Journal
CANCER
Volume 112, Issue 12, Pages 2655-2663Publisher
JOHN WILEY & SONS INC
DOI: 10.1002/cncr.23501
Keywords
diffuse gastric cancer; family pedigree; hereditary; prophylactic total gastrectomy; type E-cadherin (epithelial) gene
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Funding
- NCI NIH HHS [1U01 CA 86389, U01 CA086389, U01 CA086389-09] Funding Source: Medline
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BACKGROUND. A subset of patients with diffuse gastric cancer harbor deleterious cancer-causing germline mutations in the type 1 E-cadherin (epithelial) gene (CDHI), which predisposes to the autosomal dominantly inherited hereditary diffuse gastric cancer (HDGC) syndrome. These mutations are associated with a 70% life-time risk for diffuse gastric cancer (DGC) and an additional 40% risk for lobular breast cancer in women. Management options for unaffected mutation carriers include prophylactic total gastrectomy. METHODS. Four HDGC pedigrees from a cohort of 56 CDHI mutation- positive families were subjected to further analysis. Cancer diagnoses, whenever possible, were verified with pathology reports and/or slides/tissue block review. Genetic counseling for family members covered the natural history of HDGC, the pros and cons of mutation testing, the lack of effective screening procedures available to CDHI mutation- positive individuals, and the option for them of prophylactic total gastrectomy. RESULTS. Within the 4 families, carrier testing for mutations in the CDHI gene was carried out on 52 individuals, including 25 individuals who were positive for mutation. Prophylactic gastrectomies were performed on a total of 17 individuals from 3 of the families, including 11 first cousins from 1 of the families. Occult DGC was diagnosed in gastrectomy specimens from 13 of 17 individuals (76.5%). During follow-up questioning, each of the 11 cousins stated that the decision for the prophylactic procedure was the right one for them. CONCLUSIONS. Unaffected mutation carriers from HDGC families face difficult decisions and can be assisted best through education and interactions with counseling by an informed multidisciplinary team.
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