Therapeutic irradiation of the head and neck can give rise to papillary thyroid cancers years later. The oncogenic properties of ionizing radiation are related to its mutagenic effects; it causes chromosome breakage, chromosomal rearrangements such as translocations and inversions, and, less frequently, point mutations. Biologically, double-stranded DNA breaks seem to be the most important form of DNA damage caused by radiation.
The oncogenic effect of UV rays merits special mention because it highlights the importance of DNA repair in carcinogenesis. Natural UV radiation derived from the sun can cause skin cancers (melanomas, squamous cell carcinomas, and basal cell carcinomas). At greatest risk are fair-skinned people who live in locales such as Australia and New Zealand that receive a great deal of sunlight. Nonmelanoma skin cancers are associated with total cumulative exposure to UV radiation, whereas melanomas are associated with intense intermittent exposure—as occurs with sunbathing. UV light has several biologic effects on cells. Of particular relevance to carcinogenesis is the ability to damage DNA by forming pyrimidine dimers. This type of DNA damage is repaired by the nucleotide excision repair pathway. With extensive exposure to UV light, the repair systems may be overwhelmed, and skin cancer results. As mentioned earlier, patients with the inherited disease xeroderma pigmentosum have a defect in the nucleotide excision repair pathway. As expected, there is a greatly increased predisposition to skin cancers in this disorder.
Ionizingradiationcauseschromosomebreakage,chromosomerearrangements,and,lessfrequently,pointmutations,anyofwhichmayaffectcancergenesandtherebydrivecarcinogenesis.
UVraysinsunlightinducetheformationofpyrimidinedimerswithinDNA,leadingtomutationsthatcangiverisetosquamouscellcarcinomasandmelanomasoftheskin.
Many DNA and RNA viruses have proved to be oncogenic in animals as disparate as frogs and primates. Despite intense scrutiny, however, only a few viruses have been linked with human cancer. The following discussion focuses on human oncogenic viruses. Also discussed is the role of the bacterium Helicobacter pylori in gastric cancer.
Although the study of animal retroviruses has provided spectacular insights into the molecular basis of cancer, only one human retrovirus, human T-cell leukemia virus type 1 (HTLV-1), is firmly implicated in the pathogenesis of cancer in humans.
HTLV-1 causes adult T-cell leukemia/lymphoma (ATLL), a tumor that is endemic in certain parts of Japan, the Caribbean basin, South America, and Africa, and found sporadically elsewhere, including the United States. Worldwide, it is estimated that 15 to 20 million people are infected with HTLV-1. Similar to the human immunodeficiency virus, which causes AIDS, HTLV-1 has tropism for CD4+ T cells, and hence this subset of T cells is the major target for neoplastic transformation. Human infection requires transmission of infected T cells via sexual intercourse, blood products, or breastfeeding. Leukemia develops in only 3% to 5% of the infected individuals, typically after a long latent period of 40 to 60 years.