Cancer is a disease that is ultimately caused by some change in our genes which is called mutation because all cell function, that is their growth pattern and division, is controlled by our normal genes but due to any reason if they get altered they lead to abnormal division of cells leading to abnormal growth and ultimately cancer.
Genes are the carrier of all instructions for making proteins, which do most of the work in our cells. Certain alteration in the genes can cause cells to have abnormal growth, which is uncontrolled, rapid and becomes cancerous. These altered genes are called cancer genes or oncogenes.
Some examples are some oncogene leads to an increase in the production of a protein that makes cells grow rapidly and uncontrolled. Others result in the production of a non-functional form of a protein that normally repairs cellular damage.
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Genetic changes that promote cancer can be inherited from our parents if there are alterations in germ cells, which are the reproductive cells of the body (eggs and sperm). Such changes, called germline changes, are found in every cell of the offspring.
Carcinogenic substances can cause cancer-causing genetic changes which can also be acquired during one’s lifetime, as the result of errors that occur as cells divide. Carcinogenic substances that damage DNA can be certain chemicals in tobacco smoke, and radiation, such as ultraviolet rays from the sun. Genetic changes that occur after conception are called somatic (or acquired) changes.
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 missing entirely. Other changes involve larger stretches of DNA and may include rearrangements, deletions, or duplications of long stretches of DNA.
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Sometimes the changes are not in the actual sequence of DNA. For example, the addition or removal of chemical marks, called epigenetic modifications, on DNA can influence whether the gene is “expressed”—that is, whether and how much messenger RNA is produced. (Messenger RNA, in turn, is translated to produce the proteins encoded by the DNA.)
In general, cancer cells have more genetic changes than normal cells. But each person’s cancer has a unique combination of genetic alterations. Some of these changes may be the result of cancer, rather than the cause. As cancer continues to grow, additional changes will occur. Even within the same tumour, cancer cells may have different genetic changes.
Almost 10% of all cancers are due to hereditary genetic mutations.
There are various tests available which can tell 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 the obvious disease have inherited the same mutation as a family member who carries a cancer-associated mutation.
Experts recommend that genetic testing for cancer risk be considered when someone has a personal or family history that suggests a cancer risk condition which can be hereditary but the tests should be accurate and should have high predictive value for certain cancer.
Cancers that are not caused by inherited genetic mutations can sometimes occur due to non-hereditary reasons. For example, the same environmental exposure or lifestyle, such as chewing tobacco, smoking, alcohol, can cause similar cancers to develop among family members.
It is not all people having cancer-predisposing mutation present in a family, who inherits the mutation, will necessarily, develop cancer.
Here are examples of genes that can play a role in hereditary cancer syndromes.
The most commonly mutated gene in all cancers is TP53, which produces a protein that suppresses the growth of tumours. Also, germline mutations in this gene can cause Li-Fraumeni syndrome, a rare, inherited disorder that leads to a higher risk of developing certain cancers.
Inherited mutations in the BRCA1and BRCA2 genes are associated with hereditary breast and ovarian cancer syndrome, which is a disorder marked by an increased lifetime risk of breast and ovarian cancers in women. Several other cancers have been associated with this syndrome, including pancreatic and prostate cancers, as well as male breast cancer.
Another gene that produces a protein that suppresses the growth of tumours is PTEN. Mutations in this gene are associated with Cowden syndrome, an inherited disorder that increases the risk of breast, thyroid, endometrial, and other types of cancer.
Genetic tests for mutations that cause hereditary cancer syndromes are usually requested by a person’s doctor. Some genetic counsellors can help people consider the risks, benefits, and limitations of genetic testing in their particular situations.
A genetic counsellor, doctor, or other health care professional trained in genetics can help an individual or family understand their test results and explain the possible implications of test results for other family members.
How to identify genetic changes in cancer
Lab tests called DNA sequencing tests can “read” DNA. By comparing the sequence of DNA in cancer cells with that in normal cells, such as blood or saliva, scientists can identify genetic changes in cancer cells that may be driving the growth of an individual’s cancer. This information may help in designing the specific plan of treatment according to genetic changes which can ultimately lead to the better overall output of the patient.
Tumour DNA sequencing can also reveal the presence of inherited mutations. Indeed, in some cases, the genetic testing of tumours has shown that a patient’s cancer could be associated with a hereditary cancer syndrome that the family was not aware of
In conclusion, most of the cancers are caused by some genetic changes but only 5 to 10 % of these changes are hereditary and rest of the changes are either due to environmental exposure to certain chemicals, radiation exposure, chronic ingestion of toxic substances like alcohol, tobacco either in chewable form or smoking, increased meat in the diet and various other reasons which are very well preventable by living a healthy lifestyle and having more of chemical-free plants based diet.
There are various changes in genes of which cause is still not known so one must be vigilant about early signs of cancer and take immediate advice as “Cancer is curable if detected early”.
(Dr Vishnu Agarwal is Consultant Surgical Oncology, Jaslok Hospital and Research, Mumbai. Views are personal)