Germline mutations in hereditary diffuse gastric cancer

Abstract

Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Among which, about 1%-3% of gastric cancer patients were characterized by inherited gastric cancer predisposition syndromes, knowing as hereditary diffuse gastric cancer (HDGC). Studies reported that germline mutations are the main cause of HDGC. With the help of rapid development of genetic testing technologies and data analysis tools, more and more researchers focus on seeking candidate susceptibility genes for hereditary cancer syndromes. In addition, National Comprehensive Cancer Network (NCCN) guidelines recommend that the patients of HDGC carrying mutations should undergo prophylactic gastrectomy or routine endoscopic surveillances. Therefore, genetic counseling plays a key role in helping individuals with pathogenic mutations make appropriate risk management plans. Moreover, experienced and professional genetic counselors as well as a systematic multidisciplinary team (MDT) are also required to facilitate the development of genetic counseling and benefit pathogenic mutation carriers who are in need of regular and standardized risk management solutions. In this review, we provided an overview about the germline mutations of several genes identified in HDGC, suggesting that these genes may potentially act as susceptibility genes for this malignant cancer syndrome. Furthermore, we introduced information for prevention, diagnosis and risk management of HDGC. Investigations on key factors that may have effect on risk management decision-making and genetic data collection of more cancer syndrome family pedigrees are required for the development of HDGC therapeutic strategies.

RETRACTED: Downregulation of long noncoding RNA LINC01419 inhibits cell migration, invasion, and tumor growth and promotes autophagy via inactivation of the PI3K/Akt1/mTOR pathway in gastric cancer

“…As a major cause of cancer-related deaths worldwide, gastric cancer (GC) continues to be a clinical stumbling block for both patients and health care providers. 1 The risk factors for GC include, smoking, male gender, and atrophic gastritis, all of which have been noted to contribute to the incidence of GC. 2 Most GC patients are diagnosed at more advanced stages, characterized by malignant proliferation, extensive invasion, and lymphatic metastasis, all of which are commonly accompanied with high mortality.…”

CDH1 Gene Mutation Hereditary Diffuse Gastric Cancer Outcomes: Analysis of a Large Cohort, Systematic Review of Endoscopic Surveillance, and Secondary Cancer Risk Postulation

“…Quality of life has been routinely correlated to postsurgical outcomes, with up to half of patients expressing decisional regret in the first four weeks following surgery, with slow resolution [ 21 , 70 ]. The advent of multigene panel testing has also led to the discovery of a myriad of CDH1 mutations, for many of which clinical significance has not been established [ 71 , 72 , 73 , 74 ]. Patient counseling requires a multidisciplinary team approach to manage the host of genetic, surveillance, surgical, nutritional, and psychosomatic considerations of this unique population.…”

Incidence of Hereditary Gastric Cancer May Be Much Higher than Reported

“…A few molecular germline mutations are currently recognized as causal events related to these cases [ 29 ]. There are formal recommendations for carriers and their relatives in these situations [ 30 , 31 ].…”