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3. EPIDEMIOLOGY OF CANCER

Julian Peto (Institute of Cancer Research, UK) present an extensive review of current research in cancer epidemiology, the author making the following points:

1) The author points out that many types of cancers vary in incidence by more than an order of magnitude between different populations, and every type of cancer is rare in some part of the world. The convergence towards local cancer rates seen among immigrants excludes a genetic explanation of these differences. By the 1960s, cancer epidemiologists had therefore concluded that most cancers are in principle preventable and that many cancers could be avoided by a suitable choice of lifestyle and environment. Many specific causes of cancer are now known, the most important being smoking, obesity, and a few oncogenic viruses, but a large proportion of global variation for common cancers such as breast, prostate, colon, and rectum remains unexplained.

2) The most important discovery in the history of cancer epidemiology is the carcinogenic effect of tobacco. Lung cancer incidence increases rapidly among continuing smokers, so the risk is greatest in those who begin to smoke when young and continue throughout life. For many years, the carcinogenic effects of tobacco were believed to be restricted largely to the lung, pancreas, bladder, kidney, larynx, mouth, pharynx, and esophagus. More recent evidence indicates that the risk for several other types of cancer, of which the most important worldwide are stomach, liver, and probably cervical cancer, are also increased by smoking.

3) No single dietary factor shows a strong and consistent enough effect to establish it unequivocally as an important carcinogen or anti-carcinogen. Extensive research during the past two decades has shown that rates for various cancers correlate fairly consistently with certain aspects of diet, but opinions still differ on the strength of the evidence. There is now a consensus that cancer is commoner in those who are overweight, with evidence strongest for post-menopausal breast cancer and cancers of the endometrium, gall bladder, and kidney, but several other sites contribute to the overall risk.

4) Breast cancer incidence is transiently increased by pregnancy and while estrogens are administered as oral contraceptives or hormone replacement therapy, and breast cancer incidence is permanently lowered by late menarche, early menopause, early first childbirth, and high number of pregnancies (high parity). The development of cancers of the testis and prostate may also depend on hormonal effects, but apart from the increased risk associated with an undescended testis, no behavioral or reproductive correlate is strongly predictive of these diseases.

5) The most important discoveries of the past two decades in cancer epidemiology relate to the carcinogenic effects of infectious pathogens that had not been characterized 20 years ago. Helicobacter pylori, a chronic gastric bacterial infection that can cause gastric ulcers, is a major factor in the stomach cancer. Some variety of human papillovirus is detectable in virtually all cervical cancers worldwide. Such viruses are also found in other anogenital cancers and may also cause cancers of other sites (head and neck esophagus, skin). The contribution of hepatitis-B virus to liver cancer has long been recognized, although the synergistic effect of smoking is a more recent discovery. The hepatitis-C virus is similarly carcinogenic. Approximately one-fifth of all human cancers worldwide arise in the stomach, liver, or cervix, and most of these cancers would be prevented if these infections could be eradicated.

6) Other pathogens that cause a substantial cancer risk in certain populations include Epstein-Barr virus (various B-cell malignancies and nasopharyngeal cancer), malaria (Burkitt's lymphoma), human T-cell lymphotropic virus type I (some T-cell leukemias and lymphomas), HIV (non-Hodgkin's lymphoma), human herpesvirus 8 (Kaposi's sarcoma, with HIV), schistosomiasis (bladder and colon cancer), liver flukes (cholangiosarcoma). There is also strong epidemiological evidence for an infective etiology in childhood leukemia, but no specific pathogen has been implicated. The incidence of several virally induced cancers is further increased by specific cofactors such as dietary aflatoxin (liver cancer), salted fish (nasopharyngeal cancer), and smoking (liver and cervical cancer).

7) Tobacco causes one-third of all cancer deaths in developed countries. Approximately 15 percent of cancers worldwide re caused by known infectious agents. Hepatitis-B virus alone causes almost as many cancers as smoking in China, and can be prevented by vaccination. Human papilloma virus vaccines that are already being tested may be able to prevent almost all cervical cancers, and if the prevalence of Helicobacter pylori can be reduced, many stomach cancers would be avoided. The belated elimination of asbestos by many Western countries will eventually prevent the great majority of mesotheliomas and many lung cancers. Various cancer screening tests are partially effective, and cervical cancer screening is very effective.

Julian Peto: Cancer epidemiology in the last century and the next decade.

Nature 2001 411:390

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