Harrison's Internal Medicine Chapter 79. Cancer Genetics Cancer Is a Genetic Disease Cancer arises through a series of somatic alterations in DNA that result in unrestrained cellular proliferation. Most of these alterations involve actual sequence changes in DNA (., mutations). They may arise as a consequence of random replication errors, exposure to carcinogens (., radiation), or faulty DNA repair processes. While most cancers arise sporadically, familial clustering of cancers occurs in certain families that carry a germline mutation in a cancer gene. Historical Perspective The idea that cancer progression is driven by sequential somatic mutations in specific genes has only gained general. | Chapter 079. Cancer Genetics Part 1 Harrison s Internal Medicine Chapter 79. Cancer Genetics Cancer Is a Genetic Disease Cancer arises through a series of somatic alterations in DNA that result in unrestrained cellular proliferation. Most of these alterations involve actual sequence changes in DNA . mutations . They may arise as a consequence of random replication errors exposure to carcinogens . radiation or faulty DNA repair processes. While most cancers arise sporadically familial clustering of cancers occurs in certain families that carry a germline mutation in a cancer gene. Historical Perspective The idea that cancer progression is driven by sequential somatic mutations in specific genes has only gained general acceptance in the past 25 years. Before the advent of the microscope cancer was believed to be composed of aggregates of mucus or other noncellular matter. By the middle of the nineteenth century it became clear that tumors were masses of cells and that these cells arose from the normal cells of the tissue in which the cancer originated. However the molecular basis for the uncontrolled proliferation of cancer cells was to remain a mystery for another century. During that time a number of theories for the origin of cancer were postulated. The great biochemist Otto Warburg proposed the combustion theory of cancer which stipulated that cancer was due to abnormal oxygen metabolism while normal cells required oxygen cancer cells could survive in its absence. In addition some believed that all cancers were caused by viruses and that cancer was in fact a contagious disease. In the end observations of cancer occurring in chimney sweeps studies of x-rays and the overwhelming data demonstrating cigarette smoke as a causative agent in lung cancer together with Ames s work on chemical mutagenesis were sufficient to convince many that cancer originated through changes in DNA. Although the viral theory of cancer did not prove to be generally accurate the study
