Hereditary Diffuse Gastric Cancer: A Family Diagnosis and Treatment

Onitilo, Adedayo A.; Aryal, Govinda; Engel, Jessica M.

doi:10.3121/cmr.2012.1071

Cited by 17 publications

(11 citation statements)

References 23 publications

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“…HDGC, unlike the sporadic forms of gastric cancer, is composed of signet ring cells and originates diffusely throughout the gastric submucosa[ 4 - 6 ]. The sporadic form of gastric cancer is usually associated with Helicobacter pylori infection, which can lead to gastric atrophy and intestinal metaplasia[ 4 , 5 , 7 , 8 ].…”

Section: Discussionmentioning

confidence: 99%

Hereditary diffuse gastric cancer: One family’s story

Zylberberg

Sultan

Rubin

2018

WJG

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Hereditary diffuse gastric cancer (HDGC) is an inherited form of gastric cancer that carries a poor prognosis. Most HDGCs are caused by an autosomal dominant genetic mutation in the CDH1 gene, which carries a 70%-80% lifetime risk of gastric cancer. Given its submucosal origin, endoscopic surveillance is an unreliable means of early detection, and prophylactic gastrectomy is recommended for CDH1 positive individuals older than age 20 years. We describe the case of a male with recurrent gastric cancer who was diagnosed with HDGC secondary to the CDH1 mutation, and we also describe the patient’s pedigree and outcomes of recommended genetic testing.

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Section: Discussionmentioning

confidence: 99%

Hereditary diffuse gastric cancer: One family’s story

Zylberberg

Sultan

Rubin

2018

WJG

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“…First degree relatives of GC patients are known to have twofold to threefold increased risk of GC. This shows the importance of informing family members about positive mutation results, facilitating a faster testing, diagnosis and treatment (Garziera et al 2013 ; Onitilo et al 2013 ). The optimal age to screen individuals from affected families is unclear.…”

Section: Discussion and Evaluationmentioning

confidence: 99%

“…Currently, there are not reliable methods for early detection, and GC patients have often a poor prognosis since it is often detected at advanced states, more aggressive and difficult to treat, being considered not curable (Black et al 2014 ; Garziera et al 2013 ; Onitilo et al 2013 ). Annual endoscopic surveillance is recommended but direct visualization with endoscopy tends to detect lesions late in the disease process and multiple random endoscopic samples often returns false negatives.…”

Section: Discussion and Evaluationmentioning

confidence: 99%

A novel mutation in the CDH1 gene in a Spanish family with hereditary diffuse gastric cancer

López¹,

Cervera-Acedo²,

Santibáñez³

et al. 2016

SpringerPlus

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Hereditary diffuse gastric cancer (HDGC) is an inherited form of diffuse type gastric cancer. Germline CDH1 mutations have been identified in approximately 15–50 % of affected kindred that meet the clinical criteria for HDGC. If any of the criteria is met the individual is referred to genetic counseling and CDH1 testing is offered. In this report we present the case of a Spanish family with HDGC harboring a novel CDH1 mutation. A 47 year-old female with a diagnostic of gastric adenocarcinoma and some of her relatives were tested. Study of the entire CDH1 gene, including intron–exon boundaries, by PCR and sequencing and immunohistochemical determination of the expression of E-cadherin were performed. A novel heterozygous deletion in exon 9 of CDH1 gene (c.1220_1220delC, p.P407Qfs10), was found in the proband, one sister and a nephew. It generates a premature stop codon giving rise to a truncated protein that leads to a pathogenic variant. Expression of E-cadherin was absent or frankly reduced in the proband’s tumor but normal in tumor cells of great-uncle. After these results, the sister underwent prophylactic total gastrectomy, and the nephew is under annual endoscopic surveillance. Personal or familial history of diffuse gastric cancer, above all at young age, should encourage CDH1 genetic testing. In this sense, the review of the criteria and the addition in the last guideline of the recommendation: “other families in which genetic testing may also be considered” broadens the number of individuals at risk detected. Since there are not reliable methods for early detection, DGC is usually diagnosed at an advanced stage and consequently associated with a poorer outcome. Thus, CDH1 mutations detection contributes to an improvement in diagnosis and therapeutic intervention.

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“…It is thought that EMT facilitates detachment of the tumor cell in the primary tumor site, migration and colonization of secondary organs [55, 56]. Inherited mutations in E-cadherin are associated with familial forms of gastric and breast cancer [57, 58]. Moreover, oncogenic pathogens often target this protein [59, 60]: Helicobacter pylori oncoprotein CagA interacts with E-cadherin blocking its binding to β -catenin; as a result, β -catenin accumulates in nucleus where it transactivates gene p 21 WAF 1 important for cell cycle progression, and CDX1 , which is associated with intestinal metaplasia [61, 62].…”

Section: The Role Of Chronic Inflammation In the Pro-tumoral Immunmentioning

confidence: 99%

Protumor Activities of the Immune Response: Insights in the Mechanisms of Immunological Shift, Oncotraining, and Oncopromotion

Chimal-Ramírez

Espinoza-Sánchez

Fuentes‐Pananá

2013

Journal of Oncology

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Experimental and clinical studies indicate that cells of the innate and adaptive immune system have both anti- and pro-tumor activities. This dual role of the immune system has led to a conceptual shift in the role of the immune system's regulation of cancer, in which immune-tumor cell interactions are understood as a dynamic process that comprises at least five phases: immunosurveillance, immunoselection, immunoescape, oncotraining, and oncopromotion. The tumor microenvironment shifts immune cells to perform functions more in tune with the tumor needs (oncotraining); these functions are related to chronic inflammation and tissue remodeling activities. Among them are increased proliferation and survival, increased angiogenesis and vessel permeability, protease secretion, acquisition of migratory mesenchymal characteristics, and self-renewal properties that altogether promote tumor growth and metastasis (oncopromotion). Important populations in all these pro-tumor processes are M2 macrophages, N2 neutrophils, regulatory T cells, and myeloid derived suppressor cells; the main effectors molecules are CSF-1, IL-6, metalloproteases, VEGF, PGE-2, TGF-β, and IL-10. Cancer prognosis correlates with densities and concentrations of protumoral populations and molecules, providing ideal targets for the intelligent design of directed preventive or anticancer therapies.

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Hereditary Diffuse Gastric Cancer: A Family Diagnosis and Treatment

Cited by 17 publications

References 23 publications

Hereditary diffuse gastric cancer: One family’s story

Hereditary diffuse gastric cancer: One family’s story

A novel mutation in the CDH1 gene in a Spanish family with hereditary diffuse gastric cancer

Protumor Activities of the Immune Response: Insights in the Mechanisms of Immunological Shift, Oncotraining, and Oncopromotion

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