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You have cancer!
by -- May 3rd, 2016

“You have cancer.”  Not the words that any of us want to hear from our doctor. A first response is to ask how this could have happened. Was it something I did, or was it unfortunate genetics?

In my own case, the answer seemed fairly clear. I had spent about 20 years doing field research in the desert southwest, mostly in the summer to accommodate the academic calendar.  I would guess that my skin cancer was likely due to excessive exposure to the Sun’s ultraviolet radiation—a well known correlate of skin cancer globally.  And luckily, with a few layers of tissue removed, the doctor said that he had gotten it all.

Of course, cancers come in a wide variety of virulence and organs.  What do we know about the intrinsic, genetic predisposition to cancer and what do we know about external, environmental factors that are important?  There seems little doubt that the risk of lung cancer increases significantly with a personal decision to smoke cigarettes—an extrinsic environmental factor that we can control.

One clever, well-known study published more than 15 years ago, examined the co-occurrence of cancer in identical twins. Here, if one twin got cancer, what was the probability that the other twin, with identical genetics, would get the same cancer?   The answer varied among types of cancer, but it seemed that 42% of the risk of prostate cancer, 35% of the risk of colorectal cancer, and 27% of the risk of breast cancer could be linked to the genetics of the twins. Genetics is important, but environmental exposures after birth contributed 50 to 70% of the risk.

The life-time risk for cancer in various organs appears to be associated with the number of normal cell divisions associated with the maintenance of these tissues. Thus, colon tissues, with some of the highest rates of stem cell divisions, are at greater risk of developing cancer, while various types of bone cancer are less prevalent.  Environmental effects may increase the incidence of cancer in tissues that are predisposed to have a high risk due to frequent stem cell divisions.  

The increasing risk of cancer among tissues with high numbers of stem cell divisions appears to have an intrinsic component—bad luck mistakes in DNA replication among cells that replicate a lot.  But all along the regression line, cancers with known extrinsic factors, such as lung cancer, occur at greater frequency than would be predicted by cell divisions factors alone.  From this we can conclude that the majority (70 to 90%) of cancers in various organs arise from exposures to the external environment. Studies of the environment have a lot to offer to medicine.

Some environmental exposures are natural, including exposure to a low level of ionizing radiation from cosmic rays and radioactive decay in the Earth. Hexavalent chromium, well known for its role in Erin Brockovich’s suit against Pacific Gas and Electric, is also found naturally in the environment.

Exposure to radiation is a well-known extrinsic factor that increases the risk for cancer. Exposures to some synthetic chemicals, increasingly prevalent in our daily environment, are also potentially carcinogenic.  It is interesting to note that among women with the BRAC gene, an intrinsic predictor for a high risk of breast cancer, the actual rates of breast cancer at comparable age, are markedly higher for women born after World War II, when we began to embrace “better living through chemistry.”

In the past several years, nuclear power advocates have increasingly questioned the relationship between exposure to radiation and cancer risk, arguing that some level of exposure is “natural.”   Of course, the latter is true.  Background radiation may be responsible for the intrinsic, baseline risk for cancer due to mistakes in DNA replication in rapidly dividing cells. 

Following exposure to low levels of ionizing radiation above background levels, it is difficult to see statistically significant increases in cancer risk.  At higher levels of exposure the risk increases linearly with exposure.  It seems logical to extrapolate the linear relationship at higher levels to predict the risk at lower levels.  The precautionary principle would suggest that there is no level of exposure to radiation at which the risk of cancer is zero.

 

References:

King, M.C., J.H. Marks, and J.B. Mandell. 2003.  Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2.   Science 302: 643-646.

Leiter, U. and C. Garber.  2008.  Epidemiology of melanoma and nonmelanoma skin cancer—the role of sunlight.  Adv. Exp. Med. Biol.  624: 89-103. 

Lichtenstein, P., N. V. Holm, P.K. Verkasalo, A. Iliadou, J. Kaprio, M. Koskenvuo, E. Pukkala, A. Skytthe, and K. Hemminki. 2000.  Environmental and heritable factors in the causation of cancer.  New England Journal of Medicine 343: 78-85.

Wu, S., S. Powers, W. Zhu, and Y.A. Hannun. 2016.  Substantial contribution of extrinsic risk factors to cancer development.  Nature 529: 43-47.

 

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