Familial Gastric Cancers

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 .....Two sets of criteria are used to establish a diagnosis of
HNPCC: (a) Amsterdam criteria and (b) Bethesda criteria.
Gastric carcinoma is not a defining criterion for HNPCC in either
classification......

 Molecular Genetics (Lynch Syndrome)
The most common defect is seen in MSH2, which accounts for ∼60% of HNPCC cases (also known as HNPCC1), and MLH1 accounts for ∼30% of the cases (also known as HNPCC2). Mutations in PMS2, MSH6,TGFBR2, and MLH3 account for the
remaining 10% of the cases. Epigenetic silencing of MSH2 caused by deletions in upstream EPCAM gene results in another variant [105]. It is unclear whether there is a significant variation in the incidence of gastric carcinoma between MSH2
and MLH1 mutated HNPCC cases; conflicting reports have described higher incidences clustering in one subtype versus the other (T33,T34) [106, 107]. Some phenotypic variations are observed, especially between HNPCC1 (MSH2 mutated) and other HNPCC types [105, 108]. of families [106]. Eradication of H. pylori in HNPCC patients may reduce the risk of gastric carcinoma [111]. Routine testing by
immunohistochemistry is recommended for screening all colorectal carcinomas in major academic centers and can detect up to 95% of MMR related CRCs [113]. There are no current screening guidelines at this time for identification and
screening of MSI-H gastric carcinoma by immunohistochemical testing.




BRCA1 and BRCA2 Hereditary Breast and
Ovarian Cancer

In addition, melanoma as well as gastric and pancreatic
carcinomas have been associated with BRCA1 and BRCA2
syndromes [130–132]. Gastric cancer has been reported to be
one of the most frequent cancers in the families of probands
with BRCA mutations in one study, and its incidence before the
age of 70 years is twice as common in these patients compared
with the general population [133, 134]. The association of
gastric carcinoma is reported to be stronger with BRCA2 than
BRCA1, with an increased relative risk of gastric cancer in
BRCA2 mutation carriers (2.59; 95% CI51.46–4.61) [131].The
frequency of gastric carcinoma is 5 times higher than the
general population particularly in Ashkenazi Jews with BRCA2
mutations....

 CONCLUSION
Despite better understanding and control over known risk
factors, gastric adenocarcinoma remains one of the most
common cancers worldwide. Recently, awareness of familial
gastric cancer syndromic predisposition has been emphasized,
because though these syndromes are uncommon, they bear
major management implications for the patients and their
families. This review, while providing concise information
regarding the molecular and histopathologic characteristics of
these syndromes, also aimed to offer updated management
guidelines, including follow-up and surveillance.