Causal connections between spontaneous mutations and cancers

Abstract

Cancers are diseases due to somatic mutations of two types; activation of oncogenes and inactivation of tumor suppressor genes. In childhood, retinoblastoma arises due to two mutations of the Rb genes, one is hereditary or somatic and the other is somatic. However, most cancers arise at older ages as a result of a succession of several mutations. For example, incidence of colorectal cancer increases with about fifth power of age. This relationship means that colorectal cancer arises as a result of successive five mutations in oncogenes and tumor suppressor genes. Incidences of colon cancers are very high in rich countries and low in poor countries including Japan at the years before 1970, showing a strong linear correlation between daily meat consumptions and colon cancer rates. This correlation seems to indicate that daily consumption of high amounts of meat stimulates clonal expansion of precancerous cells, resulting in formation of malignant colon cancers. This may be the case of a Darwinian selection of fitter cells. In an epidemiologic study carried out in 1984 on Japanese Zen priests, who rarely took meat in daily diet, they showed significantly lower mortality from all causes and cancers of respiratory tracks than men in the general Japanese public. Incidence of cancer of intestine except rectum for the Zen monks was lower, though not statistically significant, than that of general Japanese men. These results indicate that cancer incidences may be prevented considerably by change in our life style.