| 18 19 | See page 67 for references Potential management options Management guidelines for BRIP1 mutations are evolving. A thorough family history review is important to better understand cancer risks and to develop an individualized management plan. For women with BRIP1 mutations, NCCN recommends the following: · ·A discussion about risk-reducing salpingo-oophorectomy at approximately age 45-50 years or earlier if early onset ovarian cancer is present in the family history. · ·Note: The optimal age at which to perform this procedure is unknown; however, initial studies of families with BRIP1 mutations suggest most ovarian cancer diagnoses occur after age 50. There are currently no screening or management recommendations for other possible types of cancer associated with BRIP1 mutations, and potential management for those cancers is often individualized based on family history. In rare instances an individual may inherit two mutations in BRIP1, one from each parent. This has the potential to result in a rare condition called Fanconi anemia. For individuals who test positive for BRIP1, it may be appropriate to consider carrier screening for BRIP1 mutations in their spouse/partner. CDH1 gene summary Hereditary diffuse gastric cancer Gene name CDH1 Associated syndrome Hereditary diffuse gastric cancer (HDGC) Primary associated cancers Diffuse gastric cancer, lobular breast cancer Frequency Rare; unknown Inheritance pattern Autosomal dominant Overview · ·Although the incidence of gastric cancer is highest in Japan and China, most CDH1 mutations are found in European populations. · ·An estimated 1%–3% of cases of gastric cancer are caused by hereditary diffuse gastric cancer. · ·The average age at diagnosis of cancer for affected individuals is 38 years. · ·30%–50% of those with clinically diagnosed hereditary diffuse gastric cancer will have an identifiable gene mutation. About hereditary diffuse gastric cancer HDGC is a hereditary cancer syndrome that increases an individual’s risk of developing diffuse gastric cancer. HDGC leads to a cancer called diffuse-type, signet ring cell gastric adenocarcinoma. The signet ring cells appear as isolated cells or in small clusters in the lining of the stomach and are not easily visualized on upper endoscopy screening. For this reason, most cases of diffuse gastric cancer are diagnosed at late stages (III or IV), when the cancer is more difficult to treat. HDGC syndrome also causes increased risk for lobular breast cancer in women.