03/02c Neoplasia II

Question 1

What is epidemiology?

Answer 1

The study of the distribution and determinant of health-related states or events in specified populations, the the application of this study to control of health problems

Question 2

What is the definition of cancer INCIDENCE?

Answer 2

Incidence is how many people are diagnosed with cancer in a given time period (often 1 year)

Question 3

What is the definition of cancer PREVALENCE? What factors determine prevalence?

Answer 3

Prevalence is how many people (total) have the cancer in a given time period
Depends on incidence, length of survival, and mortality rates

Question 4

What percentage of the US population has had cancer?

Answer 4

8.2%

Question 5

What is the relationship between cancer and age?

Answer 5

Cancer is largely a disease of the older population; incidence increases with age

Question 6

What are the top four most common cancers that cause death in the US?

Answer 6

Lung
Colon
Breast
Prostate

Question 7

Why have lung and bronchus cancer death rates increased so much between the 1930s and now?

Answer 7

Smoking!

Question 8

What is the absolute difference in cancer survival rates between the white and black populations?

Answer 8

10%

Question 9

What happens to your chances of getting a certain type of cancer if you move to different country?

Answer 9

You acquire the cancer rates of the country that you move to

Question 10

What are most cancers caused by? What does this mean?

Answer 10

“The environment”

The majority of cancer are thus preventable, if we can figure out what in the environment is causing them

Question 11

What are three characteristics of inherited cancers that distinguish them from sporadic cancers?

Answer 11

Cancer develops in a large proportion of afflicted patients
Usually early onset
Often site-restricted

Question 12

What percentage of all cancers are inherited cancers?

Answer 12

5-10%

Question 13

What are the three broad categories of inherited cancers?

Answer 13

Autosomal dominant
Autosomal recessive
Unclassified familial clusters

Question 14

What are unclassified familial clusters?

Answer 14

Family that has a high rate of cancer, but with an unclear mechanism of inheritance and no genetic defect identified

Question 15

What are four important features of autosomal dominant cancers?

Answer 15

Have very specific sites or tissues that are affected by cancer
Can have incomplete penetrance and variable expressivity
Can have multiple benign tumors in the target tissue, as well as malignant tumors
Can have characteristics non-neoplastic lesions in other tissues

Question 16

What are two classic examples of non-neoplastic lesions characteristic in cases of neurofibromatosis?

Answer 16

Café au lait spots on the skin

Lisch nodules in the eye

Question 17

How much more likely are you to develop retinoblastoma if you have the mutated Rb gene?

Answer 17

10,000x more likely

Question 18

What are five important features of autosomal recessive cancers?

Answer 18

Rare in comparison to autosomal dominant cancers
Usually have complete penetrance
Tumors usually arise in sites exposed to mutagens (UV light, radiation, etc.)
Typically have complex, multi-system effects
Mostly due to defects in DNA repair

Question 19

What three things can happen to a cell that has accumulated a large amount of DNA damage?

Answer 19

Enters senescence (irreversible dormancy)
Undergoes apoptosis
Develops unregulated cell division, leading to the formation of a tumor

Question 20

What is ataxia telangiectasis?

Answer 20

Autosomal recessive cancer
Characterized by progressive neurologic impairment, cerebellar ataxia, immundeficiency with susceptibility to infections, impaired organ maturation, and X-ray sensitivity
Mutation in a gene that senses DNA double-stranded breaks and initiates cell cycle arrest or cell death

Question 21

What is xeroderma pigmentosum?

Answer 21

Autosomal recessive cancer in which nucleotide excision repair enzymes are mutated, and thus cells cannot repair damage to DNA caused by UV light
Patients present with severe sunburns after only a short sun exposure, and are susceptible to developing basal cell carcinoma and other skin malignancies at a young age

Question 22

What is Lynch Syndrome?

Answer 22

Hereditary Nonpolyposis Colon Cancer (HNPCC) - most common inherited colon cancer
Causes cancers of the colon, endometrium, and ovary
Autosomal dominant inheritance pattern
Caused by a DNA repair defect

Question 23

What three features of a cancer would lead you to believe it was an unclassified familial cancer?

Answer 23

1) Cancers seen in multiple close relatives
2) Multiple cancers seen in individuals
3) Persistence of cancers over several generations

Question 24

What broad non-hereditary medical condition can predispose you to cancer?

Answer 24

Chronic inflammation

May be due to infection, autoimmunity, or be medically induced

Question 25

What are some cancers that are caused by inflammation associated with infection?

