Greaves begins in part one with some potted history, with cases going back to ancient Egypt, a king of Naples and prehistory, and with aspects of early modern medical science and epidemiology. Evolution is involved in three ways: human cancers can only be understood in the context of human evolution; human history has created a "social ratchet", in which environmental and social changes have made once adaptive features and behaviours a source of problems; and cancers themselves are evolutionary phenomena on a rapid time-scale.
Part two explains how cancers work. Cancers are basically clones: "all cancers arise or are initiated and then propelled by gene mutations in single cells". Cancers are a result of "the way we are", "an inherent legacy of our evolutionary and developmental history" and the risks involved in tissue differentiation and controlled cell death. Our systems have evolved to minimize the risk of clonal escape, but cancer remains "a statistical inevitability".
There are many obstacles a cancer must pass to survive and proliferate: removal of constraints on growth, angiogenesis (connection to blood supply), getting around defensive mechanisms, and metastasis. There is often no linear sequence to this process: covert precancerous lesions are common in healthy people, cancers can stop, start and regress without obvious cause, and fast-growing cancers may go nowhere while slower ones "win" the race.
Greaves describes some of the experimental work that has proved genetic links to cancer, and looks at gastric cancer in Napoleon's family as an example. While the results of mutations in genes such as p53 are clear, however, the "composite or mosaic" of factors involved in cancer means that "practical control in the future is unlikely to involve the manipulation of genes".
Cancer cells are immortal and parasitic, but only rarely contagious, even in special cases such as pregnancy and organ transplantation.
In part three Greaves touches on the relationship between aging and cancer and then surveys some of the environments, practices and groups that are linked with cancer. He begins with the best-known example, with a history of tobacco and medical understanding of its cancer risks.
Turning to breast cancer, he argues persuasively that the biggest contribution to the modern "outbreak" are changes in hormonal cycles: women are experiencing more of them, as a result of fewer childbirths, less breast-feeding, and earlier menarche. There may be a similar link between prostate cancer and testosterone levels, though the evidence here is weaker.
Other topics are touched on in less detail: links between viruses, cervical/penile cancers, and sexual activity; the different types of skin cancers and their links with melanin, vitamin D, and human evolution and dispersion; diets and geographical patterns in oesophageal and intestinal cancers; various work-related risks; and X-rays and reactor leaks.
Part four turns to treatment. This is a magnet for quackery and fraud, perhaps because "progress in disease control and eradication has been at best modest for the major adult cancers". Targeting growth is not always useful, cancers are diverse and already primed to avoid DNA damage and apoptosis, and treatment may select for drug immunity. Most successfully tackled cancers are exceptional, originating from special stem cells and having "abbreviated evolutionary trajectories".
Looking to the future, Greaves thinks any kind of "smart bomb" solution is unlikely, and suggests alternative approaches such as targeting angiogenesis. There are many opportunities to reduce risks — further reductions in smoking, controlling cancers where infection plays a role — and patterns in cancer incidence and mortality will continue shifting.
Though not intended as such, Cancer: The Evolutionary Legacy would make a good introduction to cancer, doing some justice to its complexity as a product of genetics, environment, and fundamental aspects of human and cellular biology. It also has plenty to offer for those who already have an understanding of the mechanics of cancer. For those who want more, each of the four sections has notes, with references, and thematically organised further reading suggestions.
January 2008
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