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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

answer

ozone depletion= increased levels of UV radiation more outdoor activity attitude that suntans are healthy

Chapter 12 Genes and Cancer – Flashcards

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