04/03/2017
Paul Spector MD, Contributor Health consultant and writer specializing in prevention and aging.
Cancer is caused by gene mutations that result in an uncontrolled increase in cell proliferation. This breakaway behavior has always been attributed to two factors, environment (E) and heredity (H). A controversial paper now suggests a third source may be responsible for most cancer-causing mutations.
Researchers at Johns Hopkins noticed that the lifetime risk of cancer in 25 different tissues was strongly correlated with the total number of divisions of normal stem cells in those tissues. About three random mutations (R) are known to occur every time a stem cell divides. Mouse models have also indicated that the number of cell divisions predicts cancer risk for many organs.
In an effort to quantify the relative contribution of E, H and R, the investigators tracked the incidence of 17 cancers in 69 countries (a variety of E and H) representing 4.8 billion people, about two-thirds of the world’s population. Their data suggest that as much as two-thirds of cancer is caused by R mutations. These findings are consistent with estimates of the fraction of cancers that can be prevented by changes in the environment.
In other words, there are three major causes of mutations that lead to cancer, environment (E), heredity (H) and random mistakes made during normal DNA replication (R). Unlike mutations caused by E and H, those derived from R are equally distributed in a given age group across all populations.
In examining epidemiological and cancer genome sequencing data from the International Agency for Research on Cancer on 32 cancer types, the investigators calculated what proportion could be attributed to E or H. Those caused by neither E nor H were categorized as R related. After normalization for the incidence of each of the 32 cancers they found 29% attributable to E, 5% to H and 66% to R.
The relative impact of E, H and R has fundamental implications for prevention. For instance 90% of the most common form of lung cancer is preventable. Here, E plays the lead role predominantly through tobacco smoke and H has essentially no part. On the other hand, E appears to have little effect on brain, bone and prostate cancers where R probably dominates.
This research may provide an explanation for the unpreventable component of cancer risk that has long plagued epidemiologists. It does not however diminish the importance of primary prevention. The authors point out that a cancer in which 50% of the mutations are due to R can still be prevented. More than one mutation is usually required to cause disease. If one mutation was due to R and the other to E, primary prevention could be effective.
Cancer incidence increases exponentially with age. The global increase in human lifespan has made cancer the most common cause of death. This new data may allow for more effective targeting of research and treatment in our battle with this complex disease.
