Throughout most of the twentieth century, age-adjusted death rates for many of our most common cancers were vastly lower in much of the Third World than in comparatively wealthy industrialized countries such as the United States. These types of cancers thus became known as “Western cancers.” They include cancers of the breast, prostate, colon, ovary, uterine endometrium, and pancreas – cancers that, along with tobacco-induced lung cancer, constitute the main causes of cancer mortality in the U.S. today.
Why have these cancers been so less common in poorer societies? The most reasonable current explanation seems to be that, in poor societies, blood levels of two key growth factors – insulin and free insulin-like growth factor-I (IGF-I) – tend to be much lower than in wealthier countries. Insulin and/or IGF-I stimulate the proliferation of the epithelial tissues from which these cancers arise. They also inhibit the process of apoptosis, which is an important way in which the body gets rid of cells which have sustained mutagenic DNA damage. The combination of increased proliferation – which makes DNA damage more likely – and suppression of the mechanism that rids the body of mutated cells, is a potent stimulus to cancer induction.
What aspects of a Western diet and lifestyle are primarily responsible for our higher levels of insulin and free IGF-I? We speak of “free” IGF-I because there are various proteins in the blood that bind to IGF-I, rendering it inactive. Only the unbound “free” IGF-I can interact with cell receptors. Factors such as abdominal obesity, fatty diets, especially those rich in saturated fats, and sedentary lifestyle are typically associated with increased blood levels of insulin. Under these conditions, skeletal muscle becomes less sensitive to the glucose-transporting activity of insulin. Because of insulin resistance, the body tends to increase the secretion and slow the removal of insulin to compensate for this. This increase in insulin levels tends to increase blood levels of free IGF-I, since insulin acts on the liver to boost IGF-I production while also slowing the production of a binding protein, IGFBP-1, that antagonizes IGF-I’s activity.
Another lifestyle factor that promotes increased IGF-I levels is a relatively high intake of “high quality” protein. In Third World societies where people eat a mostly plant-based vegan diet, total daily protein intakes tend to be relatively low. The proteins consumed tend to be lower in certain nutritionally essential amino acids, such as methionine, for example, than the “high quality” animal proteins that predominate in Western diets. The relative paucity of certain essential amino acids in vegan diets of moderate protein content can lead to a decrease in the liver’s production of IGF-I, and an increase in IGFBP-1 production. It’s no coincidence that, in rural China, where most people have eaten a quasi-vegan diet for centuries, the provinces with the highest intakes of animal protein are the ones at highest risk for most types of cancer. This has been revealed by the world’s most ambitious epidemiological investigation, the China Study.
These considerations imply that lean people who consume quasi-vegan diets that are low in fat and moderate in protein, and who get regular exercise, can be expected to have relatively low levels of both insulin and free IGF-I, and to enjoy decreased risk for Western cancers. At least until recently, a high proportion of people in Third World societies fit this description. As noted, the relatively high levels of insulin and free IGF-I characteristic of “advanced” societies can act directly on their target tissues to promote cancer induction. They can also act in indirect ways to boost cancer risk. In particular, this pattern of hormone activity tends to accelerate sexual maturation in girls and increase blood levels of free sex hormones. These circumstances are known to increase risk for breast and endometrial cancers. Obesity, per se, increases estrogen levels in postmenopausal women, as fat cells are capable of producing estrogen from other circulating steroid hormones fruit.