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Presymptomatic identification of CDH1 germline mutation in a healthy korean individual with family history of gastric cancer.

Choi HJ, Ki CS, Suh SP, Kim JW - Ann Lab Med (2014)

Bottom Line: Screening for the GC-causing CDH1 mutation may provide valuable information for genetic counseling, testing, and risk-reduction management for the as-yet unaffected family members.Eventually, c.1018A>G in CDH1, a known disease-causing mutation, was found.To our knowledge, this is the first Korean case of presymptomatic detection of CDH1 mutation, and it highlights the importance of genetic screening for individuals with a family history of GC, especially in high-risk geographical areas.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hospital, Gwanju, Korea.

ABSTRACT
Gastric cancer (GC) is one of the most common cancers with high morbidity and mortality. Familial GC is seen in 10% of cases, and approximately 3% of familial GC cases arise owing to hereditary diffuse gastric cancer (HDGC). CDH1, which encodes the protein E-cadherin, is the only gene whose mutations are associated with HDGC. Screening for the familial GC-predisposing gene has been neglected in high-risk countries such as Korea, China, and Japan, where all the cases have been attributed to Helicobacter pylori or other carcinogens. Screening for the GC-causing CDH1 mutation may provide valuable information for genetic counseling, testing, and risk-reduction management for the as-yet unaffected family members. An asymptomatic 44-yr-old Korean male visited our genetic clinic for consultation owing to his family history of GC. Eventually, c.1018A>G in CDH1, a known disease-causing mutation, was found. As of the publication time, the individual is alive without the evidence of GC, and is on surveillance. To our knowledge, this is the first Korean case of presymptomatic detection of CDH1 mutation, and it highlights the importance of genetic screening for individuals with a family history of GC, especially in high-risk geographical areas.

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Related in: MedlinePlus

Pedigree of the individual's family in our case. Solid symbol represents the individual with tumor(s). Types of tumors are indicated, along with ages (yr) at the time of diagnosis and death (if applicable). An asterisk (*) marks the examined individual found to carry the germline CDH1 mutation. Arrow indicates this case.Abbreviations: Dx, diagnosis; d, death; Ca, cancer.
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Figure 1: Pedigree of the individual's family in our case. Solid symbol represents the individual with tumor(s). Types of tumors are indicated, along with ages (yr) at the time of diagnosis and death (if applicable). An asterisk (*) marks the examined individual found to carry the germline CDH1 mutation. Arrow indicates this case.Abbreviations: Dx, diagnosis; d, death; Ca, cancer.

Mentions: To our knowledge, this is the first report on presymptomatic identification of CDH1 mutation in a Korean individual with a family history of diffuse GC (DGC). Being exposed to medical information on genetic mutations associated with GC through a newspaper article, a 44-yr-old male visited our genetic counseling clinic for genetic testing of the gene associated with GC. He showed no specific symptoms or anomalous findings on physical examination, as well as no known history of other genetic disorders. His father died of GC at the age of 54; and a year after GC diagnosis at the age of 52, one of his paternal aunts showed terminal-stage GC (Fig. 1). However, histological diagnosis was not known or performed for his father and aunt. To be diagnosed with HDGC, a family should meet the criteria proposed by the International Gastric Cancer Linkage Consortium (IGCLC) [7], which includes the followings: 1) two or more documented cases of DGC in first- or second-degree relatives, with at least one case diagnosed before the age of 50 yr; or 2) three or more cases of documented DGC in first- or second-degree relatives, independent of their ages. Previously, 25-50% of the families fulfilling the criteria for HDGC were shown to have germline mutations in CDH1 [7, 8]. Considering the family history, genetic analysis of the CDH1 was performed with the patient's written informed consent; the analysis did not fulfill the clinical criteria of HDGC as defined by the IGCLC.


Presymptomatic identification of CDH1 germline mutation in a healthy korean individual with family history of gastric cancer.

Choi HJ, Ki CS, Suh SP, Kim JW - Ann Lab Med (2014)

Pedigree of the individual's family in our case. Solid symbol represents the individual with tumor(s). Types of tumors are indicated, along with ages (yr) at the time of diagnosis and death (if applicable). An asterisk (*) marks the examined individual found to carry the germline CDH1 mutation. Arrow indicates this case.Abbreviations: Dx, diagnosis; d, death; Ca, cancer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4151009&req=5

Figure 1: Pedigree of the individual's family in our case. Solid symbol represents the individual with tumor(s). Types of tumors are indicated, along with ages (yr) at the time of diagnosis and death (if applicable). An asterisk (*) marks the examined individual found to carry the germline CDH1 mutation. Arrow indicates this case.Abbreviations: Dx, diagnosis; d, death; Ca, cancer.
Mentions: To our knowledge, this is the first report on presymptomatic identification of CDH1 mutation in a Korean individual with a family history of diffuse GC (DGC). Being exposed to medical information on genetic mutations associated with GC through a newspaper article, a 44-yr-old male visited our genetic counseling clinic for genetic testing of the gene associated with GC. He showed no specific symptoms or anomalous findings on physical examination, as well as no known history of other genetic disorders. His father died of GC at the age of 54; and a year after GC diagnosis at the age of 52, one of his paternal aunts showed terminal-stage GC (Fig. 1). However, histological diagnosis was not known or performed for his father and aunt. To be diagnosed with HDGC, a family should meet the criteria proposed by the International Gastric Cancer Linkage Consortium (IGCLC) [7], which includes the followings: 1) two or more documented cases of DGC in first- or second-degree relatives, with at least one case diagnosed before the age of 50 yr; or 2) three or more cases of documented DGC in first- or second-degree relatives, independent of their ages. Previously, 25-50% of the families fulfilling the criteria for HDGC were shown to have germline mutations in CDH1 [7, 8]. Considering the family history, genetic analysis of the CDH1 was performed with the patient's written informed consent; the analysis did not fulfill the clinical criteria of HDGC as defined by the IGCLC.

Bottom Line: Screening for the GC-causing CDH1 mutation may provide valuable information for genetic counseling, testing, and risk-reduction management for the as-yet unaffected family members.Eventually, c.1018A>G in CDH1, a known disease-causing mutation, was found.To our knowledge, this is the first Korean case of presymptomatic detection of CDH1 mutation, and it highlights the importance of genetic screening for individuals with a family history of GC, especially in high-risk geographical areas.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hospital, Gwanju, Korea.

ABSTRACT
Gastric cancer (GC) is one of the most common cancers with high morbidity and mortality. Familial GC is seen in 10% of cases, and approximately 3% of familial GC cases arise owing to hereditary diffuse gastric cancer (HDGC). CDH1, which encodes the protein E-cadherin, is the only gene whose mutations are associated with HDGC. Screening for the familial GC-predisposing gene has been neglected in high-risk countries such as Korea, China, and Japan, where all the cases have been attributed to Helicobacter pylori or other carcinogens. Screening for the GC-causing CDH1 mutation may provide valuable information for genetic counseling, testing, and risk-reduction management for the as-yet unaffected family members. An asymptomatic 44-yr-old Korean male visited our genetic clinic for consultation owing to his family history of GC. Eventually, c.1018A>G in CDH1, a known disease-causing mutation, was found. As of the publication time, the individual is alive without the evidence of GC, and is on surveillance. To our knowledge, this is the first Korean case of presymptomatic detection of CDH1 mutation, and it highlights the importance of genetic screening for individuals with a family history of GC, especially in high-risk geographical areas.

Show MeSH
Related in: MedlinePlus