B2.078 Cancer Biology

Question 1

how does chromic inflammation affect cancer risk?

Answer 1

increases risk due to increasing cell proliferation and increased possibility for damage (ROS)

Question 2

what are proliferative precursor lesions?

Answer 2

metaplasia- sustained injury

hyperplasia- hormonal stimulation

Question 3

how does immunodeficiency affect cancer risk?

Answer 3

increases risk due to inability to fight off cancer cells without immuno-surveillance mechanisms

Question 4

what type of inheritance is exhibited in familial cancer?

Answer 4

polygenic or multifactorial

can’t pinpoint specific genes but appears to run in families

Question 5

what are some clinical features of hereditary cancer?

Answer 5

multiple affected relatives
early age of cancer onset
bilaterally affected organs
multiple primary cancers in same individual
autosomal dominant pattern

Question 6

what are the differences in risk associated with hereditary cancer associated w tumor suppressor genes vs, DNA repair genes?

Answer 6

both risks elevated
tumor suppressor mutation = virtually 100% likelihood of getting cancer
DNA repair mutation = highly likely, but may develop later or possibly not at all if DNA damage never occurs in a cancer specific gene

Question 7

how many retinoblastoma patients have unilateral vs bilateral tumors?

Answer 7

70% uni

30 % bi

Question 8

what percentage of retinoblastomas are hereditary?

Answer 8

40%

all bilateral are hereditary, but not all hereditary forms result in bilateral tumors

Question 9

how does heritable retinoblastoma affect risk of developing other cancers?

Answer 9

400 fold increase

Question 10

what tumor suppressor gene is associated with Li-Fraumeni Syndrome?

Answer 10

TP53

Question 11

what are some tumors that often result from Li-Fraumeni Syndrome?

Answer 11

breast carcinoma
soft tissue sarcoma
brain tumors
osteosarcoma
leukemia

Question 12

what gene is associated with familial adenomatous polyposis (FAP)?

Answer 12

APC

Question 13

how is FAP recognizable?

Answer 13

100s-1000s of colonic polyps in teenage years

Question 14

what is the best treatment for FAP?

Answer 14

removal of the colon early in life

Question 15

what is HNPCC?

Answer 15

hereditary non-polyposis colorectal cancer

Lynch Syndrome

Question 16

differentiate between HNPCC and FAP

Answer 16

HNPCC: early onset, but later than FAP
germline mutation in mismatch repair genes
5% of colon cancer
recognized by DNA slips in microsatellites alerting to poor repair mechanisms (MSH)
FAP: very early onset
germline mutation in APC gene
1% of all colon cancer
recognized by polyps

Question 17

what percentage of breast cancers are inherited?

Answer 17

5-10%

Question 18

how does inheriting a BRCA gene mutation affect lifetime risk of cancer?

Answer 18

40-85% increase in breast cancer risk

BRCA1 55% and BRCA2 25% ovarian cancer risk

Question 19

what are the steps of chemical carcinogenesis?

Answer 19

initiation (permanent DNA damage)

promotion (proliferation stimulation)

Question 20

what are direct acting carcinogens?

Answer 20

alkylating/acylating agents
usually weak
used in chemotherapy

Question 21

what are indirect acting carcinogens?

Answer 21

aromatic hydrocarbons, dyes, toxins
metabolic conversion required (cp450)
strong carcinogens

Question 22

what are the 2 types of radiation carcinogenesis?

Answer 22

UVB exposure and ionizing radiation

Question 23

what is the mechanism by which UVB exposure causes cancer?

Answer 23

formation of pyrimidine dimers

normally repaired by nucleotide excision repair (XP pathway), but can be overwhelmed or dysfunctional

Question 24

what is the mechanism by which ionizing radiation causes cancer?

Answer 24

chromosomal breakage, translocations, point mutations

Question 25

what are some examples of microbial carcinogens?

Answer 25

retrovirus- HTLV-1 DNA virus- HPV, EBV, HBV, HHV8 bacteria- helicobacter pylori

Question 26

how do microbial carcinogens cause cancer?

Answer 26

viral integration into genome direct activation/proliferation by interaction w tumor suppressor genes increased genomic instability immunological damage with resultant proliferation of lymphocytes/epithelial cells

Question 27

how do HPV E6 and E7 inactivate Rb protein?

Answer 27

``` inhibits RB-E2F complex increases CDK4/cyclin D1 inhibits p21 inhibits p53 increases telomerase ```

Question 28

what disease is associated with EBV?

Answer 28

Burkett lymphoma set up uncontrolled B-cell proliferation resulting in mutations (increased C-MYC expression)

Question 29

which oncogenes are affected by translocations?

Answer 29

``` c-MYC (burkitt lymphoma) -t(8:14) BCL2 (follicular lymphoma) BCR/ABL (chromic myeloid leukemia) -t(9:22) ```

Question 30

which tumor suppressor gene is affected by deletions?

Answer 30

Rb

Question 31

which oncogenes are affected by gene amplification?

Answer 31

N-MYC (neuroblastoma) | HER-2/neu (breast cancer)

Question 32

which oncogenes are affected by point mutations?

Answer 32

RAS (many cancers)

Question 33

what are some epigenetic changes that can affect dysregulation of cancer genes?

Answer 33

local hypermethylation, global changes in methylation, changes in histones

Question 34

what is a growth fraction?

Answer 34

proportion of cells in a cell cycle that are actively dividing

Question 35

what are the 3 routes of cancer spreading?

Answer 35

hematogenous lymphatic body cavity seeding

Question 36

what are some local effects of cancer related to direct tumor growth?

Answer 36

``` mass bleeding compression/obstruction rupture/torsion vascular compromise necrosis functional manifestations ```

Question 37

what are the two major systemic effects of cancers?

Answer 37

cachexia - profound weakness, anorexia, anemia paraneoplastic syndrome- clinical findings not directly explained by anatomic location or functional output of the cancer

Question 38

what are some features of cachexia?

Answer 38

equal loss of fat and lean muscle elevated basal metabolic rate evidence of systemic inflammation

Question 39

what are characteristics of a good screening test?

Answer 39

``` high sensitivity variable specificity high NPV variable PPV variables dependent on prevalence ```

Question 40

what are some types of cancer screening tests?

Answer 40

``` clinical exam and procedures radiological imaging biochemical measurement cytologic exam histologic exam nucleic acid testing for markers ```