40 DNA Mutations and Cancer

What is Cancer?  How do Cells become Cancerous?

Cancer is characterized by the accumulation of cells due to excessive rates of cell cycling and/or lack of apoptosis.  Often cancerous cells no longer respond to normal cues to exit the cell cycle and unfortunately continue to repeatedly undergo cell division.  Cancer can also occur when cells no longer respond to cues to become dormant and undergo apoptosis.  As a result of impaired control of rates of cell cycling and/or apoptosis, cells begin to accumulate forming a mass, which can spread, not only negatively affect neighbouring tissue but also disrupting distant locations throughout the body that cancerous cells migrate to.

Impaired Control of Cell Cycling and Apoptosis      

You may recall that the cell cycle consists of interphase (consisting of 3 phases:  G1 phase, S-phase, and G2 phase), and mitosis (consisting of 4 stages: prophase, metaphase, anaphase, telophase), following by cytokinesis.  In the process of 1 cell cycle, 1 cell grows, duplicates its organelles and DNA and then divides into 2 identical daughter cell.  This entire process is tightly regulated by specific genes known as regulator genes.  For example, there are regulatory genes that code for growth factors that stimulate cell cycling as well as growth-inhibiting factors that limit the rate of mitosis.

Regulator genes code for growth factors and growth inhibiting factors, controlling the rate of mitosis and apoptosis (cell death).  Mutations in regulatory genes can lead to excessive mitosis or a lack of apoptosis, contributing to cancer development.

There are several causes of DNA mutation, which include:

• Viruses (e.g., Human Papilloma Virus, HPV is considered an oncovirus in that it can mutate DNA and has been linked to the development of cervical cancer),
• Radiation which includes:
  • UV light is a risk factor for skin cancer as it can cause thymine dimers in DNA which leads to errors during DNA duplication,
  • Gamma rays are associated with radioactive isotopes which have been found to cause DNA mutations),
• Chemicals (e.g., asbestos, cigarette smoke), and
• Spontaneous errors during DNA synthesis.
• Rapid rates of mitosis during injury repair may increase the risk of errors occurring, potentially leading to cancer.

Terry Fox is a Canadian Hero who attempted to run across Canada in order to raise money in support of cancer research. Of course, we know he started in St. John’s Newfoundland and was stopped short in Thunder Bay when the cancer had spread to his lungs and he could no longer run.  Until that point, he had been running the distance of one marathon per day for 143 days.  This is an astounding feat given that one of his legs had been amputated due to cancer of the bone and he was running with the use of a fairly rudimentary (and certainly not comfortable) prosthetic limb.  Terry Fox had a cancer called osteosarcoma. Now, before he was diagnosed with cancer in that that bone, he’d actually been in a in a vehicle accident and had sustained damage to that same leg.   When he was later diagnosed with cancer in that same leg, he thought it was quite the coincidence. He started speculating this, maybe during the healing of his leg, cancer had formed.  During healing when there were rapid rates of mitosis, it may have been that DNA errors were created in regulatory genes that caused cells to become cancerous.  Terry’s Marathon of Hope was stopped short and he died at age 22 as the cancer metastasized to his lungs.

Cancer is a Disease of the Genes? 

It may seem odd that cancer is considered a genetic disease as it is rarely inherited, and more often is acquired through exposure to various mutagenic risk factors (some of which are mentioned above).  Cancer is certainly a disease caused by gene mutations, specifically in regulatory genes required for cell cycling and/or apoptosis as well as for ensuring proper and error-free DNA duplication.  To date over 290 different gene mutations have been linked to cancer.

What is the difference between a genetic disease, an inherited disease and a congenital disease?

Although some cancers are inherited (e.g., retinoblastoma), most inherited diseases are not cancerous.  For example, Cystic Fibrosis and Huntington’s Disease both occur when DNA mutations are inherited.  In both of these cases the DNA mutations occur in genes that are involved other cellular processes that do cause problems, but do not result in cancer.

Side note:  Not all congenital diseases are inherited or genetic.  Congenital is a term that translates to “born with”.  For example, cerebral palsy is a congenital disease, though it is not genetic and is not inherited.  Cerebral palsy is thought to occur when a brain lesion takes place either before or shortly after birth.