Developmental biology - Cancer|
Why Tall People Are Prone To Cancer
Increased cancer risk appears to be associated with height and due primarily to an increased number of body cells...
An evolutionary biologist says increased cancer risk is associated with height due primarily to an increase in the number of body cells and thus an increase in cell divisions. For most cancers, risk increases dramatically with our advancing age. But what about the effect of having more cells in the body?
Might taller people be more prone to cancer because they have more cells? Yes, according to Leonard Nunney, at the University of California, Riverside, who examined data from four large-scale surveillance projects focused on 23 cancer categories. Each of these studies established that tall individuals are at an increased risk of cancer, with overall risk increasing by about 10 percent per 10 centimeter (4 inch) increase in height.
Other researchers have proposed that factors early in life - nutrition, health, social conditions - independently influence height and cancer risk. But Nunney, a professor of biology, challenges this hypothesis. "The data strongly supported this simple hypothesis. For most cancers, height effect is predictable from the height-related increase in cell number." His study results appear in the Proceedings of the Royal Society B. When Nunney performed a comparison of the effect of height on the risk of specific cancers for both women and men, he found that being tall increased the risk of thyroid and skin cancer in women; but for men, skin cancer stood out.
Nunney: "Tall individuals are at increased risk of almost all cancers. But skin cancers - such as melanoma - show an unexpectedly strong relationship to height. This may be because the hormone IGF-1 is at higher levels in taller adults."
IGF-1 is a growth factor that is particularly important in early development, but has also been linked to a higher rate of cell division in tall adults.
Nunney explains: "If your cells divide more often, that adds to your cancer risk. If skin cells are dividing more rapidly in tall people due to high levels of IGF-1, then this could account for the increased risk for melanoma." Of the 18 cancers scored in both sexes, Nunney found only four showed no significant increase with height in either sex: pancreas, esophagus, stomach, and mouth. "It is possible that these cancers are more strongly associated with environmental factors. It is possible, too, that in these tissues cell numbers do not scale with body size - but this seems unlikely."
So two factors appear to cause increased cancer risk. One is having more cells. The other is having more cell divisions. "If you double the cells, you double the cancer risk. If you double the number of cell divisions, you more than double the cancer risk. Living a long time is the worst thing to do if you want to avoid cancer. But what's the alternative?"
Men are taller than women on average, which may account for why men get more cancer than women. "About a third of this effect can be accounted for by men having more cells. But something else is going on to explain the rest."
Nunney plans to continue exploring how different cancers are prevented in the body by looking at big, long-lived animals. "If all else is equal, large, long-lived animals should experience higher incidence of cancer than small, short-lived animals. After all, larger animals have more cells, more divisions, and more mutations. But they show no such tendency to be more cancer prone. This is called Peto's paradox, and I believe it can be resolved through adaptive evolution, namely, that species subject to selection for larger body size and greater longevity evolved additional layers of cancer suppression. I'm interested in exploring how as a species gets bigger and lives longer, it evolves additional barriers to cancer."
The multistage model of carcinogenesis predicts cancer risk will increase with tissue size, since more cells provide more targets for oncogenic somatic mutation. However, this increase is not seen among mammal species of different sizes (Peto's paradox), a paradox argued to be due to larger species evolving added cancer suppression. If this explanation is correct, the cell number effect is still expected within species. Consistent with this, the hazard ratio for overall cancer risk per 10 cm increase in human height (HR10) is about 1.1, indicating a 10% increase in cancer risk per 10 cm; however, an alternative explanation invokes an indirect effect of height, with factors that increase cancer risk independently increasing adult height. The data from four large-scale surveillance projects on 23 cancer categories were tested against quantitative predictions of the cell-number hypothesis, predictions that were accurately supported. For overall cancer risk the HR10 predicted versus observed was 1.13 versus 1.12 for women and 1.11 versus 1.09 for men, suggesting that cell number variation provides a null hypothesis for assessing height effects. Melanoma showed an unexpectedly strong relationship to height, indicating an additional effect, perhaps due to an increasing cell division rate mediated through increasing IGF-I with height. Similarly, only about one-third of the higher incidence of non-reproductive cancers in men versus women can be explained by cell number. The cancer risks of obesity are not correlated with effects of height, consistent with different primary causation. The direct effect of height on cancer risk suggests caution in identifying height-related SNPs as cancer causing.
Leonard Nunney PhD.
The University of California, Riverside is a doctoral research university, a living laboratory for groundbreaking exploration of issues critical to Inland Southern California, the state and communities around the world. Reflecting California's diverse culture, UCR's enrollment is now nearly 23,000 students. The campus opened a medical school in 2013 and has reached the heart of the Coachella Valley by way of the UCR Palm Desert Center. The campus has an annual statewide economic impact of more than $1 billion. To learn more, call (951) UCR-NEWS.
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