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

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.

Keywords: Asymptomatic; CDH1; Hereditary; Neoplasms; Stomach.

Fig. 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.

Fig. 2

Sequence analysis of CDH1. Direct sequencing showed that he and his older brother he were heterozygous for a c.1018A>G mutation in exon 8, leading to the amino acid substitution from threonine to alanine.