neoplasia

• Neoplasia


  The formation of new and abnormal growth of tissue
• In 2008, it was estimated that there were about 12.7 million new cancer cases worldwide, leading to 7.6million deaths (21,000 deaths per day)
• Due to increasing population size and age, by 2030 it is projected that the number of cancer cases and cancer ­related deaths worldwide will increase to 21.4 million and 13.2 million, respectively
• Cancer is ubiquitous in human populations; the only certain way to avoid cancer is to not be born, as to live is to incur risk
• There is remarkable geographic variation in the incidence of specific cancers that is believed to stem mainly from differences in exposure to environmental carcinogens suggesting that many (and perhaps even most) cancers are preventable
• Most common tumors in men

  • Prostate
  • Lung
  • Colon/rectum
• Most common tumors in women

  • Breast
  • Lung
  • Colon/rectum
• Cancers of the lung, female breast, prostate, and colon/ rectum constitute more than 50% of cancer diagnoses and cancer deaths in the United States
• In the developing world the most common cancers involve the lung, stomach, and liver in men and the breast, cervix, and lung in women
• Most longitudinal data pertaining to cancer incidence comes from developed countries
• In the last 50 years of the twentieth century, the overall age-adjusted cancer death rate increased significantly in both men and women in the United States
• In the United States, the cancer incidence rate has been stable since 1995 and the cancer death rate has decreased
• The last half-century has seen a sharp decline in the number of deaths caused by cervical cancer in the US, which is attributable to the Papanicolaou (Pap) smear test, which enables detection of precursor lesions and early, curable cancers
• African Americans had the largest decline in cancer mortality during the past decade
• Hispanics living in the United States have a lower frequency of the most common tumors seen in the white non-Hispanic population but a higher incidence of tumors of the stomach, liver, uterine cervix, and gallbladder, as well as certain leukemias
• Environmental influences appear to be the dominant risk factors for most cancers
• Environmental factors contributing to cancer

  • Infectious agents (about 15% of all cancers worldwide)
  • Smoking (particularly cigarettes, implicated in about 90% of lung cancer deaths)
  • Alcohol consumption
  • Diet
  • Obesity
  • Reproductive history
  • Environmental carcinogens
• Occupational cancers are caused by environmental factors in the workplace
• Age


  Most carcinomas occur in the later years of life (>55 years), cancer is the main cause of death among women aged 40 to 79 and among men aged 60 to 79, the decline in deaths after age 80 is due to the lower number of individuals who reach this age
• Cancer accounts for slightly more than 10% of all deaths in children younger than age 15 in the United States, second only to accidents
• Common neoplasms of infancy and childhood

  • Neuroblastoma
  • Wilms tumor
  • Retinoblastoma
  • Acute leukemias
  • Rhabdomyosarcomas
• Acquired conditions that predispose to cancer

  • Chronic inflammations
  • Precursor lesions
  • Immunodeficiency states
• Repeated rounds of cell division may be required for neoplastic transformation, in that proliferating cells are the most at risk for accumulating the genetic lesions that lead to carcinogenesis
• Tumors arising in the context of chronic inflammation are mostly carcinomas, but also include mesothelioma and several kinds of lymphoma
• Patients who are immunodeficient, and particularly those who have deficits in T-cell immunity, are at increased risk for cancers, especially those caused by oncogenic viruses
• Chronic inflammation and cancer

  A cause-and-effect relationship between chronic inflammation and cancer was first proposed by Virchow in 1863, and it is now appreciated that cancer risk is increased in individuals affected by a variety of chronic inflammatory diseases, including those with infectious and noninfectious etiologies
• Chronic epithelial injury often leads to metaplasia, the replacement of one cell type with a second that is better able to survive the ongoing insult
• Diagnosis and effective treatment of Helicobacter pylori gastritis with antibiotics can quell a chronic inflammatory condition that might otherwise lead to the development of a gastric cancer
• Precursor lesion


  Entities that are associated with increased cancer risk, but do not inevitably progress to cancer
• Examples of precursor lesions

  • Barrett esophagus
  • Squamous metaplasia of the bronchial mucosa
  • Squamous metaplasia of the bladder mucosa
  • Colonic metaplasia of the stomach
  • Endometrial hyperplasia
  • Leukoplakia
  • Colonic villous adenoma
• Benign tumors at high risk for malignant transformation possess the cancer-enabling property of genomic instability, whereas truly benign tumors do not
• Genetic Predisposition and Interactions Between Environmental and Inherited Factors

  In some families cancer is an inherited trait, usually due to germ-line mutations in a tumor suppressor gene, but the risk of developing the tumor can be greatly influenced by non-genetic factors
• Inherited variations (polymorphisms) of enzymes that metabolize procarcinogens to their active carcinogenic forms can influence cancer susceptibility
• Carcinogenesis


  Cancers result from the stepwise accumulation of multiple mutations that act in complementary ways to produce a fully malignant tumor
• More than 200 years ago the London surgeon Sir Percival Pott correctly attributed scrotal skin cancer in chimney sweeps to chronic exposure to soot, and the Danish Chimney Sweeps Guild ruled that its members must bathe daily
• Chemical carcinogenesis


  Initiation - results from exposure of cells to a sufficient dose of a carcinogenic agent, causing permanent DNA damage

  Promotion - can induce tumors to arise from initiated cells, but are non-tumorigenic by themselves
• Cure since that time has achieved so much in controlling a form of cancer!
• Hundreds of chemicals have been shown to be carcinogenic in animals
• Carcinogenesis


  A multistep process
• Chemical carcinogenesis


  1. Initiation

  2. Promotion