Gastric carcinomas in the Tervueren shepherd and Groenendaelers.
An update on the current research unravelling the genetic cause of gastric carcinomas in the Tervueren Shepherd and Groenendaelers.
Sanne Hugen (DVM) and Paul Mandigers (DVM, PhD)
Dr. P.J.J. Mandigers. DVM, PhD, Dip ECVN, Dip RNVA - Internal Medicine
European Board Certified Specialist EBVS
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, PO BOX 80.154, 3508 TD Utrecht, The Netherlands
Dr. Paul Mandigers (projectleader)
Drs. Sanne Hugen (promovenda)
Dr. Peter Leegwater – geneticist
Dr. Hille Fieten – geneticist
Prof. dr. Jan Willem Hesselink (Promotor)
As of 2003 Paul Mandigers has been engaged in mapping the incidence of gastric carcinomas in the Belgian Shepherd. Being the owner of a Malinois and Tervueren Paul started to identify cases and sample them for DNA extraction. In 2012, with the help of the Nederlandse Vereniging voor de Belgische Herder (NVBH) and the charity foundation Dutch Cancer Foundation for Animals (NKFvD), we started a PhD project (with Sanne Hugen, DVM and owner of a Groenendaeler as PhD student) to investigate the genetic cause of gastric carcinoma’s in the Tervueren shepherd and Groenendaeler. In this paper we will try to shed some light on where we are now and what challenges we are facing.
Stomach cancer is unfortunately a big problem and potential threat to the breed. Based on a survey performed in 2009 and a more recent one in 2013 we sadly conclude that, despite the current selection, that the frequency does not drop.1,2 There are two major reasons for this. First of all the disease affects mainly older dogs. Exact knowledge on the dogs we are using might be incomplete or worse we are using dogs that get affected at older age. This means that we might have used dogs that were affected or closely related to affected dogs. And the inheritance is complex. Based on our statistical analyses using the pedigree data from all long-haired Belgian Shepherds, diseased and healthy dogs, we must conclude that there is a clear genetic component. However we are not looking at a simple monogenetic disorder. Other factors play a role. And this is problematic as gastric carcinoma, is based on our data, a serious treat for the breed. The identified number of cases is around 2%, but most likely the death rate due to GC is around 4%. And these are only the affected animals. In an earlier study we calculated the heritability grade to be 0.2%.1 Hence there is room for selection but it might not be easy.
What did we do so far?
We have so far identified over 200, Dutch, cases. From 120 of these dogs we have obtained a full history, DNA isolated as well as gastric carcinoma tissue. Next to this we have a dataset of over 160, thanks to the efforts of many volunteers, control dogs that were, at the time of sampling, healthy and had no stomach upset.
To gain greater insight into gastric cancer in all its facets we conducted an extensive literature review.2 In this review the knowledge of gastric cancer in humans is taken into account and compared. This provides many insights into possible relevant aspects of the dog. If you are interested in the full article, please let us know. We send it to you like.
As written above we have a full history of most cases and healthy controls. This type of information is for our epidemiological study, and phenotyping, very important. Last year we re-evaluated the histology of all cases and this helped us phenotype them as well. We will publish this study in the near future.
When it comes to research into the genes and genetic factors that are involved in GC we performed last year a GWAS on 48 animals and 48 controls. We compared the coding DNA of cases and healthy dogs. We found two regions of interest. We analysed all genes of interest in these two regions but up to now we did not find a significant abnormality. So sadly enough none of the possible candidate genes in these two regions were affected. It does not say it isn’t there.
What are we doing now?
We can increase the power of our GWAS by adding another 48 cases and 48 healthy dogs. But we will also do a so-called full genomic analysis of a few highly selected cases and controls. We expect that this type of research will help us to go future in getting away from this disease.
Research investigation such a difficult disease can only be done if we have funding. The charity foundation NKFvD has supported us generously with over 30.000 euro but that has not been enough. At the moment we need, to complete the study, at least 36.000 euro.
It is for this reason that we started out to cry for help. Please donate. If each Belgian Shepherd owner would donate 10 or 20 euro we would be able to finish our study and help this beautiful breed. We have set up a bank account for this project.
The bank account details are:
NL 52 ABNA 0970301391
2. Hugen S, Thomas RE, German AJ, Burgener, IA and Mandigers PJJ. Gastric carcinoma in canines and humans, a review. Vet Comp Oncol 2016. August.