Cancer progresses through accumulation of multiple mutations Each successive mutation allows those cells to proliferate more quickly than those around it.

Cancer is a genetic disease, but not usually inherited. Most cells in the body are somatic cells. Most mutations are in the somatic cells. Germline mutations are inherited by offspring

…but it sometimes is inherited and runs in families. Each cell has 2 copies of each tumor suppressor gene. Both copies must be mutated for cancer to form. If first mutation is inherited, all cells are susceptible to 2nd mutation.

2-hits in retinoblastoma Cancer of the retina Small tissue with only one tumor suppressor gene active. Most people get only 1 mutation in any given cell No cancer Some people get 2 mutations in any given cell Cancer in one eye Some people inherit mutation in all of their cells. Next mutation causes cancer. Cancer in both eyes usually by age 5.

What causes mutations to occur and spread? Mutations may be inherited Carcinogens – any agent involved in the promotion of cancer Smoke (esp. cigarette smoke) Radiation / sun Chemicals / solvents Infectious diseases (eg Human papillomavirus) Food (esp. charred meat) Hormones (eg. Estrogen) Many, many others!

External signals that control cell proliferation: growth factors

External signals that control cell proliferation

Cell proliferation: tumors recruit blood vessels to supply oxygen and nutrients. Tumors secrete Growth factors that promote angiogenesis (formation of blood vessels

Tumor growth 2nd mutation increases growth rate and changes appearance of cells First mutation causes rapid growth After recruiting blood supply, may metastasize to other tissues

Risk Factors Family history Tobacco use Smokeless tobacco Diet But only 5% of cancers are inherited Tobacco use 30% of all cancers and 87% of lung cancer Smokeless tobacco Oral and pancreatic cancers Diet Eat fruits and vegetables Avoid charred meats Avoid preserved meats

Risk factors Being sedentary Alcohol Irregular medical care Moving helps push food through your intestines, limiting exposure to carcinogens Alcohol Irregular medical care Cancer goes undetected Sunlight (UV and other radiation) Chemical carcinogen exposure Infectious agents (eg. HPV for cervical cancer)

Treatment options Surgery Removal of cancerous tissue Radiation Kills cancer cells (usually targeted to specific tissue) Chemotherapy Uses chemicals to kill cancer cells (throughout body) Biological immunotherapy Strengthens immune system Transplants Particularly Bone Marrow for leukemias