Conference paper
Genetical Factors and Infectious Agents in the Aetiology of Cancer
Krešimir Pavelić
; Ruđer Bošković Institute
Abstract
Although many of the specific physiological and genetic mechanisms by which environmental carcinogens cause cancer remain elusive, scientists now have a good sense of the extent to which various categories of agents contribute to lethal cancer. Two gene classes, which together constitute only a small proportion of the full genetic set, play major roles in triggering cancer. In their normal configuration, they choreograph the life cycle of the cell – the intricate sequence of events by which a cell enlarges and divides. Protooncogenes encourage such growth, whereas tumour suppressor genes inhibit it. When mutated, protooncogenes can become carcinogenic oncogenes that drive excessive cell multiplication. Tumour suppressor genes, in contrast, contribute to cancer when they are inactivated by mutations. The resulting loss of functional suppressor proteins deprives the cell of crucial brakes that prevent inappropriate growth. Cancer arises when a single cell accumulates a number of these mutations, usually over many years, and finally escapes from most restraints on proliferation. The mutations allow the cell and its descendants to develop additional alterations and to accumulate in increasingly large numbers, forming a tumour that consists mostly of abnormal cells. Many cancer types exhibit familial clustering, suggestive of a significant inherited component. However, to date only a few of the responsible genes have been identified and the inherited component underlying the most common cancers has not been well defined. Among the important known susceptibility genes are those dominant genes conferring a high risk of breast and ovarian cancer, colon cancer, and melanoma. All these genes confer a high lifetime risk of disease, but are rare and account for a small minority (less than 5%) of cases. Important factors in molecular carcinogenesis are viruses, bacteria, and parasites. Perhaps as many as 15% of the world’s cancer deaths can be traced to them. The most common cancer-causing pathogens are the DNA viruses which propagate by invading the living cells of a host and using the cell’s DNA-synthesizing and protein making machinery to generate copies of themselves. Of these carcinogenic agents the most important is human papillomavirus (HPV) type 16 and 18 and hepatitis B virus. Other viruses have also been found to cause various kinds of cancer such as Epstein Barr which produces mononucleosis and HIV producing Kaposi’s sarcoma and lymphoma. Helicobacter pylori, the only bacterium linked to cancer is strongly associated with the occurrence of stomach cancer. It still remains to be determined why these pathogens give rise to cancer in some infected people but not in others. Although the epidemiological evidence linking infection with some infective agents to malignancies is generally convincing, experimental systems indicated a clear role only for some of the HPV encoded genes in the tumour cell growth. A detailed understanding of the molecular mechanism of oncogenesis will be required to design drugs for the treatment of these cancers. Prophylactic vaccination resulting in prevention of infection may be an effective approach to reduce the incidence of some cancers.
Keywords
malignant tumours; oncogenes; tumour suppressor genes; viruses
Hrčak ID:
65645
URI
Publication date:
26.7.2000.
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