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Clinical Factors Associated With Gastric Cancer in Individuals With Lynch Syndrome.

Authors
  • Kim, Jaihwan1
  • Braun, Danielle2
  • Ukaegbu, Chinedu3
  • Dhingra, Tara G3
  • Kastrinos, Fay4
  • Parmigiani, Giovanni2
  • Syngal, Sapna5
  • Yurgelun, Matthew B6
  • 1 Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. , (North Korea)
  • 2 Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
  • 3 Division of Population Sciences, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • 4 Herbert Irving Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York.
  • 5 Division of Population Sciences, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
  • 6 Division of Population Sciences, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: [email protected]
Type
Published Article
Journal
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
Publication Date
Apr 01, 2020
Volume
18
Issue
4
Identifiers
DOI: 10.1016/j.cgh.2019.07.012
PMID: 31319185
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Lynch syndrome is the most common inherited cause of gastrointestinal cancer and increases risk for a variety of malignancies, including gastric cancer. We aimed to identify clinical factors associated with gastric cancer in carriers of germline variants causing Lynch syndrome. We collected data from 52,758 consecutive individuals tested for genetic variants associated with Lynch syndrome from June 2006 through July 2013 at a commercial laboratory. We obtained clinical and demographic data, as well as information on personal and family histories of cancer (first- and second-degree relatives) from forms completed by ordering providers. We performed multivariate logistic regression to identify clinical factors associated with gastric cancer in carriers of mutations that cause Lynch syndrome (pathogenic mutations). After we excluded individuals with missing clinical data (n = 1664) or with multiple pathogenic mutations (n = 8), we analyzed data from 51,086 individuals. Of these, 3828 persons carried pathogenic mutations (1346 with mutations in MLH1, 1639 with mutations in MSH2, 670 with mutations in MSH6, 145 with mutations in PMS2, and 28 with mutations in EPCAM). Of the 3828 carriers of pathogenic mutations, 41 (1.1%) had a previous gastric cancer and 350 (9.1%) had 1 or more first- or second-degree relatives with gastric cancer. In multivariate analysis, male sex (odds ratio [OR], 2.82; 95% CI, 1.48-5.38), older age (OR, 2.07 per 10 years; 95% CI, 1.64-2.61), mutations in MLH1 (OR, 6.53; 95% CI, 1.50-28.42) or MSH2 (OR, 5.23 compared to mutations in MSH6, PMS2, or EPCAM; 95% CI, 1.21-22.71), and number of first-degree relatives with gastric cancer (OR, 2.52; 95% CI, 1.42-4.45), but not second-degree relatives (OR, 1.12; 95% CI, 0.40-3.18) were independently associated with gastric cancer among carriers of pathogenic mutations. In an analysis of data from almost 4000 carriers of Lynch syndrome-associated mutations, we found history of gastric cancer to be independently associated with male sex, older age, mutations in MLH1 or MSH2, and number of first-degree relatives with gastric cancer. These findings suggest that personalized, risk-stratified approaches to gastric cancer surveillance may be appropriate for individuals with Lynch syndrome-associated mutations. Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.

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