THE SILENT KILLER
Family history
and
cancer risks
chances of hereditary cancer to be passed onto offsprings
Cell’s behaviour is controlled by coded messages called genes. Our body’s growth and development depend on gene control. When the body’s normal control mechanism fails to work properly, and the coded messages sent are changed, it results in formation of abnormal cells. The old cells do not die, instead, they grow out of control and start forming new cells. When this happens, the cell is said to have become faulty or have undergone some mutation. Usually, it needs at least 6 or more faulty cells for it to become cancerous. These faulty genes could happen anytime in a lifetime, however there are slight chances that these faulty genes are actually inherited and have been passed down from the parents. Even so, out of all cancers, only around 5-10% cases are caused by the defective gene that is inherited from the parents.
The thing with hereditary cancer is that it is not the cancer itself that is passed down, instead, it is the faulty gene that can lead to cancer that is passed down to the offspring. That means that the offspring will become a carrier of the abnormal gene. The individual carrying the abnormal gene will have a higher probability of getting cancer compared to other individuals without the genes. For example, the mean percentage of women getting ovarian cancer in a lifetime is 2%, however, when a woman carries the BRCA mutated gene, her chance of getting ovarian cancer is increased to about 10-60%.
Generally, there are two possible ways of passing down the defective gene to offspring. It depends on the type of defective gene itself, whether it is an autosomal dominant inheritance or an autosomal recessive inheritance. If the gene is passed down through autosomal dominant inheritance, there will be a 50% chance that the offspring will inherit the abnormal gene, that is if only one parent is a carrier.
Example genes with this inheritance is BRCA1 and BRCA2 (breast, ovarian or prostate cancer), TP53 (sarcomas, brain tumors, leukemia), NF1 (Neurofibroma, optic nerve glioma, nuerofibrosarcoma) and some other genes. Meanwhile, for autosomal recessive inheritance, both parents must be a carrier and pass down the abnormal gene. Each parent is normal and does not have cancer but they each own a defective gene. In this case, the children have 50% chance of inheriting one copy of defective genes and 25% chance of inheriting a copy of both defective genes. These children will become a carrier and may pass the gene on to their offspring later in life. Examples of genes involved in autosomal recessive inheritance are the MUTYH (colon cancer, colonic adenoma), ATM (non-Hodgkin’s lymphoma, leukemia) and FANC (hematological neoplasm).
HOW FAMILY HISTORY REALLY AFFECTS YOUR CANCER RISKS
Most of the time, people whose relatives have cancer do not even inherit the faulty gene. However, when a lot of your family members got the similar or related types of cancer, it might be a hint that there is an abnormal gene that is being passed down the generations. Usually, for hereditary cancers, the age when diagnosed plays an important role too. When it comes to inheriting faulty genes which causes cancer, the cancer will start to show itself earlier (around age 40-50years) compared to people who do not inherit the gene. In order to find out whether you have a family history of hereditary cancer or not, you can try to construct a pedigree using information of members of your family who have also had cancer. A famous name who has a family history of hereditary cancer is a Hollywood actress, Angelina Jolie.
The above pedigree was constructed by using the information that we were able to gather about Ms Jolie’s family members and history of cancer in her family. As is shown in the pedigree, Ms Jolie’s history with cancer went as far back to her great-grandmother, Virginia Gouwens. Ms Gouwens was diagnosed with ovarian cancer which also became the cause of her death at the age of 53. Ms Jolie’s maternal grandmother also reportedly passed away due to cancer at such a young age. Aside from that, Ms Jolie’s mother and aunt, Marcheline and Debbie Bertrand were also diagnosed with cancer. Debbie Bertrand had breast cancer before she died in 2013 and her sister, Marcheline Bertrand was diagnosed with both breast and ovarian cancer and passed away at the age of 56.
With such a heavy family history of cancer, Ms Jolie was determined to get tested for any possibilities of inheriting the mutated gene. After getting a genetic test, the results came out and it was estimated that Ms Jolie had 87% risk of getting breast cancer and about 50% risk of getting ovarian cancer due to presence of the BRCA1 mutated gene. With a high percentage risk of getting those two cancers, Ms Jolie opted to undergo a few preventative surgeries, which are double mastectomy and Salpingo-oophorectomy (ovaries and fallopian tube removal surgery), in hope to be able to lower down her risk of getting cancer or maybe even save her from cancer.
As you can see, the types of cancer that they had were related to each other by the type of mutated gene. The faulty gene that was passed down along the generation was BRCA1 gene which could cause breast, ovarian or prostate cancer. Also, they all were diagnosed with cancer at quite a young age.
There are a few types of genetic testing, namely newborn screening; diagnostic testing; carrier testing; prenatal testing; preimplantation testing; and the predictive and presymptomatic testing. Based on the Angelina Jolie case, the type of genetic testing used is most probably the predictive and presymptomatic testing or the diagnostic testing. Predictive and presymptomatic testing is used when you have family members with a certain type of genetic disorder, but the person being tested has not yet started showing any symptoms of the disorder. On the other hand, diagnostic testing is used to detect or rule out a specific genetic or chromosomal condition. Usually, this method is used to confirm a diagnosis based on the indicated symptoms. This testing can be performed at any point of one’s life, however, not all genetic conditions can be tested using this method. Results from this testing can be used as an indicator of one’s health and could influence their choices in lifestyle in order to cope with the disease.
Other types of genetic testing include:
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Newborn screening is done right after the birth of a baby in order to detect genetic disorders that can be treated early in life before it gets worse. For example, phenylketonuria (intellectual disability due to genetic disorder) and congenital hypothyroidism.
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Carrier testing is done to detect one copy of a faulty gene that when present in two copies, will cause a genetic disorder. Usually, people with a history of a genetic disorder or people of a specific ethnic group that has a higher chance of developing a genetic disease will be tested using this method.
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Prenatal testing is done to identify changes in the genes or chromosomes of a foetus. This test will only be conducted if the baby has an increased risk of a genetic or chromosomal disorder. It will be done during the pregnancy period itself.
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Preimplantation testing is carried out on embryos that are produced through in-vitro fertilization by taking a small number of cells from the developing embryo and testing them for certain genetic changes. Embryos that do not have any genetic changes will be implanted inside the uterus to initiate a pregnancy.
There are a few steps that need to be taken before conducting a genetic test. Usually, if you have a strong family history of cancer that is related to possible genetic mutation, your genetic counsellor would encourage you to get a genetic test. The general practitioner (GP) will decide whether you are eligible for genetic testing or not. It will be decided based on 3 factors, depending on which family members of yours had the cancer, the type of cancer they are diagnosed with and also their age of when they were diagnosed.
In order to get tested for inherited faulty genes, a relative who was already diagnosed with cancer will be tested to see if they have a faulty gene. If the result confirms that the relative indeed does have the faulty gene, then you can have a blood test to detect exactly the same type of faulty gene. You should consult your geneticist after receiving the result of a genetic test to figure out what treatments or changes in lifestyle would best fit you.
GENETIC TESTING
Genetic testing is a test used to detect mutations or changes in DNA sequence or chromosome structure that may cause genetic illness or disease. Genetic testing is able to provide some vital information for the diagnosis, preventing and treating certain illnesses, however, there are limitations to this. For example, if your genetic testing result came out positive, it does not necessarily mean that you will develop an illness. In other situations, if the result came out negative, it does not guarantee that you will never develop a certain disorder. This is why you should always consult a geneticist or a genetic counsellor after getting your results so that they will be able to go through your history and suggest the best possible solution to your problems.
