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1.1 PERSPECTIVE AND HISTORY
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It is recognized increasingly that cancer is a genetic disease that occurs because of mutations in critical (driver) genes and that the development of a cancer, especially in adults, is often a long process taking many years. Epidemiologic studies have identified many environmental factors that can cause mutations and are carcinogenic. When Sir Percival Pott carried out his epidemiologic study in 1775, suggesting that the causative agent of scrotal cancer in young chimney sweeps might be chimney soot (now known to be tar), he not only identified the putative carcinogenic agent but also demonstrated that a cancer may develop years after exposure. Another dramatic example is mesothelioma, which is a rare cancer arising from the pleural membranes around the lungs, that develops decades after exposure to asbestos (Lemen, 2016). Epidemiologic studies have also identified tobacco smoke as a major environmental cause of several types of cancer: Doll and Hill (1950) showed that heavy smokers over the age of 50 have a 1 in 2 chance of dying from a smoking-related disease such as lung cancer. On the positive side, individuals who quit smoking at an early age exhibit a gradual return to a near-normal risk of lung cancer (Doll et al, 2004). More recently, obesity (which is increasingly a health concern throughout the world) has been associated with increased risk of certain types of cancer (eg, breast, colorectal), and reducing weight is associated with a lower cancer risk (Iyengar et al, 2015; Hopkins et al, 2016). These and other studies underscore the possibility that, with some types of cancer, a degree of prevention may be achieved via changes in lifestyle.
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Other historically important contributions to the understanding of cancer include an appreciation that cancer is, in part, heritable. Studies of geographically or socially isolated populations, such as the Mormons in Utah, and of changes in cancer incidence in migrant families demonstrated that both genetic predisposition and environmental factors are important in cancer causation. Analysis of cancer-prone families have assisted in the identification of genetic abnormalities that can lead directly to malignancy, such as mutation of tumor suppressor genes, including the retinoblastoma gene (RB) in children, the TP53 gene in Li-Fraumeni syndrome, and the BRCA1 and BRCA2 genes, which are associated with familial breast and ovarian cancer. Viruses have also been identified as causative in the development of some common human cancers, including hepatitis viruses (B and C) as precursors of hepatocellular carcinoma, and human papilloma viruses (HPVs) as a causative agent for a range of cancers including those of the cervix and the oropharynx. The development of vaccines against HPV (Future II Study Group, 2007) and of vaccination programs against hepatitis B virus (HBV) and hepatitis C virus (HCV) in regions where these viruses are endemic (Luo and Ruan, 2012) holds promise for marked reduction in the incidence of these cancers.
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