How Do Carcinogens Cause Cancer?

Siddhartha Mukherjee: So we’ve talked a little bit about the Cancer Genome. We’ve talked about the genetic changes, but I want to take one step back even before these genetic changes arise. Dr. Schwartzentruber, tell us what we know about how carcinogens cause cancer.

Doug Schwartzentruber: Well that is a challenging question because there are multiple ways for carcinogens to cause cancer and I probably should defer to some of the other panelists as well who have studied that much more than I have, but the obvious first step is how the environment which from the minute we’re born begins to interact and create feedback to say our normal cells that could then potentially be cancerous and maybe I'll stop at that point and lead into others.

Lewis Cantley: Most carcinogens we think cause cancer by mutating DNA, but there are examples of carcinogens, for example, phorbol esters which can cause skin cancers, that almost certainly are not working through mutating DNA directly, although in the long run you always end up getting mutations in DNA. They are rather probably causing cells to grow at a higher rate and the higher the rate cells grow the more frequently they get mutations in DNA. Basically a cell has to go through a division cycle and make a daughter cell in order for a mutation to get locked in. But most really do it by directly damaging DNA, UV light, radiation directly damage the nucleotides in the DNA and many other chemical carcinogens interpolate into the DNA and at the time of cell division interfere with proper base replacement.

Harold Varmus: No, I agree entirely with this, but I would like to add two important points. First we as individuals grow up from a single cell and through many, many rounds of cell division many errors are going to occur because the ability to copy and distribute the three billion base pairs of DNA into daughter cells is an inherently error prone mechanism. We have ways to try to correct it, but nevertheless damage will occur and over the course of many cell doublings there will be damage that can be carcinogenic, so you don’t need to have external factors for cancer to arise. Cancer is probably part of our heritage. Genetic change is a good thing at the species level because we generate diversity throughout living systems.

The other point I would make is that not all carcinogens are UV light or radiation. Some of them are viruses and it’s very important to keep that in mind. It has been estimated that in developing countries for example maybe a third of cancers are caused by viruses. We actually have vaccines that are effective against some of those viruses. The human papillomavirus vaccine, the human hepatitis B virus vaccine can prevent a very large amount of cancer in those countries if the vaccines are made available, brought to patients, made affordable in poor countries. Cervical cancer is largely controlled in this country by pap smears, by early detection, and we only have about 3,000 deaths a year in this country, but in many parts of the world, India for example, and large parts of Africa, cervical cancer is the most common cause of death from cancer among women, and we now have the potential to reduce the incidence of that cancer by two-thirds using the human papillomavirus vaccine.

Seemingly every year there are new reports that something we consume or use on a daily basis is carcinogenic. But what exactly does that mean on a biological level?

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