Chapter 12 Genes and Cancer

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Cancer
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a complex disease affecting many different cells and tissues — uncontrolled cell division –the ability of the cells to spread to other sites in the body
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benign tumors
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noncancerous tumor, does not spread beyond place of origin. Encapsulated by a tissue
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malignant tumors
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breaks away and moves to other locations
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all cancers start as a
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genetic mutation
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most of the time cancer is in what cells?
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somatic
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cancer in germ cells
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1% occurance passed on to offspring only predisposition to cancer
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4 nucleotide changes
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substitutions deletions additions chromosome rearrangements (gain or loss)
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3 spontaneous carcinogens due to environment
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UV Light chemicals viruses
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2 types of chemical carcinogens
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Industrial- made recreational- drugs (heroin, alcohol, etc.)
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spontaneous behavior carcinogens
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diet smoking
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turmors are
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abnormal growth
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Cancer begins in
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a single cell
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most cancers develop after…
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a cell accumulates a number of specific mutations over a long period of time
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cancer cells…
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divide continuously and are invasive
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3 reasons for cancer
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inheritance chance environmental agents
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inheritance of cancer
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inherit a mutant gene which causes predisposition to cancer individual will carry mutant gene in germ cells and all somatic cells if one or more additional mutations accumulate spontaneously or as a result of exposure to mutagenic environmental agens in any somatic cell, the result is cancer
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sporadic cases of cancer
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most common form of cancer single dominant mutation occurs in a somatic cell somatic cell quires a certain number of recessive mutations– 2 min.
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Cancer cells characterized by
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uncontrolled cell cycle abnormal shapes
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cancer occurs where in the cell cycle?
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Interphase mitosis and cytokinesis
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regulation of cancer in the cell cycle (checkpoints)
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G1 before the S phase between G2 and M mutations in the genes that suppress these checkpoints are important in cancer development –cancer cells bypass these checkpoints
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tumor supressor genes
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genes that turn off or decrease the rate of cell division –if the genes mutate or are inactivated cells pass through the checkpoint and divide in an uncontrolled manner
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proto-oncogenes
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encode proteins that are important for cell growth and division –when a cell stops dividing it turns off the proto-oncogene –left on in cancer cells
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oncogenes
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genes that cause cancer by blocking the normal controls on cell reproduction
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retinoblastoma
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caused by a mutation of a tumor suppressor gene affects the retina 1 in 14,000/20,000 diagnosed between ages 1-3
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2 forms of retinoblastoma
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familial retinoblastoma Sporadic retinoblastoma
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familial Retinoblastoma
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individuals inherit 1 mutant copy of RB1 85-90% chance of developing cancer, usually in both eyes at high risk of bone, lung, and bladder cancers
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sporadic Retinoblastoma
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mutations in both copies of RB1 occur in a sinlge retinal cell tumors develop in only 1 eye not at high risk for other cancers mutations confined to the tumor
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RB1
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chromosome 13q14 makes a suppressor protein pRB
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pRB
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if active during G1 the cell will not move into the S phase if not active during G1 the cell will move nto the S phase through G2 and into mitosis if both copies are mutated, there is no regulation of cell division, uncontrolled cell division forming a tumor
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proto-oncogene mutation
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causes cancer a single base mutation can cause production of an altered gene product, mutations of under/over production of gene product, and an an increased number of copies of a normal gene
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difference between proto-oncogenes in normal cells and mutant oncogenes in cancer cells
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a single base change
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change of glycene to valine
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changes the protein into an active state, constantly growing
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Cancer properties
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higher rates of mutation abnormal chromosome structure and number
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geonomic instability
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loss of ability to repair DNA inc ancerous cells
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Breast cancer
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most common cancer for women in US 40,000 Die/year predisposition to breast and ovarian cancer mutations in 2 genes
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Breast cancer mutation
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BRCA1 and BRCA2
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BRCA1
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chromosome 17q responsible for breast cancer in women under 40 1 in 200 women have mutant gene, 80% will develop cancer marker for ovarian cancer close to 17q –higher risk of ovarian cancer showed autosomal dominantly inherited predisposition to breast cancer 50% of a ll inherited cases are due to this mutation
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BRCA2
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chromosome 13q together with BRCA1 account for 2/3 of all breast cancer women of european Jewish descent are at highest levels 2.5%
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BRCA1 and BRCA2
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DNA repair genes
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DNA repair genes
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if DNA is damaged, BRCA1 gene is activated this will cause DNA to stop DNA replication until repair is done if BRCA1 has a mutation the gene will not be activated –Results in no repair of double stranded breaks in DNA molecules
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Colon/rectal cancer
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one of the most common forms of cancer in US autosomal dominant developement of this cancer is caused by 5-7 mutations
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polyps
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benign colon tumors 1st step in colon cancer
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FAP
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related to colon cancer APC gene is first mutation located on chromosome 5q also 12, 17, 18 chromosomes –triggers mutations in several tumor suppressor genes causing transition from polyps to cancer
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HNPCC
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does not form polyps the MSH2 or MLH1 are genes affected by autosomal dominant mutations causes microsatellites to form
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microsatellites
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repetition of DNA sequences 1000s of times 2-9 nucleotides long
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gatekeeper genes
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control the cell cycle mutations cause uncontrolled cell division tumor suppressor genes and proto-oncogenes
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caretaker genes
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repair DNA errors mutations in caretaker genes increases the mutation rate in all genes
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Common causes of cancer
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change in structure and number of chromosomes
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Down Syndrome
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18-20x more likely to get leukemia
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leukemia
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uncontrollable division of WBCs caused by a translocation between chromosomes 9 and 22 causes the CML cells to constantly divide
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traditional treatment of cancer
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radiation and chemicals target rapidly dividing cells
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Cancer treatment
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diagnostic tests test for mutant protein in the bloodstream- breast and prostate cancers research is being done to find ways to turn off oncogene expression designer drugs treat specific cancers without side effects
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Epidemiology
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the study of factors that control the presence or absence of a disease finding correlations between environmental agents and the existence of a disease study cancer in several different populations
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tobacco and cancer
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smoking= 85% of lung cancer in males, 75% in women contributes to oral cavity, larynx, esophagus, and lung cancer 30% if cancer deaths snuff/chew increases risk of oral cancer by 50%
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Skin cancer
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1 mill new cases a year most common form of cancer caused by UV light and tanning beds genetic characteristics affect susceptibility of people and population to environmental agents that cause cancer
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3 causes of increased skin cancer
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ozone depletion= increased levels of UV radiation more outdoor activity attitude that suntans are healthy

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