Thursday, March 23, 2017

Another Look at Luck and Cancer: Risk Accumulation & Prevention

by Graham Colditz

The debate regarding luck, prevention, and cancer risk is in the media again today (see Science, NPR, Forbes, and many others).

The authors of this new paper -- a follow-up of their original published two years ago and which caused such stir -- make a clear effort too classify cancer risk as due to H - hereditary (our parents - who we cannot change), E - environmental exposures (modifiable risk factors, such as cigarette smoking, weight gain in adult years, and lack of physical activity) and R - rate of DNA damage accumulated as cells divide.  By taking this approach, however, we continue to focus on the underlying rate of division and DNA damage, not the factors that modify this rate and certainly are known to modify cancer risk.

Doll and Armitage showed in 1954 that 5 to 6 mutations were needed to generate cancer in lung, colon, and numerous other organ sites. Yes, the multistage model proposed in 1954 was largely correct based only on assessment of age and cancer mortality in the UK. Of course, back then, treatment did not change outcomes to any great extent.

Today, we have more evidence that the rate of DNA damage varies by age.  For example, breast cancer shows this clearly in animal models and through incidence in women. The stages of a woman's life are associated with different rates of cell division - faster from the time a woman has her first menstrual period to the time she has her first baby, then more slowly after each baby, to even slower after menopause (unless a women uses hormone therapy that consists of estrogen-plus-progestins).

We wrote on this some time ago, (see below) as have many others.



While risk accumulates through cell divisions, we know that avoiding smoking and other major risk factors dramatically reduces the risk of specific cancers.



As the cancer burden continues to increase globally, using what we know from decades of cancer research lets us as a society reap benefits now.  Our return on investment on what we already know is waiting to be collected.  We just need the foresight and political will to do it.

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