Editing Hereditary diffuse gastric cancer


HDGC

* An inherited form of diffuse-type gastric cancer

== Genetics ==

* Autosomal dominant
* High penetrance
* Germline variant in either of two genes
** CDH1 (codes for cadherin 1 or e-cadherin/epithelial cadherin)
*** Located 16q22.1
*** Wide range of pathogenic variants (about 2800 found so far)
*** E-cadherin is a tumour suppressor gene because it normally helps with cell adhesion - when lost, cells move around and metastasise more freely - somatic second hit is required
** CTNNA1
*** Codes for alpha catenin which assists with E-cadherin-mediated cell-cell adhesion

== Diagnosis ==

* Presence of a pathologic germline variant in either CDH1 or CTNNA1
* Either an isolated individual or in a family with one or more cases
* Criteria for genetic testing - consensus guidelines from the International Gastric Cancer Linkage Consortium (IGCLC)
** Family criteria - any of
*** Two or more gastric cancer cases in a family regardless of age, at least one confirmed DGC
*** One or more cases of DGC at any age, and one or more cases of lobular breast cancer at age <70 years, in different family members
*** Two or more cases of lobular breast cancer in family members <50yo
** Individual criteria (any of)
*** DGC <50yo
*** DGC at any age in Maori people
*** DGC at any age in an individual with a personal or family history (first-degree relative) of cleft lip/palate
*** Personal history of DGC and lobular breast cancer, both diagnosed <70yo
*** Bilateral lobular breast cancer diagnosed at age <70yo
*** Gastric in situ signet ring cells or pagetoid spread of signet ring cells on a gastric biopsy in individuals <50yo
** Testing can occur 16-18yo, but taking into account the age of earliest cancer in the family

== Risks ==

* Gastric cancer
** Risk 37-42% in men and 25-33% in women by age 80
** Varies depending on exact variant
** Average age of onset 38 years (range 14-82)
** Tumours are often multifocal and located beneath an intact mucosal surface
** Typically results in abundant intracellular mucin, pushing the nucleus aside in a typical signet ring phenotype
* Breast cancer
** Lobular type
** 42% lifelong risk for women
** Risk starting around age 30
* Some other cancers described, but no evidence of particularly increased risk

== Presentation ==


== Screening (until prophylactic surgery) ==

* Annual gastroscopy at a minimum (counsel as to inadequacy of gastroscopy/biopsies for surveillance)
** PET scan not useful for screening
* Annual breast surveillance - MRI starting age 30

== Surgery ==

* Prophylactic gastrectomy
** Prophylactic total gastrectomy by a surgeon experienced with HDGC, from age 20-30
*** Distal margin 1cm beyond pylorus with frozen section to confirm squamous mucosa
*** Conservative harvest of peri-gastric nodal tissue along greater and lesser curvatures, but preserve omentum
*** D2 not necessary
*** Reconstruction is not standardised - often Roux-en-Y
** Recommended for any person with confirmed disease
** Appropriate age 20yo, or five years younger than earliest cancer in the family
** May choose to delay for various personal reasons, in which case counsel the patient and continue screening
* Prophylactic mastectomy

[[Category:Oncology]]