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HemOnc Week 2 > ICL 7.2: Neoplasia II > Flashcards

ICL 7.2: Neoplasia II Flashcards

1
Q

which factors affect cancer incidence?

A
  • geographic factors
  • environmental/occupational exposures
  • age
  • genetics
  • presence of precursor lesions
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2
Q

what cancer is increasing at the most rapid rate worldwide?

A

malignant melanoma is increasing at the most rapid rate of all cancers

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3
Q

what cancer is most common China?

A

nasopharyngeal carcinoma associated with EBV

SCC of the esophagus associated with alcohol abuse and smoking

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4
Q

what cancer is most common in Japan?

A

gastric adenocarcinoma associated with smoked foods

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5
Q

what cancer is most common in Southeast Asia?

A

hepatocellular carcinoma associated with HBV and HCV

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6
Q

what cancer is most common in Sub-Saharan Africa?

A

Burkitt lymphoma associated with EBV

Kaposi sarcoma associated with human herpesvirus 8

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7
Q

what are some environmental factors that can cause cancer?

A
  • microbial pathogens (HPV, EBV)
  • smoking
  • alcohol consumption
  • diet
  • obesity
  • reproductive history
  • environmental carcinogens
  • UV, radiation, medications, hormones
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8
Q

what kind of cancers can smoking cause?

A

carcinomas of the lung, mouth, pharynx, larynx, esophagus, pancreas, bladder

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9
Q

what kind of cancers can alcohol consumption cause?

A

carcinomas of the oropharynx, larynx, esophagus and liver

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10
Q

what population has the highest risk of prostate cancer?

A

african americans > whites > Japanese

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11
Q

what population have increased risk of skin cancer?

A

more common in fair-skinned people than dark skinned

due to the protective effect of melanin against UV light

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12
Q

what populations have increased risk of breast cancer?

A

Japanese and Asian women have lower incidence of breast cancer compared to north america and european women

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13
Q

how is age related to cancer?

A

increase in age is associated with increased incidence

epithelial cancers are more common as you get older with less leukemias and lymphomas

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14
Q

what cancers is most common in people under 15?

A

leukemias & lymphomas

neuroblastomas

Wilm tumors

retinoblastoma

bone & skeletal muscle

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15
Q

what cancer are most common in 15-34 years old?

A

leukemia

breast

brain

cervix

colon

soft tissue

NHL

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16
Q

what cancers are most common in 35-54 years old?

A

lung

breast

colon

ovary

cervix

brain

pancreas

NDL

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17
Q

what cancers are most common in 55-74 years old?

A

lung

breast

colon

prostate

ovary

pancreas

NHL

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18
Q

what are autosomal dominant inherited cancer syndromes?

A

inheritance of a single mutant alley in the cancer suppressor gene

this single allele is enough to lead to cancer

there’s usually an associated marker phenotype

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19
Q

what are familial cancers?

A

familial clustering of specific forms of cancer but the transmission pattern is not clear

no marker phenotype

familial forms of common cancers are recorded: breast, ovary, colon, brain and

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20
Q

what are autosomal recessive syndromes of defective DNA repair?

A

can cause development of tumors if there’s two defective alleles in the cancer suppressor gene

ex. XP, Bloom syndrome, ataxia-telangiectasia

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21
Q

what are the three types of hereditary cancer?

A
  1. autosomal dominant inherited cancer syndromes
  2. familial
  3. autosomal recessive syndromes of defective DNA repair
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22
Q

what types of cancers are autosomal dominant inherited?

A
  • childhood reinoblastoma
  • familial adenomatous polyposis (FAP)
  • MEN syndromes
  • neurofibromatosis I & II
  • von Hippel-Lindau syndrome
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23
Q

what types of cancers are inherited familial cancers?

A

breast

ovary

colon

brain

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24
Q

what types of cancer are recessive syndromes of defective DNA repair?

A

XP

Bloom syndrome

ataxia-telangiectasia

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25
Q

what is dysplasia?

A

pre-cancer lesions

disruption of normal patterns of cellular maturation and organization in epithelial cells resulting in cytologic atypic of the dysplastic cells within the epithelium

risk of profession to cancer increases with increasing severity of the dysplasia

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26
Q

what’s the most common dysplasia?

