The Genetics of Cancer Cancer: a group of 100 or more disorders that arise from alterations in genes; predominantly in somatic cells; 1 in 3 persons; from translocations, aneuploidy, chromosomal deletions, chromosomal loss Cell divides out of control Growth called tumor – Benign (grows in place/does not spread) vs. Malignant (infiltrate nearby tissue – metastasis)  More than 100 oncogenes cause cancer when activated  30 tumor suppressor genes – deletion or activation causes cancer  Cancer cells with long telomeres (telomerase turned on)  Sporadic Cancer: in somatic cells (isolated)  Germline Cancer: in gametes (passed on); rare; strike earlier in life; 1-2%; 1% of colon cancer cases result from genetic disposition to cancer known as Familial Adenomatous Polyposis (produce clusters of cells called polyps)

Clonal Origin: cell originated from a common ancestral cell that accumulated specific mutation Viruses: 2 nd genetic risk factor for cancer Tobacco smoke with 60 different chemicals that interact with DNA and cause mutations Cell Cycle: Cancer cells unable to enter G0 receives continuous growth signals 3 points in cycle where cell monitors signals and equilibrium (G1/S, G2/M, and M) abnormal regulation leads to cancer; proteins (cyclins and cyclin-dependent kinases) control progress cell destroys cyclin proteins

Characteristics of Cancer Cells Rounder; heritable; transplantable; dedifferentiated; ability to spread (metastasis); invasive (“tentacles”); loss of contact inhibition; ability to induce local blood vessel formation (angiogenesis) Divide continuously Cervical cancer cells of Henrietta Lacks (1951) HeLa cells (standard cultures in research labs)

Genes That Cause Cancer Oncogenes Ras Proto-oncogenes normally trigger cell division mutation oncogenes Viruses changes proto- oncogenes into oncogenes (Kaposi Sarcoma, Acute T cell leukemia); 15% of human cancers Fusion protein: oncogene activates when proto-oncogene moves next to another gene (translated together) Tumor Suppressors: cancer from the loss of a gene that normally suppresses tumor formation Cells lacking p53 unable to arrest cell cycle checkpoints or enter apoptosis; most frequently mutated gene in cancers Retinoblastoma (RB1): deletions in the long arm of chromosome 13; 1 in 15,000 persons BRCA1 (breast cancer predisposition gene): 2 adjacent bases deleted, altering the reading frame and shortening the protein

Apoptosis Cell commits suicide Initiated during normal multicellular development in order to eliminate certain cells that do not contribute to the final adult organism (sculpting) Example: fingers and toes carved from webbed structures Death receptor on cell membrane receives a signal to die Caspases (enzymes) snip apart cell components Cancer: apoptosis occurs too infrequently Abnormality: webbing (syndactyly)

Apoptosis

Cancer Prevention Avoid high-risk environmental factors (excessive sun exposure) Diet: cruciferous vegetables (broccoli, Brussels sprouts) with decreased rate of colon cancer Produce glucosinolates activate xenobiotic metabolizing enzymes detoxify carcinogenic products of cooked meat Red meat: connection to colon, prostate and breast cancer Alcohol: connection to liver cancer Chemoprevention: taking certain nutrients, plant extracts, or drugs to lower the risk of cancer Folic acid, vitamins D and E, selenium, compounds from soybean, tomatoes, green tea Avoid Aflatoxin – component of a mold that grows on peanuts and corn (one of the most carcinogenic) Avoid Nitrosamines – chemical carcinogens from synthetic substances in preserved meat

Cancer Studies Population Study: compares the incidence of a type of cancer among very different groups of people Case-Control Study: people with a type of cancer are matched with healthy individuals for age, sex, and other characteristics Prospective Study: 2 or more groups of people follow a specified dietary regimen and are checked periodically for cancer Treatment Surgery Radiation and chemotherapy New Drugs (Avastin)