Badania genetyczne
Diffuse Gastric Cancer
We perform genetic testing from:
saliva (the Oragene kit, spitting into a tube is required for sample collection, therefore the kit is not suitable for children under the age of 5)
venous blood collected
Diffuse Gastric Cancer
Mutations in the CDH1 gene, which codes for a protein called epithelial cadherin (E-cadherin), may cause specific types of gastric and breast cancers. E-cadherin plays an important role in the processes of cell adhesion (it helps cells to stick together to form a well-organized tissue). Moreover, it is a tumor suppressor protein that prevents the cell from an uncontrolled growth and division.
Persons who carry a germinal mutation in the CDH1 gene (which means they were born already with one mutated copy of the gene) run during their lifetime a very high risk of losing the activity of the second, normal copy of the gene. When it happens, the cell has no more functional E-cadherin protein and can develop into a cancer cell.
Germinal mutations in the CDH1 gene are found in approximately 30% of families with hereditary predisposition to diffuse gastric cancer (also referred to as linitis plastica). Diffuse gastric cancer is a less common type of gastric cancer and shows a significant correlation with genetic factors as opposed to intestinal gastric cancer, which is usually sporadic and strongly associated with environmental risk factors such as smoking or Helicobacter pylori infection.
The carriers of the mutation in the CDH1 gene are at a lifetime risk of over 80% of developing the diffuse type of gastric cancer. Usually the cancer is diagnosed in their late thirties. The diffuse type of gastric cancer in its early stages is located beneath the intact mucosal surface. As a result, it gives clinical symptoms very late, is highly invasive and extremely difficult to detect early on routine gastroscopy. There exist some diagnostic tools that might be helpful in identifying early diffuse gastric cancer like endoscopic ultrasound or PET scan. Nevertheless, the recommended approach for persons with the mutated E-cadherin protein and a family history of diffuse gastric cancer remains prophylactic total gastrectomy (the procedure of complete removal of the stomach offered to patients before any symptoms appear).
Women with a mutation in the CDH1 gene are at a 60% risk of developing the specific type of breast cancer that begins in the milk-producing glands (lobular cancer). Sometimes the mutation is found in the patients with lobular breast cancer even if there are no gastric cancers in their family. Women who are carriers of the mutation should have breast examination every six months. Apart from an annual mammogram, breast MRI is also recommended as lobular breast cancer can elude mammographic detection. The option of prophylactic mastectomy can be considered, too.
Other malignancy that may be associated with mutations in the CDH1 gene are large intestine and rectum cancers. Additionally, in some patients from at-risk families cleft lip or palate was present.
Mutations in the CDH1 gene are inherited in an autosomal dominant pattern which means that a person carrying the mutation is at a 50% risk of transmitting it to his/her children.
A genetic test for CDH1 gene mutations is specially recommended if:
1. there were two or more cases of diffuse gastric cancer or a case of diffuse gastric cancer and a case of lobular breast cancer in a family (especially when at least one person was diagnosed before the age of 50)
2. only one person in a family had diffuse gastric cancer, but it was diagnosed before the age of 40
3. there were two or more cases of lobular breast cancer in a family (even without any history of gastric cancer)
Literature:
OMIM http://www.omim.org/entry/137215
Genetics Home Reference http://ghr.nlm.nih.gov/condition/hereditary-diffuse-gastric-cancer
R.Fitzgerald et al. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research J Med Genet2010;47:436
I.Kluijt et al. “CDH1-related hereditary diffuse gastric cancer syndrome: clinical variations and implications for counseling” Int. J. Cancer: 131, 367–376 (2012)
S.Shenoy et al. “Hereditary diffuse gastric cancer: genetics, prophylactic total gastrectomy, and follow up” Gastrointestinal Cancer: Targets and Therapy 2011:1 15–19