GARLiC - Aug 2020

Project title:
Estimations of diffuse gastric cancer risks in CTNNA1 pathogenic variants carriers
(GARLiC: GAstric Risk Level in CTNNA1)

Project leader:
Chrystelle Colas ; genetic department, Institut Curie, Paris , FRANCE

Project Description:
Gastric cancer is related to a hereditary predisposition in 1-3% of cases. The CDH1 gene, which codes for E-cadherin, is the main cancer predisposition gene identified in families meeting “familial hereditary diffuse gastric cancer” criteria; but it explains only 20% of them. The CTNNA1 gene is a good candidate to be a second diffuse gastric cancer predisposition gene because it codes for alpha-catenin, which is a E-cadherin partner. Some pathogenic variants in this gene were found in evocative families. In the absence of data about cancer risk associated with its variants, CTNNA1 is not always included in germline testing panels. The aim of this study is to evaluate gastric cancer for carriers of CTNNA1 pathogenic variants.

We collected data about carriers of CTNNA1 pathogenic or likely pathogenic variants’ carriers from all available literature and non-published cases. Authors were contacted to update their data. Unpublished families were identified through international collaborations : especially through ERN GENTURIS (4 centers). Recruitment continued until April 2021 and was open to ERN GENTURIS and non–ERN GENTURIS centers.

The cumulative risk of gastric cancer by age for mutation carriers (also known as penetrance function) was estimated with the Genotype Restricted Likehood method, taking into account not genotyped individuals and conditioning on family ascertainment criteria to obtain unbiased estimates. To use this method it iss necessary to have general population incidence data for the type of cancer, which were provided by the French epidemiological registry FRANCIM. Linkage analyses with the LOD score method were also carried out.

Start date: August 2020

Duration: 1 year

Funder: -