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Penetrance of Gastric Adenocarcinoma Susceptibility Genes: A Systematic Review

Annals of Surgical Oncology volume 30, pages 1795–1807 (2023)Cite this article

Abstract

Background

Gastric adenocarcinoma (GAC) is the fifth most common cancer in the world, and the presence of germline pathogenic variants has been linked with approximately 5% of gastric cancer diagnoses. Multiple GAC susceptibility genes have been identified, but information regarding the risk associated with pathogenic variants in these genes remains obscure. We conducted a systematic review of existing studies reporting the penetrance of GAC susceptibility genes.

Methods

A structured search query was devised to identify GAC-related papers indexed in MEDLINE/PubMed. A semi-automated natural language processing algorithm was applied to identify penetrance papers for inclusion. Original studies reporting the penetrance of GAC were included and the full-text articles were independently reviewed. Summary statistics, effect estimates, and precision parameters from these studies were compiled into a table using a predetermined format to ensure consistency.

Results

Forty-five studies were identified reporting the penetrance of GAC among patients harboring mutations in 13 different genes: APC, ATM, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, PMS2, MUTYH-Monoallelic, NBN, and STK11.

Conclusion

Our systematic review highlights the importance of testing for germline pathogenic variants in patients before the development of GAC. Management of patients who harbor a pathogenic mutation is multifactorial, and clinicians should consider cancer risk for each applicable gene–cancer association throughout the screening and management process. The scarcity of studies we found investigating the risk of GAC among patients with pathogenic variants in GAC susceptibility genes highlights the need for more investigations that focus on producing robust risk estimates for gene–cancer associations.

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Fig. 1

Availability of Data, Code, and Other Materials

The NLP code used in this review has been made publicly available online at https://github.com/YujiaBao/PubmedClassifier. Annotated data can be made available to researchers who wish to collaborate on expanding the cancer gene knowledge base. Please contact the corresponding author, Kevin S. Hughes, MD, FACS, for more information.

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Acknowledgment

The authors wish to acknowledge their colleague, Dr. Mark Robson, who provided expertise that greatly assisted the research and construction of this manuscript.

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  1. Sahar Hosseini and Ahmet Acar contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Sahar Hosseini MD

  2. Department of Emergency, Avrupa Hospital, Istanbul, Turkey

    Ahmet Acar MD

  3. College of Medicine, American University of Antigua, Coolidge, Antigua, Antigua and Barbuda

    Meghdeep Sen BS

  4. Division of Oncologic and Endocrine Surgery, Department of Surgery, Medical University of South Carolina, Charleston, SC, USA

    Kiersten Meeder MPH, Jeffrey M. Sutton MD, FACS, FSSO & Kevin Hughes MD, FACS

  5. Department of Surgery, Montefiore Medical Center, Bronx, NY, USA

    Preeti Singh MD

  6. Department of Surgery, Washington University School of Medicine, St Louis, MO, USA

    Kanhua Yin MD, MPH

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Disclosure

Kevin Hughes receives honoraria from Hologic (surgical implant for radiation planning with breast conservation and wire-free breast biopsy), TME (Targeted Medical Education, genetics education and consulting), MedNeon (genetics education company), and Myriad Genetics. He also has a financial interest in CRA Health (formerly Hughes RiskApps), which was recently acquired by Volpara; CRA Health develops risk assessment models/software with a particular focus on breast cancer and colorectal cancer, and Kevin Hughes is a founder of the company. He is also the Co-Creator of Ask2Me.Org, which is freely available for clinical use and is licensed for commercial use by the Dana Farber Cancer Institute and the Massachusetts General Hospital (MGH). His interests in CRA Health and Ask2Me.Org were reviewed and are managed by MGH and Partners Health Care in accordance with their conflict of interest policies. Sahar Hosseini, Ahmet Acar, Meghdeep Sen, Kiersten Meeder, Preeti Singh, Kanhua Yin, and Jeffrey M. Sutton declare that they have no conflicts of interest.

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Hosseini, S., Acar, A., Sen, M. et al. Penetrance of Gastric Adenocarcinoma Susceptibility Genes: A Systematic Review. Ann Surg Oncol 30, 1795–1807 (2023). https://doi.org/10.1245/s10434-022-12829-x

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