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Risk of first onset of colorectal cancer associated with alcohol consumption in Lynch syndrome: a multicenter cohort study

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A Correction to this article was published on 19 April 2022

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Abstract

Background

Complex interactions among endogenous and exogenous factors influence the incidence of colorectal cancer (CRC). Germline mutations in mismatch repair (MMR) genes causing Lynch syndrome (LS) are major endogenous factors. The exogenous factor, alcohol consumption, is potentially associated with CRC incidence among patients with LS. However, insufficient data are available to determine whether alcohol consumption influences the time of the first onset of CRC associated with sex, MMR gene mutations, and anatomical tumor site.

Methods

Among 316 patients with LS identified in a Japanese LS cohort, we included 288 with data on age, sex, proband status, alcohol status, smoking status, tumor location, and MMR gene mutations. Multivariable analysis assessed the association of alcohol consumption with earlier onset of the first CRC.

Results

Ever drinkers were associated with higher risk of the first onset of CRC than never drinkers (HR 1.54, 95%CI 1.14–2.07, P = 0.004). The association of the first onset of CRC with alcohol consumption was stronger in men, carriers of pathogenic MLH1 and MSH2 mutations (vs those with pathogenic MSH6, PMS2 and EPCAM mutations), and tumors in the proximal colon cancer (vs distal colon and rectal cancer).

Conclusions

Alcohol consumption was associated with earlier onset of the first CRC in Japanese LS cohort. The association was stronger in men, carriers of pathogenic MLH1 and MSH2 mutations, and tumors located in the proximal colon. Our findings illuminate the mechanism of LS-associated carcinogenesis and serve as a recommendation for discontinuing or ceasing alcohol consumption.

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Acknowledgements

Kenta Murotani, Ph.D., Professor, Biostatistics Center, Kurume University, contributed to the statistical analyses and their interpretation. We thank Edanz Group (https://www.jp.edanz.com/ac) for editing a draft of this manuscript.

Author information

Authors and Affiliations

  1. Department of Surgery, Kurume University, 67 Asahi-machi, Kurume, Fukuoka, 830-0037, Japan

    Kenji Fujiyoshi, Tomoya Sudo & Fumihiko Fujita

  2. The Committee of Hereditary Colorectal Cancer of the Japanese Society for Cancer of the Colon and Rectum, Tokyo, Japan

    Tomoya Sudo, Akiko Chino, Kiwamu Akagi, Akinari Takao, Masayoshi Yamada, Kohji Tanakaya, Hideyuki Ishida, Koji Komori, Soichiro Ishihara, Masashi Miguchi, Keiji Hirata, Yasuyuki Miyakura, Toshiaki Ishikawa, Tatsuro Yamaguchi & Naohiro Tomita

  3. Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan

    Akiko Chino

  4. Department of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan

    Kiwamu Akagi

  5. Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Akinari Takao & Tatsuro Yamaguchi

  6. Department of Endoscopy, Gastrointestinal Endoscopy Division, National Cancer Center, Tokyo, Japan

    Masayoshi Yamada

  7. Department of Surgery, Iwakuni Clinical Center, Iwakuni, Japan

    Kohji Tanakaya

  8. Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan

    Hideyuki Ishida

  9. Department of Gastroenterological Surgery, Aichi Cancer Center, Aichi, Japan

    Koji Komori

  10. Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Soichiro Ishihara

  11. Department of Gastroenterological Surgery, Hiroshima Prefectural Hospital, Hiroshima, Japan

    Masashi Miguchi

  12. Department of Surgery I, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan

    Keiji Hirata

  13. Department of Surgery, Saitama Medical Center Jichi Medical University, Saitama, Japan

    Yasuyuki Miyakura

  14. Tokyo Medical and Dental University, Tokyo, Japan

    Toshiaki Ishikawa & Kenichi Sugihara

  15. Cancer Treatment Center, Toyonaka Municipal Hospital, Toyonaka, Japan

    Naohiro Tomita

  16. The Japanese Society for Cancer of the Colon and Rectum, Tokyo, Japan

    Yoichi Ajioka & Kenichi Sugihara

  17. Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan

    Yoichi Ajioka

Authors
  1. Kenji Fujiyoshi
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  2. Tomoya Sudo
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  19. Kenichi Sugihara
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Contributions

All authors contributed to review and revision. KF, TS, and FF: developed the main concept and designed the study. KF and TS: responsible for collection of data, including medical information and surgical and histopathological characteristics. KF and TS: performed data analysis and interpretation. KF: drafted the manuscript. KF, TS, FF, AC, KA, AT, MY, KT, HI, KK, SI, MM, KH, YM, TI, NT, YA, and KS: contributed to editing and critical revision of important intellectual content.

Corresponding author

Correspondence to Kenji Fujiyoshi.

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Fujiyoshi, K., Sudo, T., Fujita, F. et al. Risk of first onset of colorectal cancer associated with alcohol consumption in Lynch syndrome: a multicenter cohort study. Int J Clin Oncol 27, 1051–1059 (2022). https://doi.org/10.1007/s10147-022-02148-2

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  • DOI: https://doi.org/10.1007/s10147-022-02148-2

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