Meditations of an oncology geek

What is a carcinogen and how does it cause cancer?

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(Back to Cancer for Dummies main page for additional topics)

A carcinogen is defined as anything that can cause cancer. Now, that doesn’t really help much, so I will elaborate.

A carcinogen can be UV rays from the sun. A carcinogen can be cigarette smoke. A carcinogen can be a virus, in the case of HPV and cervical cancer. A carcinogen can be a bacterium, in the case of stomach ulcers. A carcinogen can be age, and the accumulated cell damage from essential every-day biochemical reactions.

Most carcinogens act, directly or indirectly, by promoting DNA damage. Here is the key concept: we are all born with the genes necessary to cause cancer: proto-oncogenes. And, we are born with genes that normally prevent cancer development: tumor suppressors. When they are mutated, they can contribute to the development of cancer.

Image: cigarette smoke is a particularly potent carcinogen, and contains several chemicals that cause DNA damage

All known proto-oncogenes have a normal role that is essential to life, but when altered slightly by a carcinogen, can cause cancer. For example, genes that normally allow tissue to repair itself can instead promote uncontrolled cell growth or cell migration.

I will use an example: B-RAF is a gene that normally encodes a small protein that can send signals to the cell nucleus to tell it to grow. In most melanoma cases, this gene is altered in such a way that it is always turned on. B-RAF is a proto-oncogene. If it acquires a particular re-structuring of the DNA inside the gene, it becomes “Oncogenic K-RAS” or simply an “oncogene.”

Cancer can also be promoted by the mutation of tumor suppressor genes that normally hinder cancer development. An example is the gene p53, which is mutated or lost in roughly half of all human cancers.

In another article I discussed the genetic causes of cancer, and it is important to note that families with genetically heritable cancer will often harbor mutations in a tumor suppressor gene or a proto-oncogene. In a sense, they are one step closer to cancer than the rest of us.

There is no single gene that can cause cancer. A cancer genome (sum of all genes) will contain many, many mutations. Individual genes will be altered slightly or lost entirely, and sometimes entire chromosomes will be in the wrong place. These additional mutations often take years, or even decades to develop, which over time contribute to the hallmarks of cancer, and this phenomenon helps to explain why cancer is an age-related disease.

Our DNA is frequently under attack from many carcinogens. Cosmic radiation, UV radiation, cellular respiration, natural chemicals, artificial chemicals, and other things are common. It is not possible to be a living, breathing human being without coming in contact with carcinogens. What is amazing is how infrequently cancer develops! There are many, many checkpoint mechanisms and biochemical pathways that hinder or stop cancer development in its tracks, and understanding and exploiting these processes has been a major source of innovation of the last 20 years in cancer research.

-Ryon

Written by Ryon

March 6th, 2011 at 5:17 pm

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