Reproductive Cancers as an Evolutionary Mismatch Disease

Although I read The Story of the Human Body: Evolution, Health, and Disease over a month ago, the part about reproductive cancers has continued to haunt me:

Early physicians such as Rigoni-Stern noticed and wondered why nuns were far more likely to get breast cancer than married women (for years, breast cancer was known as the “nun’s disease”). These observations were later bolstered by large-scale studies that showed that a woman’s chances of developing breast, ovarian, or uterine cancer increase significantly with the number of menstrual cycles she experiences and decrease with the number of children she bears. Decades of research now indicate that cumulative exposure to high levels of reproductive hormones, especially estrogen, is a major cause of these associations. Estrogen acts widely throughout the body but is a particularly potent stimulator of cell division in a woman’s breasts, ovaries, and uterus. During each menstrual cycle, levels of estrogen rise (as do other related hormones, such as progesterone), causing cells that line the wall of the uterus to multiply and enlarge in preparation for a fertilized embryo to implant. These surges also stimulate breast cells to divide. Thus, when women cycle they repeatedly experience high doses of estrogen, which cause reproductive cells to proliferate, each time increasing the chances for cancerous mutations to occur and increasing the number of copies of any mutant cells. However, when a woman becomes a mother, by getting pregnant and then nursing, she lowers her risk of breast and other reproductive tissue cancers by reducing her exposure to reproductive hormones. Breast-feeding may also help flush out the lining of the mammary ducts, removing potentially mutant cells.

The association between estrogen and some other estrogen-related hormones with reproductive cancers highlights why these diseases are evolutionary mismatches influenced by a chronic state of positive energy balance. Remember that for millions of years natural selection favored women who devoted whatever extra energy they had toward reproduction, partly through the action of reproductive hormones such as estrogen. Natural selection, however, never geared women’s bodies for coping with long-term surfeits of energy, estrogen, and other related hormones. As a result, women today are very different and vastly more at risk of developing cancer than mothers from long ago because their bodies are still functioning as they evolved to have as many surviving children as possible. The result is that women who have more energy also have a greater cumulative exposure to reproductive hormones that, in abundance, elevate the risk of cancer.

Meanwhile, men have high rates of prostate cancers for similar reasons:

A relationship between energy surpluses and reproductive cancer may also apply to men, although less strongly. One of the many functions of the major male hormone, testosterone, is to stimulate the prostate gland to produce a milky fluid that helps protects sperm. Prostate glands are constantly producing this fluid. Several studies show that lifetime exposure to high levels of testosterone increases the risk of prostate cancer, especially in men who live in developed countries and in frequent positive energy balance.

Exercise is a straightforward anecdote to this modern malaise for the simple reason that the more energy spent running, swimming, and lifting weights, the less energy available to produce an abundance of hormones:

Because reproductive cancers are mismatch diseases that are linked via reproductive hormones to a surfeit of energy, physical activity has potent effects on the rates of some cancers. This makes sense: the more energy your body spends on physical activity the less it can spend on pumping out reproductive hormones. Women who are physically active have estrogen rates about 25 percent lower than those who are sedentary. These differences may partially account for why several studies have documented that just a few hours a week of moderate exercise substantially lowers the risk of many cancers, including those of the breast, uterus, and prostate. Several of these studies have found that the more intensive the exercise, the lower the cancer risk. In one study of more than 14,000 women divided into low, moderate, and high fitness groups, those who were moderately fit had 35 percent lower rates of breast cancer, and those who were very fit had more than  percent lower rates of breast cancer (after controlling for age, weight, smoking, and other factors.)

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