Gastric cancer is the fourth most common malignancy worldwide and the second leading cause of death in oncology. In terms of classification, there are different types, the risk factors for which are diverse and unlock the disease in its complexity. In 20% of cases of stomach cancer, it is a diffuse variant of the oncological disease. This means that the process is not limited to a certain area of ​​the organ, but covers a significantly larger area (diffuse). For all oncological diseases, it has already been proven that complex risk factors lead to genetic changes causing malignant transformation of cells. In cases of hereditary diffuse gastric cancer, however, the only and sufficient reason for the development of the disease is inherited or acquired mutations in certain gene loci (in half of the patients in the testable CDH1 gene). Carriers of mutations in the CDH1 gene account for 30% to 50% of cases of hereditary diffuse gastric cancer. More than 50 mutations in this gene have been identified, the final effect of which is the development of an oncological disease in more than 80% of the carriers followed (incomplete but high penetrance=expression of the gene). Statistics show that the same carriers developed a second primary cancer – of the breast in 39% of cases. Mutations in CDH1 are an example of genetic changes in a single gene, the change in which is responsible for the development of two different tumors. Either localization can develop before the other, as well as simultaneously. Scientific proof of the association of mutations in the CDH1 gene with the development of hereditary diffuse gastric cancer and lobular breast cancer has practical value. Examination of first-line relatives of patients with the indicated mutations and oncological diseases can define healthy individuals who are at real and high risk of developing cancer. Recommendations for genetic screening of relatives of cancer patients with CDH1 mutations are: Families with one or more cases of diffuse gastric cancer; Patients with diffuse gastric cancer without a family history, but developed the disease before the age of 40; Patients with two metachronous tumors – diffuse gastric cancer and lobular breast cancer. The presence of CDH1 mutations in healthy relatives requires familiarizing these people with the risks of developing malignant tumors. The most effective prophylactic method in these cases is radical surgery – removal of the stomach (gastrectomy). When gastrectomy is refused, control prophylactic studies for follow-up and early diagnosis have not proven to be more effective in sufficiently early detection of diffuse gastric cancer. NEWS_MORE_BOX In cases of active surveillance, a twice-yearly gastroscopy with at least 6 biopsies from the different anatomical parts of the stomach or suspicious areas is required. Active follow-up should begin at least 10 years before the diagnosis of the disease in the affected relative.Given the 39% risk of lobular breast cancer, CDH1 mutation carriers (healthy and diseased) are recommended to have yearly mammography and breast MRI after age 35. Prophylactic removal of the stomach or most of it in carriers of CDH1 mutations significantly reduces and even eliminates the risk of diffuse gastric cancer, but to a large extent worsens the quality of life of these people. Complications with a high rate are diarrhea, malabsorption syndrome, weight reduction, anemia. Despite the complications, performing a gastrectomy in these cases is a potentially life-saving intervention. The 5-year survival rate of patients with diffuse gastric carcinoma is 10%. The final decision is made jointly by the healthy mutation carrier and a multidisciplinary team of specialists – medical oncologists, geneticists, surgeons, gastroenterologists and molecular biologists.