MicroBio 160 1st Edition Lecture 9Outline of Last Lecture I. What is Epidemiology?II. The Epidemiological ApproachIII. Epidemiological StudyIV. How do we Evaluate Evidence V. Comparison of Disease in Different Locations VI. What’s the Difference?VII. The Effect of BiasVIII. Limitations of EpidemiologyIX. Types of EpidemiologyX. The Epidemiologic TriadXI. Main Causes of CancerOutline of Current Lecture I. Cancer Cases and Risk FactorsII. The Ames Test for Carcinogenic Potential III. Environment vs. HereditaryIV. Diet and Cancer RiskV. Radiation and CancerVI. Oncogenic Viruses and BacteriaVII. How Do You Know if You Are At Risk?VIII. Somatic vs. Inherited CancersIX. Hereditary Risk ExamplesX. Typical Xeroderma Pigmentosum PedigreeXI. Familial Retinoblastoma PedigreeCurrent LectureCancer Cases and Risk Factors:- Age- Environmental Factors - Lifestyle Factorso Tobacco Use o Alcohol use o Diet/ food- RadiationThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.- Oncogenic Viruses (viruses that trigger oncogenes)—insert their DNA into our DNA and cause mutations which can cause cancer- HereditaryThe Ames Tests for Carcinogenic Potential:- Mutagenic: able to cause a mutationo A mutagenic isn’t necessarily a carcinogenic- Carcinogenic: able to cause cancer- Take substance you want tested - -liquid form- - combine substance being tested with liver homogenate- - incubate them- - but bacteria on 2 different growth mediums - - take mutigen and add it to one of the plates- -add bacteria and wait to see what grows63% of risk is in your own controlIf mutagenic, then may randomly create a mutation that restores histidine synthesis- Take substance you want tested (liquid form)- Combine substance being tested with liver homogenate- Incubate them- Put bacteria on 2 different growth mediums -Take mutigen and add it to oneof the platesEnvironment vs. Hereditary:- Study of people that move from 1country to another - Hereditary stays the same, environment changeso In Japan, stomach cancer high, colon cancer lowo Opposite is true in USA- Japanese immigrants move to USAo Differences begin to disappearo Children of immigrants acquire cancer risks of new location- Thus environment plays a larger role than hereditaryo 80-90% of cancer risk due to environmento 10-20% due to hereditary If it were strictly genetic, kids would get the same ones as their parents even if they changed environments Some inherited mutations increase the risk of developing cancer to almost 100%Diet and Cancer Risks:Bottom Left: 2 bacterium out of 100s that gained a mutation Right: a lot of colonies-- more growth-acquired the ability to make the histidine-- original substance causes mutations- Large amount to small amount (x axis)- If it takes 100 then it is less immunogenic (large dose, weakly carcinogenic, mutagenic)Top Right: highly immunogenic, mutagenic-- really high risk of developing cancer- All about where the mutationsRadiation and Cancer:- Gamma Rays and X rays—ionizing radiation is high frequency radiation with enough energy to remove an electron from an ion (ionize) or molecule. o Ionizing radiation has enough energy to damage the DNA in cells, which inturn may lead to cancer- Ultraviolet Rays (UV)—high energy UV damages DNA, whereas low energy UV does not- Visible light, infrared rays, microwaves, radiofrequency (radio) waves, extremely low frequency radiation (ELF)Oncogenic Viruses and Bacteria:- EBV—Burkitts’s Lymphoma- Hepatitis B—Liver cancer- HPV—Cervical cancer- H. Pylori—Stomach cancero H pylori- causes stomach ulserso Stomach secretes Hydrochloric acido Can dissolve all foods you are eatingo Stomach secretes mucus to keep away h pyloriHereditary and Cancer:Foods contain carcinogens and anti-carcinoogens- Anti-carcinogens in fruits may block carcinogensEpidemiologists estimate that diets play a role in ~30% of allfatal cancers- US higher with cancer rates and meat consumption- Different foods have different carcinogensHow do you know if you are at risk?- A family history that might indicate an inherited gene mutation would include two or more of the following points:o Cancer in several closely related people, on the same side of the family, and in several generationso Cancer at younger ages than usual (breast cancer in your 30’s)o More than one diagnosis of cancer in the same persono Specific types of cancer that are linked to specific genes (breast cancer and ovary cancer or colon cancer and endometrial cancer)Somatic vs. Inherited Cancers:- Most often used DNA repair genes- There is a risk of getting breast cancer with ageHereditary Risk Examples:- Recessive risk- takes two bad copies of a geneo Not every person will get ito It knocks out DNA repair gene - Genes affecting DNA repairo Xeroderma Pigmentosum- Genes involved in Tumor Suppressoro RetinoblastomaSomatic mutations occur after conception- No mutation is present—embryo starting to develop mutation - Occur in any of the cells of the body (somatic) except the germ cells (sperm and egg)—thus, they are not passed onto childrenInherited Mutations occur before conception- Occur in the germ cells (sperm and egg)— thus are passed onto children- Every cell in that organism will have that mutation- Can cause cancer or other diseasesTypical Xeroderma Pigmentosum Pedigree- Requires 2 copies of mutant gene to be inherited, one from each parent (recessive cancer risk syndrome)o Must have one normal gene to make the protein (DNA repair gene)o Results in absence of DNA repairo Carriers exhibit no disease symptoms, but can pass gene on to childreno Each child will have a 50% chance of inheriting mutant gene from each parent (overall probability is 50% x 50%= 25%)- Patients are sensitive to UV—sunlight could be fatalo Suit designed by NASAo Minimal sunlight exposure leads to skin cancero Camp Sundown in upstate NY allows kids to participate in normal recreation indoorsFamilial Retinoblastoma Pedigree (eye cancer)- Red= developed retinoblastoma- Green symbol= no signs of disease- Yellow arrow= son with no disease, but children inherited disease.o Represents the 10% that inherit but do not develop disease (incomplete penetrance)- A non-carrier child has a 1 in 20,000 chance of developing retinoblastoma- In families of retinoblastoma survivors, ~50% of the children develop the disease- ~40% of retinoblastoma cases are
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