Understanding Cancer Genetics

Cancer is a disease which common man understands as a tumor or abnormal growth in a part of the body, which gradually spreads and is incurable. Cancer is not always a tumor. It may develop without tumor also as in the case of blood cancer. But there is lot more to cancer that just a tumor or abnormal growth. We must understand what causes cancer?

Cancer is predominantly a genetic disease, meaning, certain changes to the genes responsible for cell functioning, cell division and cell death, causes cancer.

How does cells become cancerous?

Normal cell cycle includes certain genes carrying the instruction to make proteins to carry out cell division, maintaining the optimal health of the cells and cell death. A different group of proteins are assigned with the individual tasks out of the cell proliferation, cell maintenance and cell death.

So, these proteins may seem mutually exclusive of each other, but they are closely linked. The proteins carrying cell death must be in coordination with the proteins carrying out cell division otherwise the total number of cells in certain tissues will gradually decrease. Similarly, the proteins responsible for cell division must act in tandem with the proteins responsible for cell death otherwise the number of cells will increase in the particular tissue.

This uncontrolled growth of cells which is not able to maintain an equilibrium between the number of cells dividing and the number of cells dying within a specific period of time is called Cancer.

Fig 1: Image showing the stages of cancer development
Adapted from : Cell Biology WebBook

As discussed, the entire process is regulated by different proteins, so one may ask what the role of genes is in causing cancer.

Well, the answer is that the proteins are produced by amino acids, which are produced by the mRNA (messenger RNA) which in turn are transcribed from DNA. So, a change/error in DNA will pass on to mRNA, which will synthesize a wrong amino acid and the wrong amino acid will participate in the production creating a wrong protein. Accumulation of wrong protein creates a series of events which causes cancer, as described earlier.

Is cancer always caused by a genetic change?

For all kind of cancers which exists today, most of them have been attributed to changes in genetic structure. However, only a few have been validated to be direct cause of genetic changes, other have been proved to be affected by certain genetic changes. In other words, we can say that almost all cancer are affected by genetic changes, directly or indirectly

Is cancer always hereditary?

The answer is Yes and No.

If the genetic change that is responsible for promoting cancer is present in the germ cells (sperm and egg), the cancer may be passed on to the next generation making it hereditary. These are called germ-line mutations.

Mutations that causes cancer can also be acquired during one’s lifetime due to many reasons which may include but not limited to, probability of error during DNA replication, exposure to carcinogenic chemicals like ethidium bromide, lifestyle issues, exposure to carcinogenic radiations like UV-rays, exposure and prolonged use of known cancer causing agents like tobacco and smoking. These are called somatic mutations. Somatic Mutations do not travel down to offspring.

Types of DNA changes affecting cancer genetics

There are many different kinds of DNA changes. This may include changes in the single location (nucleotide) where one base is replaced by another. A different type of mutation also occurs frequently where an entire region of few or many nucleotide is either deleted or inserted or repeated or rearranged.

Besides these changes, some mutations do not directly affect the sequence of nucleotides on DNA but affect the degree of expression of the gene. In such situations, the gene sequence may be intact, but the degree of expression may be hampered to such uncontrolled levels that the DNA may over-express or under-express, leading to imbalance in all the subsequent steps of DNA to mRNA to amino acids proteins productions.

Some cancers are caused by single type of mutations whereas some are caused by a combination of mutations. However, once the mutation has successfully initiated cancerous growth of cells, the risk of other genes undergoing mutation is significantly increased due to imbalance in cell cycles.

How to detect mutations?

There are a lot of ways and methods to identify the presence of the mutation in certain gene. With advancements in the molecular biology in recent times, it is possible to check all the genes that may have established role in all the types of cancers within a span of 2-3 days by Next Generation Sequencing.

Most often such methods are not required as the patients’ symptoms may indicate the possibility of specific cancer and then only those genes which have role in promoting that specific cancer might needed to be checked for mutations.

Sanger sequencing is currently the most widely used fast, accurate and cost-effective method for detection of mutations. It enables detection of specific mutations in specific genes.

Selecting the best platform for mutation detection

Opting for the detection of targeted mutation detection for the patient suspected of carrying cancer is the best approach to rule out or confirm the presence of mutations. Each type of cancer may be caused by specific individual or set of mutations, so the selection of genes to be targeted for mutation detection by sequencing or any other methods must be discussed by the certified oncologist.

Also, there are significant number of published studies which report the percentage distribution of mutations among the patients carrying specific cancer. So, the decision on whether to target all genes at once or step by step and in which order is best left to the certified oncologist

Read about: Top 5 Genetic Testing companies in India for Cancer

Which cancers should be screened for genetic changes?

There are many cancers where genetic screening becomes necessary for proper treatment. The genetic changes in cancer often decide the course of treatment of certain anticancer drugs. Presence or absence of certain genetic variants decide if an individual will be likely to get benefit from certain anti-cancer drugs.  Alternative therapies may be prescribed for individuals not treatable by routine drugs.

Following cancers are usually screened for genetic changes:

  1. Breast Cancer and Ovarian Cancer
  2. Leukaemia or Blood Cancer
  3. Colo-Rectal Cancer
  4. Prostate Cancer
  5. Other solid tumour cancers.
Types of cancer affected by germline (inheritable) mutations
Adapted from : ScienceDaily

The above list is not comprehensive. These just indicate the widely prevalent cancers. Certified Oncologist will determine your cancer type and associated genetic changes.

Who should be screened for Cancer Genetics Screening?

Cancer Genetics Screening is done to identify a healthy individual’s risk of developing a cancer. It is generally done for individuals with a family history of cancer. Presence of certain mutations may put them at risk to develop cancer. However, with proper guidance and precautions cancer can be avoided.

Read about: Carrier screening benefits to screen cancer genetics changes

Opinion

Cancer Genetics and understanding the underlying causes is a very broad segment. It is beyond the scope of this platform.

It is advised that people should understand the benefits of cancer genetics testing and should go for it, if their oncologists prescribe it. There are infinite benefits of genetic testing in cancer patients. Cancer Genetics Testing at early stage of cancer may give better understanding of the cancer progression. A decision can then be made within time for a suitable chemo/immunotherapy. Such timely decisions can made a significant disease in survival rate of the patient.

Share this article:

Leave a Reply

Your email address will not be published. Required fields are marked *