0.89); p for trend = 0.006. Results were similar in those who were anti-HCV or HBsAg positive, 0.24 (0.08–0.70); p for trend = 0.004 highest versus lowest tertile. For the sub-analysis among only participants with known hepatitis infection status and HCV and HBsAg adjustment, a similar association was observed. In the multivariate complete cohort analysis, among women, the highest intake of fried tofu was inversely associated with the risk of liver cancer, HR = 0.45 (0.26–0.80); p for trend = 0.014.

Conclusions

We observed no association between total soy intake, fermented and unfermented, and risk of liver cancer, and only an inverse association between miso intake and liver cancer among men.

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Abbreviations

95% CI:

95% Confidence intervals

Anti-HCV:

Anti-HCV antibody

BMI:

Body mass index

DCO:

Death certificate only

FFQ:

Food frequency questionnaire

HBV:

Hepatitis B virus

HBsAg:

Hepatitis B virus antigen

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

HR:

Hazard ratio

JPHC Study:

Japan Public Health Center-based Prospective Study

PHC:

Public health center

R-PHA:

Passive hemagglutination

anti-HBc:

Hepatitis B core antigen

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Funding

This study was supported by the National Cancer Center Research and Development Fund (29-A-4, 26-A-2, 23-A-31 [toku]) (since 2011), a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare in Japan (from 1989 to 2010), and a grant from the Ministry of Agriculture, Fishery and Forestry of Japan (MAFF-CPS-2016-1-1). No relevant conflicts of interest exist.

Author information

Authors and Affiliations

  1. Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan

    Sarah Krull Abe, Norie Sawada, Junko Ishihara, Nagisa Mori, Taiki Yamaji, Taichi Shimazu, Atsushi Goto, Motoki Iwasaki, Manami Inoue & Shoichiro Tsugane

  2. Department of Food and Life Science, Azabu University, Kanagawa, Japan

    Junko Ishihara

  3. Department of Food Science and Nutrition, Faculty of Human Life and Environment, Nara Women’s University, Nara, Japan

    Ribeka Takachi

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  1. Sarah Krull Abe
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Consortia

for the JPHC Study Group

Contributions

MI* designed the study and checked the paper for consistency. SKA analyzed the data, generated the tables, and drafted the manuscript. NM, JI, and RT helped with the nutritional aspects of the study. NS, TY, TS, AG, MI*, MI, and ST substantially contributed to the interpretation of the results.

Corresponding author

Correspondence to Manami Inoue.

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Conflict of interest

The authors have no potential financial, personal, or other conflicts of interests.

Additional information

Research group members are listed at the following site (as of May, 2019): https://epi.ncc.go.jp/en/jphc/781/8233.html

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Abe, S.K., Sawada, N., Ishihara, J. et al. Comparison between the impact of fermented and unfermented soy intake on the risk of liver cancer: the JPHC Study. Eur J Nutr 60, 1389–1401 (2021). https://doi.org/10.1007/s00394-020-02335-9

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  • DOI: https://doi.org/10.1007/s00394-020-02335-9

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