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    Cancer and genetic risks

    April 11, 2019

    Cancer is a disease where some of the cells in our body begin to divide uncontrollably and spread into surrounding tissues. In the human body, there are trillions of cells. Cancer can arise in almost any cell in the human body. Normally, human cells grow and divide to form new cells when it is necessary. In the human body, there are several mechanisms to regulate and monitor cell growth. When a cell grows older or becomes damaged, there is an auto-regulated mechanism called apoptosis that instructs the cell to self-regulated programmed cell death. Then a new cell will take that place.
    When cancer develops the apoptosis process of removing damaged or older cells is no longer be function. Cancer cells survive when they should die, and new abnormal cells form when they are not needed. These cancer cells have the special property of dividing uncontrollably irrespective of the inhibitory signals given by the rest of the body. Cancerous tissue can be divided into two main categories, benign and malignant. Benign tumours are local slow-growing and less harmful. Once removed surgically, they re-appear very rarely. But, malignant tumours are completely opposite to benign tumours. Malignant tumours grow rapidly without control and can spread into or invade nearby tissues. In addition, as these tumours grow, some cancer cells can break off and travel to distant places in the body through the blood or the lymphatic system and form new tumours far from the original tumour.
    Genes
    Cancer is a genetic disease. In other words, every cancer has a genetic background.In a normal cell, there are three types of genes which control growth and prevent it from becoming a cancer cell: proto-oncogenes, tumour suppressor genes and DNA repair genes. The changes in these can cause cancer.
    Proto-oncogenes
    They are involved in normal cell growth and division. However, when these genes are altered (mutated) in certain ways (by UV radiation and certain chemicals such as asbestos, benzene, viruses such as Human Papilloma Virus, alcohol and smoking). They may become cancer-causing genes (oncogenes), allowing cells to grow and survive when they should not.
    Tumor suppressor genes
    They are also involved in controlling cell growth and division. These genes will suppress tumour formation. If there is an adverse genetic alteration due to the above-mentioned cases, these genes will lead the cell to natural death. The cells with certain alterations in tumour suppressor genes do not have this capacity and may divide in an uncontrolled manner and become cancerous.
    DNA repair genes
    They are involved in fixing damaged DNA. The cells with mutations in these genes tend to develop additional mutations in other genes. Together, these mutations may cause cells to become cancerous.These genetic changes can be acquired during one’s lifetime (by exposure to various cancer-causing agents as mentioned above) or can be present at birth. Genetic changes can be inherited from parents if the changes are present in germ cells, which are the reproductive cells of the body (eggs and sperms). Such changes are called germline changes and are found in every cell of a child.There are many different kinds of DNA changes. Some changes affect just one unit of DNA, called a nucleotide. One nucleotide may be replaced by another or it may be found missing entirely.
    Other changes involve larger stretches of DNA and may include rearrangements, deletions (loss of a full segment of DNA), or duplications (duplicating the same segment) of long stretches of DNA. These changes may alter the type of protein molecule production and produce unnecessary proteins in the cell (when genetic alteration happens in proto-oncogenes) or not produce the relevant protein in the cell (when genetic alteration happens in DNA repair genes).
    In general, cancer cells have more genetic changes than normal cells. But the cancer in each person has a unique combination of genetic alterations. Some of these changes may be the result of the cancer, rather than the cause. As the cancer continues to grow, additional changes will occur. Even within the same tumour, cancer cells may have different genetic changes.
    Hereditary cancer syndromes
    Certain cancers can run in families. Those types of cancers are called inherited cancers. Inherited genetic mutations play a major role in about five to 10 percent of all cancers. Researchers have discovered mutations in specific genes with over 50 hereditary cancer syndromes, which are disorders that may predispose individuals to develop certain cancers.
    Genetic tests for hereditary cancer syndromes can predict whether a person from a family that shows signs of such a syndrome has one of these mutations. These tests can also show whether family members without obvious disease have inherited the same mutation as a family member who carries a cancer-associated mutation. Many experts recommend that genetic testing for cancer risk be considered when someone has a personal or family history that suggests an inherited cancer-risk condition.
    Cancers that are not caused by inherited genetic mutations can sometimes appear to ‘run in families’. For example, a shared environment or lifestyle, such as tobacco use, can cause similar cancers to develop among family members. Even if a cancer-predisposing mutation is present in a family, not everyone who inherits the mutation will necessarily develop cancer. Several factors influence the outcome in a given person with the mutation.
    Genetic test
    You may consider genetic testing if,* you have several first-degree relatives (mother, father, sisters, brothers and children) with cancer.* many relatives on one side of your family have had the same type of cancer.* a cluster of cancers in your family is known to be linked to a single gene mutation (such as breast, ovarian, colorectal, and pancreatic cancers in your family).

