Familial gastric cancer, in which more than one person in a family has gastric cancer, includes hereditary diffuse gastric cancer, gastric adenocarcinoma and proximal gastric polyposis, and familial intestinal gastric cancer. Familial gastric cancer is usually referred to hereditary diffuse gastric cancer. In the following, we will introduce how to prevent familial gastric cancer in the context of hereditary diffuse gastric cancer.
Who needs to take steps to prevent familial gastric cancer?
Hereditary diffuse gastric cancer is primarily caused by mutations in the CDH1 gene, and in recent years some investigators have also reported an association with mutations in the CTNNA1 gene. However, only about 40% of patients with hereditary diffuse gastric cancer can be detected with the mutation.
People with CDH1 gene mutations, regardless of gender, have more than an 80% chance of developing hereditary diffuse gastric cancer at age 80, and women with CDH1 gene mutations also have a 60% chance of developing lobular breast cancer. Therefore, people with CDH1 mutations should take steps to prevent familial gastric cancer.
How to prevent it?
How to prevent it?
Once a family with hereditary diffuse gastric cancer is identified, genetic counseling and genetic testing are particularly important. Currently, only families who meet the criteria for hereditary diffuse gastric cancer established by the International Hereditary Gastric Cancer Collaborative Group are allowed to have CDH1 genetic testing. For those who test positive for the CDH1 gene, common means of prevention include prophylactic total gastric resection and endoscopy.
Preventive total gastrectomy is the only effective means of preventing hereditary diffuse gastric cancer in CDH1 gene mutation carriers. Preventive total gastrectomy is usually recommended for CDH1 gene mutation carriers aged 18 to 40 years before they develop symptoms of hereditary diffuse gastric cancer. Prophylactic gastrectomy is not recommended earlier than 18 years of age, but should be considered when a family member has been diagnosed with gastric cancer earlier than 25 years of age. Prior to surgery, a detailed consultation with a multidisciplinary team including a gastroenterologist, surgeon, nutritionist, genetic counselor, and nurse specialist is required. After evaluation, if prophylactic total gastrectomy is found to be unsuitable, regular annual endoscopic surveillance as well as tissue biopsy should generally be performed. In addition, because women with CDH1 gene mutations are at risk for lobular breast cancer, annual mammograms (X-rays) and magnetic resonance imaging (MRI) are usually required.
The primary prevention for gastric adenocarcinoma and proximal gastric polyposis is endoscopic surveillance and eventually prophylactic total gastrectomy; all first-degree relatives (parents, siblings, and children) should have regular esophagogastroduodenoscopy and colonoscopy. As for familial intestinal-type gastric cancer, there are not many preventive tools available.
While genetic counseling and genetic testing are promising, only families who meet the criteria for hereditary diffuse gastric cancer developed by the International Hereditary Gastric Cancer Collaborative Group are currently allowed to have CDH1 genetic testing, and detection rates are usually not high. Specific mutated genes for gastric adenocarcinoma and proximal gastric polyposis, and familial intestinal gastric cancer still need to be discovered, and the technical means of genetic testing also need to be further improved. At this stage, for the diagnosis and prevention of familial gastric cancer, attention to family history, appropriate prophylactic total gastric resection, and endoscopic surveillance may be a more reliable approach.