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Harshit K. God, Zainab Mehkari, Lubna Mohammad, Moiz Javed, Aldah Altwane, Farah Ahsan, Federico Oliveri, Ian H. Rutkowski
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Cite this article: Goud HK, Mehkari Z, Mohammad L, et al. (September 12, 2020) Significance of E-cadherin gene mutations in patients with hereditary diffuse gastric cancer syndrome: a systematic review. 12(9): E10406. doi: 10.7759/.10406
Gastric cancer is the third deadliest cancer in the world. Although over the years, we have seen most of the intestinal type accounting for the highest mortality in patients, the recent increase in the diffuse form with germline E-cadherin (CDH1) mutations has added a whole new level of interest to study this association in detail. between CDH1 and diffuse gastric cancer (DGC). It introduced a set of guidelines developed by the Internal Gastric Cancer Linkage Consortium (IGCLC) for people with a family history of diffuse gastric cancer and invasive lobular breast cancer (ILBC). Analysis of this link is important to establish proper management protocols for CDH1 mutation carriers who currently involve genetic counseling, endoscopic surveillance and screening, and prophylactic total gastrectomy (PTG). The study was conducted in accordance with the “PRISMA Guidelines for Reporting Systematic Reviews and Meta-Analyses”. Peer-reviewed studies were included from the PubMed database and relevant articles were selected for inclusion in the study. Appropriate inclusion/exclusion criteria including free full-text English articles were applied while selecting articles. A total of 10 studies reviewing different study populations showed that among 42 patients diagnosed with diffuse gastric cancer, 88% were E-cadherin gene mutation positive and 100% of CDH1 mutation carriers showed microscopic changes. Signet ring cell adenocarcinoma of the stomach. The beneficial effects of PTG are greater than other treatment methods, with better survival rates and lower mortality rates. The laparoscopic approach has proven to be a safer method for gastrectomy surgery with more effective and postoperative management. The need for prophylactic mastectomy has also increased recently, thus requiring a new guideline for ILBC patients with hereditary diffuse gastric cancer (HDGC) syndrome.
Gastric cancer, an aggressive form of cancer, has one of the highest incidence and mortality rates in the world. The incidence of gastric cancer (ages 0–74) is the fifth highest in the world among both sexes, the fourth highest among men, and the eighth highest among women. Mortality is imminent, especially in advanced stages of gastric cancer, with the third highest mortality rate (ages 0–74) worldwide (third highest in men and fifth highest in women) . Gastric cancer can be classified into intestinal type and diffuse type . The overall incidence and mortality rates of sporadic and intestinal types of gastric cancer have decreased in recent years, but the diffuse type of gastric carcinoma is increasing, especially in the young age group of 20–50 years [ 2 , 3 ]. The most common type in the overall population is sporadic, intestinal-type adenocarcinoma with associated risk factors such as spicy food consumption, alcohol consumption, and the notorious Helicobacter pylori infection. On the other hand, if we study diffuse gastric cancer (usually hereditary), the incidence of which has been increasing in recent years among the young population, it takes a small proportion of the total gastric cancer in the world, but usually with fatal results. Due to the aggressive nature of the infiltration of the abdominal mucosal wall in these patients known as linitis plastica. The consequences are fatal because symptoms are presented very late in their course and then spread to the major organ systems of the body .
The overall heritability of gastric cancer is relatively low compared to all other types, ranging from 1–3%, and it is usually the diffuse type of gastric carcinoma . A close association between a cell-cell adhesion molecule, E-cadherin, and suppression by E-cadherin (CDH1) and the development of hereditary diffuse gastric carcinoma due to loss of heterozygosity was found in a New Zealand family in 1998. It has also been established that most CDH1 mutations are closely associated with family history . The establishment of the association between CDH1 and hereditary diffuse gastric cancer (HDGC) is a breakthrough that was needed for early detection of this genetic mutation in primary prevention and management. Various articles and clinical guidelines have been set for early diagnosis of tumors carrying mutations and adequate treatment protocols when CDH1 mutations are found. One article showed that about 64% of signet ring cell carcinoma (SRCC) were positive with CDH1 mutation .
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The study found another close association of CDH1 mutation and invasive lobular breast cancer (ILBC) with a 39.9% risk of breast cancer and a combined risk of diffuse gastric and ILBC development of 90% in 80-year-olds. ]. After the association of CDH1 mutations in patients with colorectal cancer and suppression of CDH1 in the pathogenesis of tumors, an opinion arose in the cancer society of a syndromic association between tumors . A criteria has been set which is revised as new data comes in but the current criteria are as follows: one case of advanced type of gastric cancer in a family with two or more cases of gastric cancer; Diagnosed with metastatic gastric cancer before the age of 40; Family or personal history of invasive lobular breast cancer and diffuse gastric cancer if at least one individual was diagnosed before the age of 50 years [8, 9]. A study evaluating the risk of CDH1 mutations in gastric and lobular breast carcinoma patients showed a risk of diffuse gastric cancer of 60–70% in men and approximately 80% in women, and a 40–50% risk of lobular breast cancer in the same study. . in women . So people who fit the above clinical criteria of hereditary diffuse gastric cancer syndrome are subjected to multiple endoscopy and biopsies and in such people CDH1 mutation is studied and in some cases prophylactic total gastrectomy (PTG) is done to stop further progression of CDH1 mutation. Cells thus improve the survival rate. In women, regular mammography screening is recommended to rule out any molecular or morphological changes in breast tissue .
This review article will discuss in detail the detailed types of hereditary gastric cancer, its genetic association, their relationship with lobular breast cancer and colorectal cancer, and the management and interventions introduced in recent years to stop this type of malignancy or its progression. Avoid completely.
The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRIMSA) guidelines for reviews and recalculations for systematic reviews and meta-analyses.
Peer-reviewed published articles were searched using the ‘PubMed’ database. The terms used to find the requested articles evaluating the significance of CDH1 (E-cadherin) mutations in hereditary diffuse gastric cancer and invasive lobular breast cancer were as follows: CDH1, E-Cadherin, gastric carcinoma, breast carcinoma, colorectal carcinoma. , signet ring cell carcinoma – and combining these terms to emphasize specific data and key issues – CDH1 and gastric carcinoma, CDH1 and colorectal carcinoma, CDH1 and breast carcinoma. Following are the results displayed by the PubMed database after typing these terms:
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Combining the terms relevant to the present study, CDH1 and gastric carcinoma showed 127 peer-reviewed PubMed articles.
Inclusion protocols were developed for the study and were as follows: All peer-reviewed published articles, regardless of their study design and type, were included in the study (case reports, case series, reviews, systematic reviews, meta-analyses, cohort studies, clinical trials). ; Only ‘free-text’ articles were included in the study; Articles published from 1998–2020 were included in this study; Articles found only after typing in the above keywords for study were included in the study; Only articles written in English language are selected. Only articles that met the quality criteria were selected The remaining articles that did not meet the above criteria were excluded from the study. All articles referring to the same population or the same population group were removed from the study.
Peer-reviewed published articles included for the study were reviewed by the primary author following all PRISMA guidelines and meeting the inclusion/exclusion criteria. The review strategy was to find articles that showed associations between CDH1 mutations and gastric and breast cancer and colorectal carcinoma. The main aim of the study was to determine the association of E-cadherin mutation in hereditary diffuse gastric cancer and invasive lobular breast cancer and how it affects.
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