The paper analyzes the role of different genetic variants involved in Lynch syndrome , an inherited disease that increases the risk of various tumors
The study is published in the journal Nature Genetics and has had the participation of Gabriel Capellá and Marta Pineda, form the Hereditary Cancer Program at the Catalan Institute of Oncology ( ICO- IDIBELL)
An international study has developed a refined method to identify people at risk for certain inherited cancer as a result of Lynch syndrome.
The study, published in Nature Genetics have carried out clinical and researchers who are part of the INSIGHT (International Society for Gastroeintestinal Hereditary Tumours ) . Coordinated by Maurizio Genuardi , University of Florence, and Finlay Macrae , Royal Melbourne Hospital , at work and have participated Capellá Marta Gabriel Pineda, Hereditary Cancer Program at the Catalan Institute of Oncology ( ICO- IDIBELL) .
The research is funded by the Spanish Ministry of Science and Innovation and the Scientific Foundation of the Spanish Association Against Cancer .
All cancers are caused by abnormalities in the genetic material of cells , that make them lose their function and become malignant .
Lynch syndrome is an inherited condition that increases your risk of colon cancer and other cancers. Lynch syndrome has historically been known as hereditary nonpolyposis colorectal cancer (HNPCC).
A number of inherited syndromes can increase your risk of colon cancer, but Lynch syndrome is the most common. Doctors estimate that about 3 out of every 100 colon cancers are caused by Lynch syndrome.
Families that have Lynch syndrome usually have more cases of colon cancer than would typically be expected. Lynch syndrome also causes colon cancer to occur at an earlier age than it might in the general population.
Gene mutations associated with Lynch syndrome
People with Lynch syndrome have a mutation in one of 4 genes that normally correct mistakes when deoxyribonucleic acid (DNA) is copied during cell division. These genes are called DNA mismatch repair genes (MMR).
The 4 main MMR genes associated with Lynch syndrome are MLH1, MSH2, MSH6 and PMS2. Most mutations (90%) that cause Lynch syndrome are found in the MLH1 or MSH2 genes. The other 2 genes, MSH6 and PMS2, and possibly others, account for the other 10% of mutations.
Researchers have also identified different gene mutations associated with Lynch syndrome, but these are rare. Other mutations may be discovered in the future.
In 90 or 95 % of cases of people with cancer are born with genes functioning properly until, by external factors, for errors that may occur during normal DNA replication or by the passage of time, the genetic material , which had always worked properly, breaks down. When genes embrace alterations or mutations, the cells do not perform its function properly.
A small percentage of people are born with an error in the genetic material that greatly increases the chances of developing cancer. When this is the main cause for the occurrence of the disease, we talk about hereditary cancer or hereditary cancer predisposition. It is estimated that only between 5 and 10% of all tumors are hereditary.
Chances of inheriting Lynch syndrome
Men and women can inherit a gene mutation associated with Lynch syndrome from either their mother or father. People with one of these mutations can also pass it on to their children. If one parent has the mutation in 1 of the 2 copies of a Lynch syndrome gene, a child has a 50% chance of inheriting the gene mutation. This also means there is a 50% chance that a child will not inherit the gene mutation.
Healthcare professionals use certain criteria to determine if a Lynch syndrome gene mutation may be present in a family. These are referred to as the Amsterdam criteria.
- At least 3 family members have colorectal cancer or another cancer related to Lynch syndrome. At least 1 of these family members is a first-degree relative (parent, sibling or child) of the other 2 family members.
- At least 1 family member was diagnosed with cancer before age 50.
- Cancer occurs in at least 2 generations in a row.
- FAP has been ruled out.
Lynch syndrome, also called hereditary nonpolyposis colorectal cancer polyposis (English HNPCC) is an inherited disease that increases the risk of various tumors , especially colon and endometrial cancer , being responsible for between 2 and 5 % of cases .
Research published in Nature genetics has focused on studying the genetic causes of Lynch syndrome. Often the result of the genetic study of patients with this syndrome is not informative , since relevance of genetic variants is unknown: one can not predict their biological significance and clinical implications. It is therefore unknown whether these patients have a higher risk of developing other cancers , or if their family members are also at risk .
The research team collected data from thousands of genetic variants identified in genes repairers worldwide, responsible candidates for Lynch syndrome . There has been a global effort to refine this information in a public database . The model, which has used the expertise of researchers and clinicians from around the world with the knowledge of the syndrome , which essentially allowed sequencing data can be translated into clinically useful information .
Through this cooperative effort it has achieved the classification of a large number of variants of unknown significance . The classification of a variant responsible for Lynch syndrome is critical for genetic counseling of families, allowing predictive study of families at risk and , if they are carriers , help them take preventive measures and adequate monitoring .
Institut d’Investigació Biomèdica de Bellvitge