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• What is Cancer? – Cancer develops when cells in a part of the body begin to grow out of control. Although there are many kinds of cancer, they all start because of out-of-control growth of abnormal cells. – Normal body cells grow, divide, and die in an orderly fashion. During the early years of a persons life, normal cells divide more rapidly until the person becomes an adult. After that, cells in most parts of the body divide only to replace worn-out or dying cells and to repair injuries. – Because cancer cells continue to grow and divide, they are different from normal cells. Instead of dying, they outlive normal cells and continue to form new abnormal cells. – Cancer cells develop because of damage to DNA. This substance is in every cell and directs all its activities. Most of the time when DNA becomes damaged the body is able to repair it. In cancer cells, the damaged DNA is not repaired. People can inherit damaged DNA, which accounts for inherited cancers. Many times though, a person’s DNA becomes damaged by exposure to something in the environment, like smoking. • Source - ACS
Rate Per 100,000100 80 Cancer Death Rates, for Women 60 Lung Uterus Breast 40 Colon & rectum Stomach 20 Ovary Pancreas 0 1935 1945 1950 1960 1965 1970 1975 1980 1985 1990 1995 2000 1930 1940 1955 *Age-adjusted to the 2000 US standard population. Source: US Mortality Public Use Data Tapes 1960-2000, US Mortality Volumes 1930-1959, National Center for Health Statistics, Centers for Disease Control and Prevention, 2003.
Lifetime Probability of Developing Cancer,Men, US, 1998-2000 Cance r All sites 1 in 2 Source: DevCan: Probability of Developing or Dying of Cancer Software, Version 5.1 Statistical Research and Applications Branch, NCI, 2003. http://srab.cancer.gov/devcan
• What is the molecular basis of cancer? – Cancer is a genetic disease. • Mutations in genes result in altered proteins – During cell division – External agents – Random event • Most cancers result from mutations in somatic cells • Some cancers are caused by mutations in germline cells
• Theories of cancer genesis – Standard Dogma • Proto-oncogenes (Ras – melanoma) • Tumor suppressor genes (p53 – various cancers) – Modified Dogma • Mutation in a DNA repair gene leads to the accumulation of unrepaired mutations (Loeb, 1974) (xeroderma pigmentosum) – Early-Instability Theory • Master genes required for adequate cell reproduction are disabled, resulting in aneuploidy (Philadelphia chromosome)
• Problem posing – Can we understand the mechanism(s) of cancer by examining the expression patterns of genes in the cancer cell? – Can we use gene expression patterns to determine the properties of a cancer? –