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A diet-wide association study for liver cancer risk: findings from a prospective cohort study in Chinese men

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Abstract

Dietary factors have been extensively investigated as possible risk factors for liver cancer, but the evidence is inconclusive. Our study systematically assessed the association between 142 foods and nutrients and liver cancer risk in a Chinese population using a diet-wide association study. Based on data from 59,844 men in the Shanghai Men’s Health Study (SMHS), we assessed the diet intake by dietary questionnaires. Cox regression was used to quantify the association between each food and nutrient and liver cancer risk. A false discovery rate (FDR) of 0.05 was used to select the foods and nutrients for validation. In the cohort, 431 liver cancer cases were identified during 712,373 person-years of follow-up. Retinol (HR per 1 SD increment = 1.09, 95% CI: 1.03–1.14) was associated with a higher risk of liver cancer, whereas onions (HR per 1 SD increment = 0.67, 95% CI: 0.54–0.84) and manganese (HR per 1 SD increment = 0.85, 95% CI: 0.78–0.94) were inversely associated with liver cancer risk. In the replication analysis, estimates for these foods and nutrients were similar in magnitude and direction. Our findings confirm that retinol, onions and manganese were associated with liver cancer risk, which provides reliable evidence between diet and liver cancer development.

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Data availability

The data will be available on request pending approval by the scientific committee of the relevant institutes.

Abbreviations

PLC:

Primary liver cancer

HCC:

Hepatocellular carcinoma

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

T2DM:

Type 2 diabetes mellitus

MAFLD:

Metabolic associated fatty liver disease

WCRF:

World Cancer Research Fund

HPFS:

Health Professionals Follow-up Study

NHS:

Nurses’ Health Study

EPIC:

European Prospective Investigation into Cancer and Nutrition

SMHS:

Shanghai Men’s Health Study

DWAS:

Diet-wide association study

GWAS:

Genome-wide association study

FDR:

False discovery rate

FFQ:

Food frequency questionnaire

HR:

Hazard ratio

CI:

Confidence interval

PYs:

Person-years

BMI:

Body mass index

MET:

Metabolic equivalent

IQR:

Inter quartile range

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Acknowledgements

We thank all participants and staff from the Shanghai Men’s Health Study for their contribution to this research.

Funding

This work was supported by a grant from the National Key Project of Research and Development Program of China [2021YFC2500404 & 2021YFC2500405]; and the parent cohort was supported by a subcontract of grant from the US National Institutes of Health [UM1 CA182910]. All funders had no role in the design, analysis and writing of this article.

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Authors and Affiliations

  1. School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, P. R. China

    Jia-Yi Tuo

  2. State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 25, Lane 2200, Xie Tu Road, Shanghai, 200032, P. R. China

    Jia-Yi Tuo, Zhuo-Ying Li, Qiu-Ming Shen, Yu-Ting Tan, Hong-Lan Li & Yong-Bing Xiang

  3. School of Public Health, Fudan University, Shanghai, 200032, P. R. China

    Zhuo-Ying Li

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Contributions

Y-BX designed research and obtained funding; J-YT, Z-YL, Q-MS, Y-TT, H-LL, Y-BX conducted the study; J-YT, Y-BX analyzed the data and interpreted the results; J-YT and Y-BX prepared and wrote the first draft; All authors reviewed and approved the final version of the paper; and Y-BX has primary responsibility for final content.

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Correspondence to Yong-Bing Xiang.

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The cohort protocol has been approved by the Institutional Review Boards of the Shanghai Cancer Institute and Vanderbilt University. Informed consent has been obtained from all participants. The current study has been approved by the Renji Hospital Ethics Committee of Shanghai Jiao Tong University School of Medicine (KY2019-197).

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Tuo, JY., Li, ZY., Shen, QM. et al. A diet-wide association study for liver cancer risk: findings from a prospective cohort study in Chinese men. Eur J Epidemiol 39, 171–178 (2024). https://doi.org/10.1007/s10654-023-01071-8

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