Hereditary diffuse gastric cancer

Diagnosis, genetic counseling, and prophylactic total gastrectomy

Henry T. Lynch, Pardeep Kaurah, Debrah Wirtzfeld, Wendy S. Rubinstein, Scott Weissman, Jane F. Lynch, William Grady, Sara Wiyrick, Janine Senz, David G. Huntsman

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2655-2663
Number of pages9
JournalCancer
Volume112
Issue number12
DOIs
StatePublished - Jun 15 2008

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Genetic Counseling
Gastrectomy
Stomach Neoplasms
Mutation
Germ-Line Mutation
Cadherins
Pedigree
Natural History
Genes
Counseling
Neoplasms
Pathology
Breast Neoplasms
Education

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Lynch, H. T., Kaurah, P., Wirtzfeld, D., Rubinstein, W. S., Weissman, S., Lynch, J. F., ... Huntsman, D. G. (2008). Hereditary diffuse gastric cancer: Diagnosis, genetic counseling, and prophylactic total gastrectomy. Cancer, 112(12), 2655-2663. https://doi.org/10.1002/cncr.23501

Hereditary diffuse gastric cancer : Diagnosis, genetic counseling, and prophylactic total gastrectomy. / Lynch, Henry T.; Kaurah, Pardeep; Wirtzfeld, Debrah; Rubinstein, Wendy S.; Weissman, Scott; Lynch, Jane F.; Grady, William; Wiyrick, Sara; Senz, Janine; Huntsman, David G.

In: Cancer, Vol. 112, No. 12, 15.06.2008, p. 2655-2663.

Research output: Contribution to journalArticle

Lynch, HT, Kaurah, P, Wirtzfeld, D, Rubinstein, WS, Weissman, S, Lynch, JF, Grady, W, Wiyrick, S, Senz, J & Huntsman, DG 2008, 'Hereditary diffuse gastric cancer: Diagnosis, genetic counseling, and prophylactic total gastrectomy', Cancer, vol. 112, no. 12, pp. 2655-2663. https://doi.org/10.1002/cncr.23501
Lynch HT, Kaurah P, Wirtzfeld D, Rubinstein WS, Weissman S, Lynch JF et al. Hereditary diffuse gastric cancer: Diagnosis, genetic counseling, and prophylactic total gastrectomy. Cancer. 2008 Jun 15;112(12):2655-2663. https://doi.org/10.1002/cncr.23501
Lynch, Henry T. ; Kaurah, Pardeep ; Wirtzfeld, Debrah ; Rubinstein, Wendy S. ; Weissman, Scott ; Lynch, Jane F. ; Grady, William ; Wiyrick, Sara ; Senz, Janine ; Huntsman, David G. / Hereditary diffuse gastric cancer : Diagnosis, genetic counseling, and prophylactic total gastrectomy. In: Cancer. 2008 ; Vol. 112, No. 12. pp. 2655-2663.
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AU - Rubinstein, Wendy S.

AU - Weissman, Scott

AU - Lynch, Jane F.

AU - Grady, William

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N2 - 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.

AB - 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.

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