A

cervical

CIN = cervical intraepithelial neoplasia

can be I, II, or III grade
I = low grade
II & III high grade

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27
Q

what is carcinoma in situ?

A

when dysplasia involves the entire thickness of the epithelium but remains confined to the basement membrane

it’s a pre-invasive neoplasm

there’s a high probability of progression to invasive carcinoma - 70% of cervical CIS progresses tp invasive cancer in 12 years if untreated

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28
Q

how do you cure CIS?

A

complete removal

29
Q

what cancer does cirrhosis of the liver usually lead to?

A

hepatocellular carcinoma

30
Q

what cancer does atrophic gastritis of pernicious anemia usually lead to?

A

stomach cancer

31
Q

what cancer does chronic ulcerative colitis usually lead to?

A

colonic adenocarcinoma

32
Q

what cancers does leukoplakia or oral and genital mucosa lead to?

A

squamous cell carcinoma

33
Q

what cancer does hyperplasias and metaplasia lead to?

A

hyperplasia = the enlargement of an organ or tissue caused by an increase in the reproduction rate of its cells

endometrial hyperplasia

bronchial mucosal metaplasia/dysplasia of smokers

Barrett’s metaplasia of esophagus

34
Q

what is barrett’s metaplasia?

A

metaplasia = abnormal change in the nature of a tissue

when there’s repeated damage of the esophagus the tissue changes into globule cells to protect itself and overtime it can lead to dysplasia

35
Q

what benign neoplasm DOES have a risk for developing to malignant neoplasms?

A

colon polyps! especially villous adenomas

with familial polyposis, 100% develop cancer by the age of 50!

you have to routinely remove them to reduce risk

risk of invasive carcinoma is related to size and histological type of the lesion

36
Q

what are the two steps of chemical carcinogenesis?

A
  1. initiation

2. promotion

37
Q

what is an initiator of chemical carcinogenesis?

A

something that can cause direct damage to the DNA, leading to mutations

all initiating agent have highly reactive electrophile groups that directly damage DNA

38
Q

what are direct acting carcinogen agents?

A

direct acting agents don’t require metabolic conversion!

ex. alkylating ages used for chemotherapy

39
Q

what are indirect-acting carcinogen agents?

A

require metabolic conversion to become ultimate carcinogens

most are metabolized by cytochrome P-450 mono-oxygenates which are polymorphic

the activity of indirect-acting agents varies a lot between individuals

40
Q

what are some examples of chemical carcinogens?

A
  • alkylating agents
  • polycyclic hydrocarbons
  • benzopyrine
  • azo dyes
  • naturally occurring carcinogens
  • nitrosamines and amides
41
Q

what is promotion?

A

second step of chemical carcinogenesis

promoters are not a mutagenic agent - it’s something that triggers cell division

when mutated cells divide, you pass on the genetic variation to the progeny

42
Q

what are examples of promoters of chemical carcinogenesis?

A

hormones

phorbol esthers

phenols

drugs

43
Q

what are some examples of alkylating agents?

A

they’re chemical carcinogens like:

cyclophosphamide

bulsulfan

they increase the risk for another neoplasm

44
Q

what are some examples of polycyclic hydrocarbons?

A

they’re chemical carcinogens like:

fossil fuels

also produced from animal fats during broiling or grilling meats, smoked meats and fish

45
Q

what are benzopyrines?

A

chemical carcinogens that are an active components of soot

they’re formed during high pressure combustion of tobacco

46
Q

what are azo dyes?

A

B-naphthylamine (alanine dye)

they’re chemical carcinogens!

47
Q

what are some naturally occurring carcinogens?

A

aflatoxin B1

it’s produced by aspergillum flavus

associated with HCC in africa = hepatocellular carcinoma

48
Q

what are nitrosamines and amides?

A

chemical carcinogens that can be synthesized in GI tract from ingested nitrites and contribute to gastric cancer

49
Q

what are some other chemical carcinogens?

A

asbestos

vinyl chloride

nickel

50
Q

when do tumors occur?

