Things that cause cancer Flashcards
1
Q
A mutation in the proto-oncogeneERBB1(EGFR)creates what?
A
Adenocarcinoma of the lung- mutation activation
2
Q
A mutation in the proto-oncogeneERRB2(HER) creates what?
A
Breast carcinoma- amplification mode of activation
3
Q
A mutation in the proto-oncogeneRETcreates what?
A
multiple endocrine neoplasia 2A and BFamilial medullary thyroid carcinomas
4
Q
A mutation in the proto-oncogenePDGFRBcreates what?
A
Gliomas & leukemiasOverexpression and translocation mode of activation
5
Q
A mutation in the proto-oncogene KITcreates what?
A
Gastrointestinal stromal tumors- seminomas, certain leukemiasPoint mutation mode of activation
6
Q
A mutation in the proto-oncogene ALKcreates what?
A
Adenocarcinoma of the lung- certain lymphomas, neuroblastomaTranslocation, fusion gene mode of activation
7
Q
A mutation in the proto-oncogene KRAScreates what?
A
Colon, lung and pancreatic tumors- activated via a point mutation
8
Q
A mutation in the proto-oncogene NRAScreates what?
A
Melanomas, hematologic malignancies
9
Q
A mutation in the proto-oncogene GNAScreates what?
A
pituitary adenoma, other endocrine tumors- activation via a point mutation
10
Q
A mutation in the proto-oncogene BRAFcreates what?
A
Melanomas- also leukemias, colon carcinoma, etc.BRAFis a RAS signal transduction
11
Q
A mutation in the proto-oncogene ABLcreates what?
A
Chronic myeloid leukemia, acute lymphoblastic leukemia- activated via a translocation, or a point mutation
12
Q
A mutation in the proto-oncogene C-MYCcreates what?
A
Burkitt Lymphoma- via translocation activation
13
Q
A mutation in the proto-oncogene N-MYCcreates what?
A
Neuroblastoma- small cell carcinoma of the lung- activated via an amplification
14
Q
A mutation in the proto-oncogene L-MYCcreates what?
A
Small-cell carcinoma of the lung- activated via amplification
15
Q
A mutation in the proto-oncogene CCND1 (Cyclin D)creates what?
A
Mantle cell lymphoma- also multiple myeloma- activation via a translocation mechanismBreast and esophageal cancers too- activation via an amplification mechanism
16
Q
A mutation inPAX8gene can make it act like a proto-oncogene and cause what?
A
Renal carcinoma
17
Q
A mutation inPAX5gene can make it act like a proto-oncogene and cause what?
A
Non-Hodgkin LymphomaLymphocytic leukemia
18
Q
A mutation in PAX3andPAX7genes can make it act like a proto-oncogene and cause what?
A
Embryonic rhabdomyosarcoma
19
Q
Chronic myelogenous leukemia is caused by translocation activation of what genes?
A
ABL 9q34/BCR 22q11
20
Q
Acute myeloid leukemia is caused by which translocation activation of what genes?
A
AML1 8q22/ETO 21q22PML 15q22/RARA 17q12
21
Q
Burkitt Lymphoma is caused by translocation activation of what genes?
A
c-MYC 8q24IGH 14q32
22
Q
Mantle cell lymphoma is caused by translocation activation of what genes?
A
CCND1 11q13IGH 14q32
23
Q
Follicular lymphoma is caused by translocation activation of what genes?
A
IGH 14q32BCL2 18q21
24
Q
Ewing sarcoma is caused by translocation activation of what genes?
A
FLI1 11q24EWSR1 22q12
25
Prostatic adenocarcinoma is caused by translocation activation of what genes?
TMPRSS2 (21q22.3)ETV1 (7p21.2)ETV4 (17q21)
26
What is the function of cyclines?
CDK4; D cyclins Form a complex that phosphorylates RB, allowing the cell to progress through the G1 restriction point
27
What is the function of the ARF family of genes?
INK4/ARF family (CDKN2A-C) p16/INK4a binds to cyclin D-CDK4 and promotes the inhibitory effects of RBp14/ARF increases p53 levels by inhibiting MDM2 activity
28
What is the function of RB?
Cell Cycle checkpoint component Tumor suppressive “pocket” protein that binds E2F transcription factors in its hypophosphorylated state, preventing G1/S transition; also interacts with several transcription factors that regulate differentiation
29
What is the function of p53?
Cell Cycle Checkpoint component Tumor suppressor altered in the majority of cancers; causes cell cycle arrest and apoptosis. Acts mainly through p21 to cause cell cycle arrest. Causes apoptosis by inducing the transcription of pro-apoptotic genes such as BAX. Levels of p53 are negatively regulated by MDM2 through a feedback loop. p53 is required for the G1/S checkpoint and is a main component of the G2/M checkpoint.
30
What is the NF1 gene?
Tumor suppressor geneProtein: Neurofibromin-1Function: Inhibitor of RAS/MAPK signalingFamilial Syndrome: Neurofibromatosis type 1 (neurofibromas and malignant peripheral nerve sheath tumors) - i.e. skin lesionsSpecific Cancers: Neuroblastoma, juvenile myeloid leukemia
31
What is the NF2 gene?
Tumor Suppressor GeneProtein: Neurofibromin-2/merlinFunction: Cytoskeletal stability, Hippo pathway signalingFamilial Syndromes: Neurofibromatosis type 2 (acoustic schwannoma and meningioma)Sporadic Cancers: Schwannoma, meningioma (leads to hearing loss and brain tumors, not skin lesions)
32
What is the PTEN gene significant for?
