Abstract:
BACKGROUND:A subset of patients with diffuse gastric cancer harbor deleterious cancer-causing germline mutations in the type 1 E-cadherin (epithelial) gene (CDH1), 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 CDH1 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 CDH1 mutation-positive individuals, and the option for them of prophylactic total gastrectomy. RESULTS:Within the 4 families, carrier testing for mutations in the CDH1 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.
journal_name
Cancerjournal_title
Cancerauthors
Lynch HT,Kaurah P,Wirtzfeld D,Rubinstein WS,Weissman S,Lynch JF,Grady W,Wiyrick S,Senz J,Huntsman DGdoi
10.1002/cncr.23501subject
Has Abstractpub_date
2008-06-15 00:00:00pages
2655-63issue
12eissn
0008-543Xissn
1097-0142journal_volume
112pub_type
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