The majority of cancers are “sporadic.” This means they are the result of environmental exposures or possible random events within a cell. Therefore, these cancers are genetic, however they are not hereditary.
Familial and hereditary cancers are thought to consist of 35% of all colorectal cancers and a significant portion of other cancers.
A familial cancer is a hereditary cancer that may be due to shared environmental or lifestyle factors.
Hereditary cancers, such as Lynch syndrome, result from an inherited gene mutation or variant that is present in every cell and can be passed onto the children.
Lynch syndrome is the result of a mutated gene. To make sense of this, we need to think of the composition of our bodies, which are made of millions of cells.
Each of these cells has 23 pairs of chromosomes and within the chromosomes are genes. These genes are lined up on the chromosomes in a very specific manner. When a gene is not normal or when some chromosomes are forgotten or duplicated, defects in the body or within its system can occur, some of which can be mild defects or some as serious as Lynch syndrome. In those of us who have Lynch syndrome, a gene stopped working that usually works to prevent colon, endometrial and other Lynch cancers. Therefore, the cancers are likely to develop…and at a younger age.
There are four common basic mutations known to date, including MLH1, MSH2, MSH6 and PMS2, as well as EPCAM and a few lesser known. These genes are involved in repairing mistakes in DNA which may occur when the cell goes through the division process. Mistakes in DNA can occur due to environmental factors (i.e., exposure to chemicals, drinking impure water, etc.) however environmental mistakes do not ordinarily create inherited cancers.
Epcam deletions can create Lynch syndrome. The EPCAM gene is a recently discovered contributor to Lynch syndrome, accounting for an estimated 1-3% of all detectable Lynch syndrome mutations. Studies indicate that large deletions in the end of this gene can lead to a loss of MSH2 expression and result in Lynch syndrome.
With the exception of the environmental mutations and one percent of those with Lynch syndrome possessing what is known as a “de novo” mutation (meaning new and not known previously in which no known family members have/had Lynch syndrome), all other mutations are hereditary and are created by germline mutations, or rather those created during the reproduction process (in the egg or in the sperm.)
Lynch syndrome cancers are extremely aggressive and don’t have the extended “dwell time” (time tumors live and exist in the body until becoming cancerous) as other cancers, thus the reason it is very important to obtain regular surveillance testing.
Currently, there is no gene therapy, which is commonly referred to as a “cure” for Lynch syndrome, however researchers are working feverishly in an attempt to find a way to neutralize the “rogue genes.” Technology is being explored which will work sort of like an automobile gas pedal…as the gas is pressed which creates the acceleration of the cancer formation, the brake is pressed at the same time, so the vehicle will not move forward or backward. Of course, this technology, if possible, is many years away and in the absence of a cure, the closest thing to a cure is genetic testing.
Genetic testing is essential toward survival. With diagnosis, individuals can obtain yearly surveillance testing during which time if pre-cancerous or cancerous polyps are discovered, they can easily be removed at an early stage– when treatment is most effective. Without early prevention, individuals develop cancers at an aggressive rate and with metastases, survival becomes more difficult.
A genetic test is ordinarily taken from a standard blood or saliva sample, which is processed within a clinical laboratory. A positive result for Lynch syndrome (HNPCC) makes one a “mutation carrier” and not only diagnoses an individual with Lynch syndrome but also serves as verification of having an increased risk for cancer. That risk is then monitored by one’s health provider with surveillance measures and an annual testing regiment.
If there is a mutation which has previously been identified within the family and the test result of that specific mutation comes out negative, then it is determined one has no increased cancer risk and the individual does not have a mutated gene. Any and all cancer screening will be based upon the same screening given the general public.
If a mutation has not been previously identified in the family and a comprehensive panel has not identified a mutation, then it is determined that a cancer risk is not fully defined and is unknown. As a result, based on the personal and family history of cancer, medical management for screening and surveillance will be determined.
Most individuals who are diagnosed with Lynch syndrome, by genetic testing, sing praises as to the benefits. Not only are they monitored closely by medical professionals, their families also have an opportunity to be protected and to live longer lives.
Psychologically and emotionally, changes occur within those who test positively. The “unknown family cancer thing” suddenly has a name and there is hope and empowerment in being able to control it. The wait is over and stress and anxiety is relieved.
For some, it is a relief. For others, it is bittersweet. And for some, testing does have its limitations and isn’t perfect. Not all causes of hereditary cancer can be detected and though a negative result is extremely helpful when there is a known mutation in the family (thus being a true negative,) there is always the fear the negative may not truly mean “negative” in the absence of a family mutation. In that case, the uncertainty will continue to exist, however if one meets the criteria for Lynch syndrome, they can and should receive annual screenings for cancer, the same as an individual who has been diagnosed with a known mutation. Finally, testing has not fully evolved and there are other genes out there that have yet to be discovered, as well as variants continuing to be discovered.
So, dependent upon your family history, your needs and understanding of genetic testing, its important to speak with your genetic counselor and your health care provider to determine if testing is good for you and for your family.
According to the National Cancer Institute, general population studies have indicated the majority of individuals, internationally, are not adverse to genetic testing for hereditary cancers but more concerned as to whether or not treatment for the hereditary condition would be available. For resources where to obtain low cost or no cost treatment for those without insurance, view the link marked “Support” to your left and scroll down to the country or state in which you reside.
Study results also indicate a primary motivation for individuals submitting to genetic testing is a concern and a desire to provide protection for their children and loved ones, as well as the ability to reasonably determine for themselves what could occur in the future– in order to make decisions as whether or not to bear children, engage in certain occupations, determine where to reside and in making other major lifestyle choices.
With enhanced surveillance and known successful treatment methods, hope has never been greater than it is today, for individuals with Lynch syndrome and with genetic testing, individuals have all the tools they need for an enhanced quality of life.
