What causes cancer? Part 2 – Inherited mutations

We spoke about how our changing lifestyles have started to contribute to rising cancer rates in recent years in Part 1 of this series on What causes cancer?. Although it is possible for us to control lifestyle factors, unfortunately, 5-10% of diagnosed cancers can be traced back to something those patients inherited from their parents: a genetic mutation that is present in all the cells of the body. Such mutations can and do increase the overall lifetime risk of a person for getting cancer. These cancer cases are then usually referred to as hereditary cancer because the cause was not a random mutation acquired through exposure to cancer-causing materials (like radiation and certain chemicals, read more about this in Part 3 of this series) or brought on by our own lifestyle.

Recent advances in science and technology have allowed researchers and doctors to close the loop on some of the main culprits involved in hereditary cancer. Angelina Jolie family history of cancer reconstructedThe two most commonly talked about genes in this context remain BRCA1 and BRCA2 (pronounced bra-ca). Several mutations in either one of these genes are now known to cause breast, ovarian, or both cancers in those who inherited a mutation. But the list is not complete yet – we still discover new mutations in these genes that can be blamed for cancers across generations in the same family (like in American actress Angelina Jolie’s case whose mother, aunt, and grandmother all suffered and eventually died from breast or ovarian cancer at a relatively early age).

However, there are many more genes involved in the various other types of cancers that are known to have a hereditary component, notably colon cancer, pancreatic cancer, prostate cancer, renal cancer, and medullary thyroid cancer. Science has classified genes involved in causing cancer into three broad categories based on what their normal function is in our bodies. Knowledge about the normal function of a gene also helps explain why a mutated version of such a gene plays such an important role in the emergence of cancer:

  • Tumor suppressor genes – These are the genes that normally protect our cells from growing out of control and forming tumors. They monitor how fast cells divide, repair mistakes introduced to our DNA by the cell division process and control when a cell dies. Examples of such tumor suppressor genes are BRCA1, BRCA2, and p53. In fact, a missing or mutated p53 gene is involved in 50% of all cancers, but most of these mutations are acquired mutations rather than inherited.
  • Oncogenes – These genes have the power to turn a healthy cell into a cancerous cell. However, mutations in these genes are not inherited. Examples for oncogenes are HER2 (you might have heard about this gene in the context of many breast cancers) and the RAS family of genes.
  • DNA repair genes – These are the genes responsible for fixing mistakes that happen when a cell’s DNA is copied before the cell divides. Therefore, if someone has inherited a mutated version of a DNA repair gene, their cells are not able to repair the random mistakes that are introduced quite frequently in the constant process of cell renewal. Some of these mistakes would be harmless, but some will have the potential to cause cancer. One example of an inherited cancer caused by mutations in DNA repair genes is Lynch syndrome (a type of colorectal cancer).

However, this is not a black-and-white picture. Some people carry a known cancer-causing mutation and never develop cancer. Although they remain healthy, there is a 50% chance of that mutation being passed on to the next generation. This son or daughter then carries a similarly high risk of developing cancer and unfortunately, there is still no way of telling if or when cancer will strike. One of the cases in our clinic highlights exactly this phenomenon of an unaffected mother passing on the damaging mutation to her children who then went on to develop cancer early in life (you can read more about this particular example here). This is precisely why it is so important to be aware of one’s family history of cancer.

If you would like to know more about hereditary cancer or suspect hereditary cancer in your family, do not hesitate to reach out to us and speak to one of our genetic counsellors. Call 1800-1022-695 (toll-free in India) or email us at stayaheadofcancer@strandls.com to make an appointment. You can also find out more about hereditary cancer and the tests available to identify hereditary cancer-causing mutations on our dedicated StayAheadOfCancer website: https://www.strandls.com/stayaheadofcancer.