A

when there’s exposure to an initiator FOLLOWED BY a promoter

51
Q

what does UV radiation cause?

A

increased incidence of squamous cell carcinoma, basal cell carcinoma and melanoma of the skin

risk depends on type of UV rays, intensity and quantity of melanin in the skin

UVB is the most potent mutagen

52
Q

how do you fix UV ray damage?

A

nucleotide excision repair = NER

53
Q

what disease is associated with a problem with the NER pathway?

A

xeroderma pigmentosum

autosomal recessive

inability to repair UV induced DNA damage

2000x increased risk of skin cancers in sun-exposed skin

neurologic abnormalities

54
Q

what is ionizing radiation?

A

x-rays, gamma rays, alpha particles and B particles

also includes therapeutic radiation! there’s an increased risk for thyroid cancer in people getting head and neck radiation

also you should avoid CT scans in kids because it increases the risk for leukemia and brain tumors

55
Q

which organs have the highest and lowest sensitivity towards ionizing radiation?

A

high = myelopoietic tissue, thyroid

moderate = breast, lungs, salivary glands

low = skin, bone, GI tract

56
Q

what are some types of microbial carcinogenesis?

A
  1. DNA viruses
  2. RNA viruses
  3. Others: helicobacter pylori
57
Q

what are DNA viruses?

A

microbial carcinogenesis

transiting DNA viruses integrate into and form stable associates with theist cell genome

viral genes that are transcribed early are important for transformation and are expressed in transformed cells

58
Q

what are some types of DNA viruses that lead to microbial carcinogenesis?

A

HPV

EBV

HepB

59
Q

how can HPV cause microbial carcinogenesis?

A

E6 and E7 proteins of high risk HPV disable important tumor suppressor proteins that regulate the cell cycle like p53, p21 and RB

HPV 16 and 18 are present in 85% of invasive squamous cell cancers, cervial dysplasia and carcinoma in-situ (high risk)

HPV 6 and 11 are associated with genital warts (low risk)

60
Q

which cancers is HPV implicated in?

A

squamous cell carcinoma of the cervix and anogenital region

oral cancers

laryngeal cancers

61
Q

how does the EBV virus cause microbial carcinogenesis?

A

Epstein-Barr Virus is a member of the herpes family

EBV infects B-lymphocytes and possibly epithelial cells of the oropharynx

uses complement receptors CD21 to attach and infect B-cells

infection of B-cells is usually latent

62
Q

which cancers is EBV implicated in?

A

African form of Burkitt lymphoma

B-cell lymphomas in immunosuppressed patients

Hodgkin lymphoma

nasopharyngeal carcinomas

63
Q

how is EBV related to Burkitt lymphoma?

A

Burkitt lymphoma is a neoplasm of B-lymphocytes

it’s the most common childhood tumor in Central Africa and New Guinea

it’s association with EBV is strong: >90% of African tumors carry the EBV genome

all tumors have t(8,14) translation

64
Q

which cancer is HBV associated with?

A

70-85% of hepatocellular carcinomas worldwide are associated with HepB or HepC

HBV is more common Africa so they also have the highest incidence of HCC

65
Q

how does HBV cause HCC?

A

multifactorial

HBV and HCV genomes don’t encode any viral oncopmoteins

HBV DNA does integrate with human genome but there’s no consistent pattern

it’s thought that the mechanism that leads to DNA damage is immunologically mediated chronic inflammation with hepatocyte death leading to regeneration which over time leads to genomic damage

66
Q

which RNA virus is associated with cancer?

A

Human T-cell leukemia virus type 1 = HTLV-1

it’s the only retrovirus implicated in the cause of cancer!

endemic in Japan and Caribbean

has a tropism for CD4+ T cells

to get infected, there has to be transmission of infected T-cells via sexual intercourse, blood products or breast feeding

67
Q

what types of cancer is HTLV-1 associated with?

A

it’s an RNA virus where leukemia develops in 3-5% of infected individuals after a latent period of 4-60 years

68
Q

which bacteria can cause cancer?

A

helicobacter pylori

linked to gastric adenocarcinomas and gastric lymphomas

can treat with antibiotics

HemOnc Week 2 (14 decks)

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