Why Do Most People Evade Cancer?

Cancer as a threatening medical condition occurs in a third of all people. Given that tiny, non-threatening cancers exist in all people by old age, why not the other two thirds? The glib answer is that they are killed by something else before a threatening cancer arises. Cancer risk is seen as a continual game of odds, the chance of cancer rising throughout most of life as DNA damage accumulates. The third are the unlucky ones. There is probably more to it than that at the detailed level of cellular biochemistry, however:

Approximately one in three people is struck by neoplastic disease in his or her lifetime. But, the other side of that coin is that two out of three people remain unaffected. Even the majority of heavy smokers, who bombard their lungs with carcinogens and tumor promoters over many years, remain cancer free. Naturally, the suffering of cancer patients and their families has inspired researchers to study the cellular changes unique to cancer and the genetics of cancer susceptibility. The genetics of cancer resistance, as a topic in its own right, has remained largely unexplored.

Pathologists have shown that virtually all men age 60 or older have microscopic prostate cancer when examined at autopsy. Most of these microtumors never develop into cancer, however. It is also known that disseminated cancer cells are present throughout the body in most cancer patients, but only a small minority of these cells develop into secondary tumors. The rest are kept under control by the body. Indeed, metazoan evolution has led to many adaptations that protect species across the animal kingdom from outlaw cells. Immune surveillance plays a major role in the defense against virus-associated tumors, where the virally encoded transforming proteins provide readily recognizable foreign targets. But nonviral tumors, which are composed of aberrant host cells, do not provide such targets, and the immune response is suppressed by defenses against autoimmune reactions. Rather, we now know that the main safeguards against cancer are not immunological at all.

Several cancer-resistance mechanisms appear to have evolved to maintain cellular or genomic integrity. For example, normal stroma, the connective material that supports the cells of a tissue, appears to inhibit cancer growth. Other resistance mechanisms include DNA repair, suppression of oncogene activation, tumor-suppressor genes, epigenetic stabilization of chromatin structure, and apoptosis. These mechanisms are well-studied, and each provides a potential road map for prevention and treatment.

Link: http://www.the-scientist.com/?articles.view/articleNo/42469/title/Resisting-Cancer/

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