    * a fmily member has more than one type of cancer.
    * family members have had cancer at a younger age than normal for that type of cancer.
    * close relatives have cancers that are linked to hereditary cancer syndromes.
    * a family member has a rare cancer, such as breast cancer in a man or retinoblastoma (a type of eye cancer).
    * ethnicity suggests it (eg., Ashkenazi Jewish ancestry is linked to ovarian and breast cancers).
    * a physical finding is linked to an inherited cancer (such as having many colon polyps).
    * one or more family members have already had genetic testing that found a mutation.
    Next step
    Consult your family doctor and plan to meet with a genetic counsellor or clinical geneticist if cancer runs in your family and you have a reason to think you might benefit from testing.
    A genetic counsellor or clinical geneticist can help you figure out whether testing is right for you and your family. And, if you decide to get tested, a genetic counsellor or clinical geneticist can help you interpret the results. Some genetic tests are available in Sri Lanka and some can be done by sending the samples to foreign laboratories.
    Other factors:
    . Other family members
    Genetic testing results affect not just you; it also affects family members who share the same genes. Not everyone might want to know if they are at increased risk. Learning that you or a family member might have an increased cancer risk can be upsetting. . Tests can lead to more tests
    In some cases, more medical tests, cancer screenings, or procedures may have to be done as a result of genetic testing. This can be a good thing, if other tests help keep you free of cancer or if they find it early when it is likely to be easier to treat. But, the tests can have downsides as well, such as the time and expense involved, as well as possible risks from the tests themselves.
    . Cost
    Genetic tests are expensive. Some tests cost more than others, and the final bill can run into thousands of rupees. Therefore, make sure you have an idea of how much it will cost you before you undergo your test or tests. Before giving your consent for testing, it is your right to know all the details.
    . Insurance
    If you have health insurance, discuss with the insurance provider about the coverage. Certain policies do not cover the costs if you take the insurance after being diagnosed.
    Inherited breast cancers
    According to the data published by the National Cancer Control Programme of Sri Lanka, breast cancer is in the first place. From 2005 to 2014, the number of breast cancer patients have increased drastically.
    Hereditary breast cancer accounts for five – 10 percent of all breast cancers. The majority of inherited breast cancers are due to mutations in two breast cancer genes referred to as BRCA1 and BRCA2. The risks of developing breast and ovarian cancers are higher in carriers of the BRCA1 mutation compared to carriers of BRCA2. In addition, cancer is more likely to occur at a younger age in carriers of BRCA1 mutations than in carriers of BRCA2. An average woman has a 12 percent lifetime risk of developing breast cancer.
    The BRCA1 and BRCA2 mutations also increase the risk of cancers of the ovaries, uterine tubes, peritoneum; specific to BRCA2 mutations, the risk of breast cancer in males, pancreatic cancer and melanoma, increases. All of these conditions collectively compose hereditary breast and ovarian cancer syndrome.
    Both genes are inherited in an autosomal dominant fashion and function as tumour suppressor genes. In other words, this gene can spread via the mother or the father to the son or the daughter. Therefore there is a 50 percent chance of inheritance and genetic testing for BRCA mutations is recommended.
    Angelina Jolie’s story
    In 2013, Hollywood celebrity, Angelina Jolie announced that her mother, grandmother and aunt had breast and ovarian cancers which put her at a significant risk of also developing these cancers. She was tested for the BRCA gene and was found to be positive for the BRCA mutation. She then underwent bilateral prophylactic mastectomies to prevent breast cancer.
    In March 2015, Angelina Jolie underwent laparoscopic oophorectomy or removal of the ovaries to prevent ovarian cancer and she obtained hormone replacement therapy to prevent the side-effects of premature menopause.
    Jolie’s genetic testing and prophylactic surgery led to more than doubling of the demand for the BRCA gene testing in women who would not otherwise have gone for testing but were at high risk for carrying the mutation based on family history worldwide. This was referred to as ‘The Angelina effect’.

     

     

     

     

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