Lecture 13 - Cancer Epidemiology Flashcards
Review Table 13-1 paying particular notice of the carcinogenic agents that have been
implicated in causing cancer in humans.
Tobacco (60 carcinogens) Creosotes (from tars = wood/fossil fuel) Nitrosamines Benzene Hair Dyes Pesticides Petrochemicals (car exhaust) Toluene
Summarize the role of epigenetics in cancer transformation. From the 7 changes listed in chapter 12, delineate which of those could be attributed to gene silencing, and which could
be a result of inappropriate un-silencing of dormant genes.
Role of epigenetics: silences genes by methylation or deacetylation
- 1 mutation in an oncogene (responds abnormally to growth factors) –> can be GF or receptor or signal cascade to nucleus (RAS mutation) that signals cell to grow in the absence of GF
- 2 mutations in Tumor Suppressor Gene –> two mutations in each homologous gene or epigenetic suppression or gene deletion
- Mutation in genes regulating glycosphingolipids (increased responsiveness to GF)
- Mutation disabling the apoptosis process, usually P53 gene
- Mutation or alteration in genes expressing telomerase
- Mutation in genes involved with the expression of fibronectin
- Mutation of genes making or regulating gap junctions
- abnormal secretion of angiogenic GF
In light of the fact that only 24% of women with the BRCA1 or BRCA2 mutation born before 1940 develop cancer by the age of 50 while 67% of women born after 1940 with the same inherited mutations develop breast cancer before the age of 50, describe other factors that might be more prevalent now than before 1940 which could explain the increase rate of
carcinogenesis.
Factors more prevalent now that before in women that can cause carcinogenesis is supplemental estrogen and progesterone. Women who go into menopause will be prescribed this to help with the discomfort of hot flashes, etc.
Identify the five types of viruses that were responsible for almost 95% of the world’s
incidence rate of cancer in 2008. Discuss ways in which these particular carcinogenic agents can be avoided or eliminated. Describe how you can avoid them as a health care worker. Identify how long after radiation exposure that cancer cause by the radiation may manifest itself.
- Papilloma virus - vaginal warts and cervical cancer
- avoid sexual contact - Hepatitis B and C - liver adenomas
- don’t share needles, prevent needle stick injuries, avoid skin exposure to blood, get the hep vaccine - Adeno-virus
- avoid people who are sick, cover mouth when coughing or sneezing, wash hands often - Epstein Barr Virus - B cell lymphoma
- “kissing virus” mainly spreads in saliva, don’t share drinks or other personal items with people who are infected - Herpes virus
- causes chicken pox/shingles, get vaccination for varicella and avoid sexual contact - HIV
- avoid sexual contact, don’t share needles, be careful with bodily fluids and blood - Human T cell leukemia lymphoma virus
- avoid transfusion, sharing needles, sexual intercourse, breast feeding when pregnant
Radiation will manifest itself:
For leukemia –> if you’re 15 years or younger, 6-7 year post
If you’re 45 years +, 20 year latent period
Multi organ solid cancers –> 30 year latent period
Delineate the source of ionizing radiation for most U.S. citizens, and discuss ways in which these particular sources of carcinogens can be minimized or avoided. Describe how you can
avoid them as a health care worker.
Sources: x rays, gamma rays, beta particles, alpha particles
Most common source of radiation in the U.S. = medical tests
ex) computed tomography, nuclear medicine, interventional fluoroscopy, conventional radiography fluoroscopy
How to avoid: use protective equipment! Stand behind wall or shield. Wear the lead vests they give you.
Describe the “Bystander Effect” as it relates to carcinogenesis as a result of radiation therapy.
Bystander effect – directly irradiated cells can lead to genetic defects in bystander cells (innocent cells) even though they themselves received no direct radiation. It’s all because of gap junctions (intracellular signaling). These defects get passed on to progeny cells.
Identify all of the types or areas of carcinogenesis that have been positively linked to the use of tobacco, either through smoking or chewing. Identify the percent of deaths in the United States that are directly attributable to effects of tobacco, how many chemicals have been identified in tobacco, and how many of those have been determined as toxic so far.
Areas of carcinogenesis:
- mouth, lip, nasal cavity, larynx
- lung
- pancreas
- esophagus
- liver
- colorectum
- acute leukemia
- stomach
- kidney
- cervical
- myeloid lymphoma
- ovarian
Percent of deaths in U.S. = 20%
60 carcinogens found in tobacco and over 4000 chemicals found in tobacco.
Identify the types or areas of cancer for which Ethanol has been implicated as the cause of. Describe the mechanism by which ethanol contributes to colon cancer, esophageal cancer
and liver cancer.
Ethanol is linked to breast cancer, colorectal cancers, oral, pharynx, esophagus, and liver cancer.
It contributes to colon, esophageal, and liver cancer by dissolving tar so the 60 carcinogens can be carried from the lungs to the rest of the body.
Describe the role exercise, vegetables, fruits, in carcinogenesis as well as red meats,
processed meats, and smoked meats, and preservatives have on cell transformation to cancer.
Exercise - reduces the risk of breast and colon cancers
Veggies -
Fruits -
Red Meats -
Processed Meats -
Preservatives - nitrites, saccharin with salts = dimethylnitrosamine
Describe the relationship of obesity to cancer and delineate the mechanisms by which obesity and type II diabetes contribute to carcinogenesis.
Obesity is linked to 15% of cancer deaths in men and 20% in women.
Types: colorectal CA, endometrium, pancreatic, kidney, breast cancer, esophageal
Caused by:
A. Greater Lipid Peroxidation
B. Insulin resistance leading to increased insulin and IGF-1. Both promote cell division and inhibit apoptosis.
C. Increase production of sex hormones.
Obestiy –> Insulin Resistance–> Type II DM
Insulin resistance –> Obesity
*positive feedback! Both obesity and DM II predipose you to CA
Describe the mechanism by which UV light (natural of tanning beds) cause the
transformation of epidermal cells to cancer cells. Name the three types of skin cancer.
UV light exposure causes the formation of ROS (reactive oxygen species.)
Causes oxidative stress to the cells.
First and second degree burn triggers inflammation. (macrophages release cytokines that promote cell proliferation, VEGF, PDGF, CHRONIC INFLAMMATION = continued proliferation!!!)
- inflammation also produces ROS which promote mutations and block DNA repair mechanisms.
Long term this can lead to carcinogenesis!
Types of skin cancers:
- Basal cell carcinoma
- Squamous cell carcinoma
* most susceptible ppl. are light complexion, light colored eyes, fair hair, burn rather than tan - Melanoma - due to blistering over doses at a young age. Constantly exposed areas have less risk. Occurs in less exposed areas. Trunk for men and legs for women.
List 7 ways that cancer cells can avoid the tumor surveillance system, especially the Tc and
NK cells.
- If a tumor expresses a tumor specific antigen, the immune system will reject the tumor!
B lymphoctyes (activated by TSA) –> activate complement, ADCC (Fc portion binds to monocytes, B cells, Neutrophils, killer cells)
NK cells - first line of defense, activated when cells down regulate MHC 1 marker
Tc cells- most effective for tumor rejection, attack TSA antigens ( on MHC 1 marker)
How do they escape?
- mask or modify their antigens by secreting immuno-suppresive substances ex) interleukin, prostaglandin E
- blocking factor, antibodies that bind to and block the antigen but don’t activate complement or bind to ADCC system
- Normal antigens activate suppressor lymphocytes
- Activate TAMS - phase 2 macrophages that promote healing
