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Clin Gastroenterol Hepatol. 2019 Jul 15. pii: S1542-3565(19)30745-1. doi: 10.1016/j.cgh.2019.07.012. [Epub ahead of print]

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

Author information

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.
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: Matthew_Yurgelun@dfci.harvard.edu.

Abstract

BACKGROUND & AIMS:

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.

METHODS:

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).

RESULTS:

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 first-degree relative 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 among carriers of pathogenic mutations.

CONCLUSIONS:

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 with having a first-degree relative 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.

KEYWORDS:

Familial; HNPCC; Screening; Stomach

PMID:
31319185
DOI:
10.1016/j.cgh.2019.07.012

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