- For Whom?
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The ColonScreentest is performed when the family has:
• Tumors that arise at a young age
• Several individuals affected by the same type of cancer or correlated cancers
• Individuals affected by multiple tumorsIn particular:
• A known mutation in the family in one of the genes associated with colorectal cancer/polyposis susceptibility
• Colorectal cancer diagnosed ≤ 50 years
• Endometrial or ovarian cancer with a family history of gastrointestinal cancer
• Subjects with more than one cancer associated to the Lynch syndrome (e.g. colorectal and endometrial cancer)
• Three or more cases of colorectal, ovarian, endometrial, gastric cancer or other types of cancer associated with the Lynch syndrome in the family;
• Results of the Microsatellite or immunohistocemical instability test showing a lower capacity of repairing DNA replication errors
• Multiple primary tumors in the same patient
• Several members of the family (on the same side) with colorectal cancer or other types of cancer - What is diagnosed?
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ColonScreenis a diagnostic test aimed at evaluating the susceptibility to the development of Colorectal cancer or Familial Adenomatous Polyposis.
The genetic susceptibility test is addressed to people who, from a thorough family history, show a high and concrete incidence of neoplasms in previous generations and, therefore, have a high risk of carrying a germinal mutation.
ColonScreen®
A diagnostic test aimed at evaluating the susceptibility to the development of Colorectal cancer or Familial Adenomatous Polyposis
Procedure
The ColonScreentest is carried out with a blood sample. The DNA is isolated from the nucleated cells through a complex laboratory analysis and amplified via PCR. Then, with a state-of-the art process Massive Parallel Sequencing (MPS) that uses Next Generation Sequencing (NGS) techniques with ILLUMINA sequencers, 12 genes (exons and adjacent intrionic regions, ± 5 nucleotides) that are usually involved in most cases of hereditary predisposition to the development of Colorectal cancer or Familial
Adenomatous Polyposis are completely sequenced at high reading depth).
The resulting genetic sequences are analyzed with an advanced bioinformatics analysis, to find out if there are any mutations.
What are the benefits of performing the test
- Awareness that the genetic mutations may be transferred to the offspring and the detection of high-risk offspring with germinal genetic mutations
- Finding family members with a high risk of developing cancer
- The development of an adequate medical check plan for high-risk subjects, in order to promote early diagnosis of cancer
- The possibility to undergo prevention therapies
Statistics
HNPCC - Hereditary Non-Polyposys Colon Cancer
The HNPCC (Hereditary Non-Polyposis Colon Cancer - HNPCC), also known as Lynch Syndrome, is an autosomal, dominant cancer with two phenotypes:
Lynch Syndrome I,
with the onset of a colon neoplasm at around 45 years of age
Lynch Syndrome II,
which, in addition to colon cancer, includes the development of extracolonic neoplasms, at an endometrial, ovarian, urinary tract and biliary duct level.
The HNPCC is caused by a recurring mutation in one of the 4 genes that are currently known to be involved in the check and repair of DNA replication errors in all the cells of the body. Around 90% of mutations occur in MSH2 and MLH1 genes (60% in MSH2 and 30% in MLH1) and only rarely involve PMS1 and PMS2 genes. When a mutation occurs in one of these genes, the ability to repair errors during DNA duplication decreases and, as a consequence, mutations accumulate in the cells, leading to a neoplasm.
According to statistics, the risk for the general population to develop colon cancer in life is around 6%. For patients (both male and female) carrying HNPCC mutations, the risk of developing colon cancer is around 75-90%.
Familial Adenomatous Polyposis (FAP)
The Familial Adenomatous Polyposis (FAP or Adenomatosis coli or Colorectal Familiar Polyposis) is a relatively rare syndrome that occurs, usually at an early age, with the development of hundreds to thousands of adenomas on the large intestine. Without treatment, FAP progresses almost invariably with one or more colorectal carcinomas, usually when the individual is 30 to 50 years old; the onset of malignant lesions may be seen with careful endoscopic checks and prompt surgical intervention. The FAP is a "compulsory" precancerous condition, because the person that is affected and not treated will almost certainly develop invasive carcinoma.
The FAP is a hereditary, autosomal, dominant disorder, usually at high penetration. Therefore, a careful analysis of the family history could help detect subjects at risk after which accurate endoscopic checks must be carried out. Presently, this process is easier, thanks to the detection of the gene that, once mutated, generates the disorder (APC gene, Adenomatous Polyposis Coli).
In a sub-type of patients, a mutation of the MUTYH (1p34.1) gene leads to an automosal recessive polyposis, the familial adenomatous polyposis linked to the MUTYH, which is characterized by a small increase in the risk of developing colorectal cancer and polyps/adenomas in the higher and lower gastrointestinal tract.
If ColonScreenhas a negative result
No mutations:
the results show no mutations in the examined genes. However, a negative result does not necessarily mean that the patient does not risk developing a tumor. These people have the same chance of developing cancer as the general population.
If ColonScreenhas a positive result
Presence of one or more mutations:
the results show that there are one or more mutations in one (or more) genes leading to hereditary susceptibility to the development of Colorectal cancer or Familial Adenomatous Polyposis ; the test, therefore, shows a mutated copy of the gene.
A positive result does not necessarily mean that the patient with a mutation will develop a tumor; it only shows susceptibility to developing that type of tumor in the patient, or rather, the person has a higher risk level compared to a person without that specific mutation. In fact, not all people carrying mutations develop neoplasms. Although such mutations significantly increase the chance of developing a tumour, the cancer does not develop until the normal copy of the corresponding gene is mutated during the life of the person.
Since everyone inherits two pairs of the same gene, a mutation must occur in each pair to cancel the function of such gene. The acquisition of a new mutation may, therefore, directly lead to a tumor. Identifying cancer-susceptibility mutation allows us to develop an intense clinical check plan and evaluate preventive surgery.
Accuracy and test limits
Present DNA sequencing techniques are more than 99% accurate. One must remember that:
ColonScreenevaluates only the genetic diseases and the genes listed. The test does not evaluate other genetic diseases or genes not listed.
A “NEGATIVE” result- (no mutations result for the examined genes) does not exclude the possibility that one is a carrier of a mutation that is in a region of the genome that was not explored during the examination. In some cases, the results of a genetic analysis can show a variation or a DNA mutation with a clinically uncertain result not yet known or classified by the medical and scientific community. The interpretation of genetic variations is based on the most recent knowledge available at the time of the analysis. Such an interpretation could change in the future when new scientific and medical information regarding the genome structure and could influence the evaluation of these variations.
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