Prevention of gastric cancer in families with gastric oncogene E-cadherin

Posted by Master, Doctor Mai Vien Phuong - Department of Examination & Internal Medicine - Vinmec Central Park International General Hospital

Stomach cancer is a multifactorial cancer that is numbered among its causes, both environmental and genetic. It is mainly diagnosed in South America and Southeast Asia, where it shows the highest probability rates, and it is diagnosed relatively rarely in Western and North American countries.

Although the molecular mechanisms leading to gastric cancer development are only partially known, three main causes have been well characterized: Helicobacter pylori (H. pylori) infection, a diet rich in foods salt and/or smoked and red meat, and epithelial cadherin factor (E-cadherin gene) mutations. Unhealthy diet and H. pylori infection may induce genotypic and phenotypic variation of gastric cancer cells, but their effects may be influenced by a diet rich in vegetables and fresh fruit. Many authors have recently focused their attention on the importance of a well-balanced diet, recommending a necessary eating education starting in childhood.
Continuous monitoring is needed in carriers of the mutated E-cadherin gene, as they are more likely to develop stomach cancer, also in the inner layers of the stomach. Above all in the United States, some carriers decide to have gastric bypass surgery, preferring lifestyle changes rather than living with the awareness of the development of stomach cancer. This type of choice is purely personal and therefore cannot be made in clinical management.

Environmental and genetic causes may be involved and an important role in reducing the incidence of gastric carcinoma can be mentioned for prevention. Diets high in salted and smoked foods, such as Helicobacter pylori (H. pylori) infection, are the best known environmental causes, while loss of epithelial cadherin (E-cadherin) and Run-related transcription factor 3 (RUNX3) expression is often a genetic marker of gastric cancer.

Therefore, prevention can be viewed from different points of view. General improvements in lifestyle, including a diet rich in vegetables and a reduction in red meat and alcohol intake, may be helpful in preventing gastric cancer, but more specific strategies must be applied depending on the environment and background. genetic background of different people. In some cases, such as in E-cadherin mutation-carrying families, prevention may be more important than scheduled endoscopy and, at times, prophylactic gastrectomy may be the appropriate option. unify.

Prevention of stomach cancer must be done in two different directions: Eliminate and reconcile the possible causes. Consider dietary habits, a powerful strategy demonstrated by replacing processed foods with fresh foods, taking care to include more vegetables in the body. Adopting a healthy diet is an effective approach to preventing stomach tumors in people with or without H. pylori infection. However, in this last case, an appropriate eradication therapy must be established and a well-scheduled follow-up visit must be performed. Here we will discuss all these different aspects in detail, along with a strategy for the prevention of gastric cancer caused by E-cadherin mutations.

E-cadherin, also known as Cadherin type 1 (CDH1), is a cell adhesion glycoprotein first characterized in human cell lines by Shimoyama et al. Its role in gastric cancer development was first identified by Guilford et al., who identified a G → T nucleotide substitution in the donor consensus binding sequence of exon 7 in the Maori. This mutation produces a truncated protein that ultimately results in decreased production of E-cadherin. The examined family shows that early onset of gastric cancer is characterized by a diffuse pattern, as the other two families describe carriers of a frameshift mutation in exon 15 and an early stop codon in exon 13, respectively. With success, other authors have identified other E-cadherin mutations in different families worldwide.

All of these germline mutations are dominantly inherited, stemming from so-called Hereditary gastric cancer (HDGC), a familial dominant cancer syndrome. Updated criteria established by the International Consortium of Gastric Cancer Linkage specify that HDGC syndrome must be characterized by histological confirmation of the criteria for gastric dissemination to only one family member, includes people with diffuse gastric cancer before age 40 years with no family history including individuals and families with a diagnosis of both diffuse stomach cancer (including a person before age 50) and breast cancer. People who belong to families that also have only one of these traits should undergo genetic testing to investigate whether CDH1 is mutated. Although among familial gastric cases only 1%-3% are CDH1 mutation carriers, positive results should be followed by well-scheduled endoscopy to monitor the first cancerous lesions. . However, the effectiveness of this strategy may be nullified in cases where there are small foci, or in the mucosa. In the scientific literature, total gastrectomy is often performed as a prophylactic strategy, and often, it represents a therapeutic strategy, simply because small foci are frequently undetectable by technique. Endoscopic.
Conclusion
Stomach cancer is by far one of the most lethal tumors, especially in South America and Southeast Asia, where the frequency and mortality are highest. Rare cases of HDGC are caused by CDH1 mutations, and their prevention is above all based on ongoing monitoring, often after an actual mutational diagnosis. The number of hereditary non-stomach cancer among predisposing factors for both H. pylori infection and unhealthy diet includes high intake of salted and smoked foods, red meat and alcohol and reduced intake of vegetables and fresh fruit. Various studies have pointed to the molecular basis for the preventive effects induced by a healthy diet. More specifically, it has been found that cruciferous plants help inhibit H. pylori infection and subsequently its mutating power. On the other hand, tomatoes, garlic and citrus fruits can reduce N-nitrosation and induce apoptosis and cell cycle arrest at the G2/M phase, respectively. Therefore, consuming more vegetables helps to prevent and stop the phenomena caused by both salted and smoked foods and red meat, and by H. pylori infection.

Above all, future perspectives regarding gastric cancer prevention are focused on improving strategies against H. pylori and exploring the molecular mechanisms by which a healthy diet can function. Recent papers highlight the possibility of alternative targets for the management of bacterial infections and various parameters to define a truly nutritious and balanced diet. Recently, a review written by Nagini provides a fruitful summary of all these last key points, offering helpful suggestions for further research directions.
At Vinmec, gastric cancer screening is done through gastric endoscopy with NBI (Narrow Banding Imaging - endoscopy with narrow light band) for clearer mucosal pathological analysis results. compared with conventional endoscopy.

Besides, with the system of Laboratory Department - Vinmec International General Hospital is a synchronous testing center with a full range of fields: Biochemistry, Hematology - Blood Transfusion, Microbiology - Parasitology and Solution Pathology and 3 majors: Biochemistry, Hematology - Blood Transfusion, Microbiology - Parasitology all achieved ISO 15189:2012 certificates. Vinmec Institute of Stem Cell and Gene Technology also screened 15 common cancers in Men and 17 common cancers in Women with only one gene test.
If you have a need for consultation and examination at Vinmec Hospitals under the national health system, please book an appointment on the website for service.

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