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Independent and opposing associations of dietary phytosterols intake and PLCE1 rs2274223 polymorphisms on esophageal squamous cell carcinoma risk

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Abstract

Purpose

This study was to evaluate the associations of dietary intake of total and specific phytosterols and risk of esophageal squamous cell carcinoma (ESCC) and to explore their joint effects with PLCE1 rs2274223 polymorphisms.

Methods

A population-based case–control study was conducted in a Chinese rural population and 856 eligible incident ESCC cases and 856 controls were included. A validated food frequency questionnaire was used to collect dietary consumption and PLCE1 rs2274223 polymorphisms were genotyped. Unadjusted and adjusted odds ratios (ORs) with 95% confidence interval (CI) were assessed via logistic regression model.

Results

When comparing the highest with lowest intake quartiles, β-sitosterol, campesterol, stigmasterol, β-sitostanol, campestanol, and total phytosterols were all associated with a decreased risk of ESCC, with adjusted ORs being 0.32 (95% CI 0.20–0.48), 0.18 (95% CI 0.11–0.27), 0.45 (95% CI 0.29–0.70), 0.13 (95% CI 0.08–0.20), 0.14 (95% CI 0.09–0.22) and 0.28 (95% CI 0.18–0.43), respectively. An exposure—response relationship was also observed for both total and five specific phytosterols (all P for trend < 0.001). In comparison to rs2274223 AA genotype, both GA genotype (OR: 1.47, 95% CI 1.16–1.85) and GG genotype (OR: 2.13, 95% CI 1.20–3.84) were associated with an increased risk of ESCC. However, no interaction was observed between total/specific phytosterols intake and rs2274223 polymorphisms.

Conclusion

Higher dietary intake of total and five specific phytosterols was associated with a lower risk of ESCC, and the risk of ESCC increased with the increment of rs2274223 G allele. The negative association between phytosterols and ESCC risk was not modified by rs2274223 polymorphisms. Foods or supplements rich in phytosterols are a promising source for chemoprevention of ESCC, and still, clinical trials will be required in any specific case.

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Availability of data and materials

The data used to support the findings of this study are available from the corresponding author upon request.

Code availability

The code used to analyze the data are available from the corresponding author upon request.

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Acknowledgements

The authors provide great appreciation to Retired Professor Xiaorong Wang, winner of the World Cancer Research Fund, International (No. 2010/240), for her comments and outstanding research work. The authors would like to thank the epidemiologist, nurses, and doctors in the Yanting Cancer Hospital for their cooperation in data collection, and thank all study subjects for their participation.

Funding

The study was supported by the World Cancer Research Fund, International (No. 2010/240), the Guangdong Basic and Applied Basic Research Foundation (No. 2019A1515011599), National Natural Science Foundation of China (No. 81400857), Natural Science Foundation of Guangdong Province (No. 2017A030313697). The founders had no role in the design, analysis or writing of this manuscript.

Author information

Author notes

  1. Shuyi Wang and Wenjing Zhao are contributed equally.

Authors and Affiliations

  1. Department of Epidemiology, School of Public Health, Sun Yat-Sen University, 2F, Block 20, No.74, Zhongshan Second Road, Guangzhou, 510080, China

    Shuyi Wang, Liping Sun, Su-Mei Xiao, Yu-Ming Chen & Xudong Liu

  2. Department of Public Health, Faculty of Medicine, Hokkaido University, Sapporo, Japan

    Wenjing Zhao

  3. School of Management, Putian University, Putian, China

    Sihao Lin

  4. Shenzhen Center for Disease Control and Prevention, Shenzhen, China

    Jin Zhao

  5. Lab for Aging Research, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China

    Hengyi Xiao

  6. Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

    Xiangbin Xing

  7. JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, China

    Xiang Qian Lao

Authors
  1. Shuyi Wang
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  11. Xudong Liu
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Contributions

XL conceived and designed the study; SL, LS and JZ collected the data, SW and WZ analyzed the data and drafted the manuscript; HX, SX, XQL, XX, YC and XL reviewed and edited the manuscript. All co-authors provided read and approved the final version.

Corresponding author

Correspondence to Xudong Liu.

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Ethical approval

The study was approved by the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee and Ethical Review Committee for Biomedical Research, School of Public Health, Sun Yat-sen University. This study met the requirement of the guidelines laid down in the Declaration of Helsinki.

Conflicts of interest

The authors state that they have no conflicts of interest.

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Cite this article

Wang, S., Zhao, W., Sun, L. et al. Independent and opposing associations of dietary phytosterols intake and PLCE1 rs2274223 polymorphisms on esophageal squamous cell carcinoma risk. Eur J Nutr 60, 4357–4366 (2021). https://doi.org/10.1007/s00394-021-02561-9

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  • DOI: https://doi.org/10.1007/s00394-021-02561-9

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