HDGC is the most common genetic predisposing syndrome for gastric cancer, with germline truncating mutations of the E-cadherin gene (CDH1) detected in 30%-50% of diffuse-type gastric cancers. According to National Comprehensive Cancer Network (NCCN) guidelines, families that harbor these mutations have an autosomal dominant pattern of inheritance with a very high penetrance. Prophylactic gastrectomy (without a D2 lymph node dissection) between the ages of 18 and 40 years for asymptomatic carriers with a family history of HDGC is recommended. For individuals who decline prophylactic gastrectomy, upper endoscopy with multiple random biopsies should be offered every 6-12 months. The same guidelines also suggest that women with CDH1 mutations are at increased risk for breast cancer and should be followed similar to BRCA1/BRCA2 mutation carriers.
Lynch syndrome, also called hereditary nonpolyposis colorectal cancer, is the most common form of hereditary colorectal cancer. It is inherited as an autosomal dominant syndrome because of defective mismatch repair proteins. Although the NCCN guidelines note that gastric cancer is the second most common extracolonic cancer (after endometrial cancer) in patients with Lynch syndrome, they do not find clear evidence to support screening for gastric, duodenal, or small bowel cancer in these patients. In selected individuals of Asian descent (or from countries with a high background incidence of gastric cancer), clinicians may consider upper endoscopy with visualization of the duodenum at the time of colonoscopy every 3-5 years, beginning at age 30-35 years. Testing for Helicobacter pylori, and treatment if it is found, may also be considered.
Familial adenomatous polyposis is the most common adenomatous polyposis syndrome. It is an autosomal dominant inherited disorder characterized by the early onset of hundreds to thousands of adenomatous polyps throughout the colon. If left untreated, all patients with this syndrome will develop colon cancer by age 35-40 years. In addition, an increased risk exists for the development of other malignancies. The NCCN guidelines recommend examining the stomach at the time of duodenoscopy. Special screening or surgery should only be considered for fundic gland polyps with high-grade dysplasia. Nonfundic gland polyps should be managed endoscopically; polyps with high-grade dysplasia that cannot be removed or invasive cancer detected on biopsy should be referred for gastrectomy.
Peutz-Jeghers syndrome is an autosomal dominant inherited disorder characterized by intestinal hamartomatous polyps in association with a distinct pattern of skin and mucosal macular melanin deposition. Patients with Peutz-Jeghers syndrome have an estimated 15- to 18-fold increased risk of developing intestinal cancer compared with the general population. NCCN guidelines recommend that esophagogastroduodenoscopy surveillance should be considered. Screening should begin in late teens and repeat every 2-3 years.
Learn more about hereditary cancer predisposition syndromes.
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Cite this: Elwyn C. Cabebe. Fast Five Quiz: Advanced and Metastatic Gastric Cancer - Medscape - Apr 06, 2022.