Flashcards in Path: Epidemiology of Cancer Deck (38):
The incidence of cancer varies with all of the following except:
age, sex, race, comorbidities, geography, genetic background,
Why is geographic variation in cancer incidence a risk factor?
thought to stem from different environmental exposures
Cancers are most common in adults over age ___.
Important environmental factors implicated in carcinogenesis include ...?
infectious agents, smoking, alcohol, diet, obesity, reproductive history, and carcinogens
There are 2 conditions related to tissue injury and the immune system that increase the risk of cancer. What are they?
chronic inflammation; immunodeficiency
____ cancer is much more fatal than prostate or breast cancer.
Why are most brain tumors in children benign yet fatal?
Most of the brain tumors in children are technically “benign”, but they tend to be fatal because they cannot be surgically removed, often do not respond to non-surgical therapies, and their autonomous growth in the unexpandable space of the skull compresses vital brain structures.
About 60% of childhood cancer deaths are due to ____ ____ and ____ ____.
acute leukemias; brain tumors
Acquired conditions that predispose to cancer can be divided into 3 categories. Please name them.
1. chronic inflammations
2. precursor lesions
3. immunodeficiency states
Chronic inflammatory disorders and precursor lesions include many conditions that are all associated with ____ ____ ____. What is the significance of this?
increased cellular replication; this state creates a "fertile" soil for development of malignant tumors because of the repeated rounds of cell replication
Immunodeficiency states predispose to what kind of cancers?
Precursor lesions can be defined as ...?
localized morphologic changes that are associated with a high risk of cancer
The majority of tumor arising in the context of chronic inflammation are what kind of tumor?
Virtually all precursor lesions arise in what tissue and are associated with increased risk of what type of cancer?
epithelial tissue; carcinoma
How/why are pap smears useful?
they can detect dysplasia (precursor lesion) of the cervical endometrium before it becomes cancer
What is dysplasia?
disordered growth; cellular atypia and messed up architecture; not [yet] cancer
Normal uterine epithelium will have what histological features?
single basal cell layer; the higher cells and their nuclei are flatter than the basal cells; abundant glycogen in cytoplasm (appearing as clear cytoplasm)
When basaloid cells are located here in the cervix, the worse the dysplasia. Where is "here"?
"here" is higher in the epithelium
True or false: severe dysplasia looks pretty much the same as earl neoplasia, therefore can also be classified as carcinoma in situ.
False - severe dysplasia looks
pretty much the same as early neoplasia (carcinoma in situ), but is NOT cancer (yet)
What is CIN?
cervical intraepithelial neoplasia; the term for all dysplasia and carcinoma in situ seen in cerival epithelium
What is SIL?
squamous intraepithelial lesion, refers to cerival epithelium
Which leads to cancer: chronic inflammatory diseases infectious or non-infectious etiologies?
trick question - either etiology can lead to cancer
How does chronic inflammation lead to cancer? (3 areas of increased risk)
- increased cell proliferation to repair the tissue damage
- increase in the number of tissue stem cells - susceptible to mutation/transformation
- activated immune cells produce ROS that are directly genotoxic
What are 4 important examples of chronic inflammatory conditions that lead to cancer?
1. inflammatory bowel disease, esp. ulcerative colitis --> carcinoma of colon
2. chronic hepatitis, especially chronic hepatitis C --> hepatocellular carcinoma
3. chronic pancreatitis --> pancreatic carcinoma
4. chronic cholecystitis --> gallbladder carcinoma
Chronic epithelial injury often leads to metaplasia, which is what?
the replacement of one cell type with a second that is better able to survive the ongoing insult
What is helicobacter pylori gastritis and how does it lead to cancer?
infectious Gram-negative bacterium that injects its CagA, activates cell proliferation pathways, causes degradation of p53; epithelial cells are irritated by this and undergo metaplasia, a precursor to gastric adenocarcinoma
True or false: precursor lesions inevitably progress to cancer.
False - but they are associated with increased cancer risk
What are 3 examples of precursor lesions in the setting of chronic inflammation,a nd can be recognized by the presence of metaplasia?
1. Barrett esophagus - due to GERD
2. Squamous metaplasia of bronchial mucosa - due to smoking
3. Intestinal metaplasia of the stomach - due to chronic gastritis
What is non-inflammatory hyperplasia?
hyperplasia caused by something other than chronic inflammation; ex: endometrial hyperplasia is caused by sustained strogenic stimulation of the endometrium
Non-inflammatory hyperplasia can potentially progress to what type of cancer?
Another group of precursor lesions is ____ ____ that are at risk for malignant transformation.
benign neoplasms - but be aware that MOST benign neoplasms won't undergo malignant transformation
Benign tumors are at high risk for malignant transformation because they possess ____ ____.
What is leukoplakia?
a patch of white thickening of squamous epithelium that may occur in the oral cavity, penis, or vulva and gives rise to squamous carcinoma
____ is a lesion related to leukoplakia, but often already carcinoma in situ so it is beyond precursor.
Patients with immunodeficiency have a higher incidence of malignancies of certain types; what are they? (3)
1. B-cell lymphoma of B cells infected with EBV
2. Kaposi sarcoma, a proliferation of endothelial cells due to HHV8
3. Squamous cell carcinomas of cells infected with oncogenic HPV
What is the difference between lymphomas and leukemias?
lymphomas are solid hematologic malignancies and leukemias are liquid hematologic malignancies.
NF is an autosomal dominant disorder caused by mutations in the TSG ____, which has what function? What is the cellular phenotype of the NF mutation?
neurofibromin - a negative regulator of Ras; mutation in NF leads to Ras hyperactivity (hence tumor development)