Answer 25

Helicobacter pylori gastritis - gastric cancers Chronic osteomyelitis - squamous cell cancer in fistula tracts Viral hepatitis - liver cancer

Question 26

What are some cancers that are due to inflammation caused by autoimmune conditions?

Answer 26

Colon cancer - ulcerative colitis | Bile duct cancer - sclerosing cholangitis

Question 27

What is a pre-cancerous lesion?

Answer 27

A lesion with a marked increase in cancer at the site | Obligate precursor - remove it and cancer is prevented, but not all will progress to cancer

Question 28

What is a carcinogen?

Answer 28

An external agent that increases the incidence of malignant neoplasms, reduces their latency, or increase their severity or multiplicity

Question 29

What important information can be provided by studying occupational cancers?

Answer 29

Identification of specific carcinogens present in various occupations

Question 30

What are the six classes of carcinogens?

Answer 30

1) Chemical/occupational 2) Radiations (including UV light) 3) Infectious 4) Dietary exposures 5) Therapeutic/iatrogenic 6) Social habits

Question 31

What are chemical carcinogens?

Answer 31

Often highly reactive electrophiles - react with nucleophilic sites in the cell like DNA, RNA, and proteins Can be direct (chemical is the active carcinogen) or indirect (procarcinogen - metabolite of the chemical is the active carcinogen)

Question 32

What are four examples of procarcinogens?

Answer 32

Polycyclic aromatic hydrocarbons (in cigarette smoke) Aromatic amines Naturally occurring carcinogens (peanut mold) Nitrosamines and amides (nitrate preservatives)

Question 33

What enzymes are responsible for metabolizing and activating most known carcinogens?

Answer 33

Cytochrome P450-dependent mono-oxygenases

Question 34

What is one enzyme that can inactivate procarcinogens? What chemical does it act on?

Answer 34

Glutathione-S-transferase (GST) - inactivates polycyclic aromatic hydrocarbons

Question 35

What cancer is caused by UV light?

Answer 35

Skin cancer!

Question 36

What cancers are caused by ionizing radiation (X-rays, gamma rays)?

Answer 36

Leukemia, thyroid, and many others

Question 37

What viruses are capable of causing cancer? Name four

Answer 37

HPV - cervical cancer EBV - lymphoma Hepatitis B and C - liver cancer Human T-cell lymphotrophic virus-1 - leukemia/lymphoma

Question 38

What parasites are capable of causing cancer? Name two

Answer 38

Shistosoma haematobium - bladder cancer | Opisthorchis viverrini - bile duct cancer

Question 39

Name two dietary carcinogens

Answer 39

Aflatoxins (peanut mold) - liver cancer | Arsenic - lung and skin cancer

Question 40

What are two examples of therapeutic agents that can cause cancer?

Answer 40

Many chemotherapeutic agents - lymphomas and leukemias | Estrogenic hormones - endometrium and breast cancer

Question 41

What are six examples of cultural and lifestyle habits that can cause cancer?

Answer 41

1) Tobacco smoke - lung, respiratory tract, kidney, bladder, and pancreas cancers 2) Ethanol - liver and GI cancers 3) Betal quid - mouth cancer 4) Smokeless tobacco - mouth cancer 5) Chinese salted fish - nasopharyngeal cancer 6) Obesity - colon, endometrial, and breast cancers

Question 42

What are the leading modifiable risk factors for cancer worldwide? Name four

Answer 42

1) Tobacco smoking and ethanol consumption 2) Diet low in fruits and vegetables 3) Obesity (in developed countries) 4) Unprotected sexual habits (cervical cancer)

Question 43

Carcinogenesis requires two big things - what are they?

Answer 43

An INITIATOR and a PROMOTER

Question 44

What are initiators and promoters? How do they cause cancer?

Answer 44

Initiators are usually agents that cause DNA damage or mutations Promoters usually cause cellular proliferation and expand the number of cells with damage This leads to a multi-step model of carcinogenesis Neoplasia only occurs when initiators are administered prior to promoters

Question 45

How do the statistics of childhood cancers differ from those of adults?

Answer 45

Rare overall (only 1% of new cancers) Second leading cause of death before age 15 Better survival rates - 80% survive 5 years or more Types of cancers seen are very different - adult type carcinomas are rare

Question 46

What types of cancers are most commonly seen in children?

Answer 46

Leukemias Primitive brain tumors "Small round blue cell" tumors of solid organs