Tumor Suppressor GeneProtein: Phosphatase and tensin homologueFunction: Inhibitor of PI3K/AKT signalingFamilial Syndromes: Cowden syndrome (variety of benign skin, GI, and CNS growths; breast, endometrial, and thyroid carcinoma)Sporadic Cancers: Diverse cancers, particularly carcinomas and lymphoid tumors
33
What is the RB gene significant for?
Tumor Suppressor Gene Protein: Retinoblastoma (RB) proteinFunction: Inhibitor of G1/S transition during cell cycle progressionFamilial Syndromes: Familial retinoblastoma syndrome (retinoblastoma, osteosarcoma, other sarcomas)Sporadic Cancers: Retinoblastoma; osteosarcoma carcinomas of breast, colon, lung
34
What is the gene VHL significant for?
Tumor Suppressor Gene Protein: Von Hippel Lindau (VHL) proteinFunction: Inhibitor of hypoxia-induced transcription factors (e.g., HIF1α)Familial Syndromes: Von Hippel Lindau syndrome (cerebellar hemangioblastoma, retinal angioma, renal cell carcinoma)Sporadic Cancers: Renal cell carcinoma
35
What is the gene TP53 significant for?
Tumor Suppressor Gene Protein: p53 proteinFunction: Cell cycle arrest and apoptosis in response to DNA damageFamilial Syndromes: Li-Fraumeni syndrome (diverse cancers)Sporadic Cancers: Most human cancers
36
What are the genes BRCA1, BRCA2 significant for?
Tumor Suppressor Genes protein: Breast cancer-1 and breast cancer-2 (BRCA1 and BRCA2function: Repair of double-stranded breaks in DNAfamilial syndromes: Familial breast and ovarian carcinoma; carcinomas of male breast; chronic lymphocytic leukemia (BRCA2)sporadic cancers: rare
37
What is the gene WT1 significant for?
Tumor Suppressor Gene Protein: Wilms tumor-1 (WT1)Function: Transcription factorFamilial Syndromes: Familial Wilms tumorSporadic Cancers: Wilms tumor, certain leukemias
38
What is the gene MEN1 significant for?
Tumor Suppressor Gene Protein: MeninFunction: Transcription factorFamilial Syndromes: Multiple endocrine neoplasia-1 (MEN1; pituitary, parathyroid, and pancreatic endocrine tumors) Sporadic Cancers: Pituitary, parathyroid, and pancreatic endocrine tumors
39
What is the major form of underlying cancer and causal mechanism for Cushing Syndrome as a paraneoplastic syndrome?
Small-cell carcinoma of lungPancreatic carcinomaNeural tumors Mechanism: ACTH or ACTH-like substance
40
What is the major form of underlying cancer and causal mechanism for SIADH as a paraneoplastic syndrome?
Small-cell carcinoma of lung; Intracranial neoplasms Mechanism: Antidiuretic hormone or atrial natriuretic hormones
41
What is the major form of underlying cancer and causal mechanism for hypercalcemia as a paraneoplastic syndrome?
Squamous cell carcinoma of lungBreast carcinomaRenal carcinomaAdult T-cell leukemia/lymphoma Mechanism: Parathyroid hormone-related protein (PTHRP), TGF-α, TNF, IL-1
42
What is the major form of underlying cancer and causal mechanism for hypoglycemia as a paraneoplastic syndrome?
Ovarian carcinomaFibrosarcomaOther mesenchymal sarcomas Mechanism: Insulin or insulin-like substance
43
What is the major form of underlying cancer and causal mechanism for polycythemia as a paraneoplastic syndrome?
Gastric carcinomaRenal carcinomaCerebellar hemangiomaHepatocellular carcinoma Mechanism: Erythropoietin
44
What is the major form of underlying cancer and causal mechanism for carcinoid syndrome as a paraneoplastic syndrome?
Hepatocellular carcinomaBronchial adenoma (carcinoid)Pancreatic carcinomaMechanism: Serotonin, bradykinin
45
What is the major form of underlying cancer and causal mechanism for myasthenia gravis as a paraneoplastic syndrome?
Bronchogenic carcinomaThymic neoplasms Mechanism: Immunological
46
What is the major form of underlying cancer and causal mechanism for acanthosis nigricans as a paraneoplastic syndrome?
Gastric carcinomaLung carcinomaUterine carcinoma Mechanism: Immunological; secretion of epidermal growth factor
47
What is the major form of underlying cancer and causal mechanism for dermatomyositis as a paraneoplastic syndrome?
BronchogenicBreast carcinoma Mechansim: Immunological - look for heliotropic rash, mm weakness
48
What is the major form of underlying cancer and causal mechanism for Trousseau syndrome as a paraneoplastic syndrome?
Venous thrombosis (Trousseau phenomenon) Pancreatic carcinomaBronchogenic carcinomaOther cancers Mechanism: Tumor products (mucins that activate clotting)
49
What is the major form of underlying cancer and causal mechanism for DIC as a paraneoplastic syndrome?
Acute promyelocytic leukemiaProstatic carcinoma Mechanism: Tumor products that activate clotting
50
What is the major form of underlying cancer and causal mechanism for nonbacterial thrombotic endocarditis as a paraneoplastic syndrome?
Advanced cancers Mechanism: Hypercoagulability
51
What are some direct-acting carcinogens?
Alkylating Agents β-Propiolactone Dimethyl sulfate Diepoxybutane Anticancer drugs (cyclophosphamide, chlorambucil, nitrosoureas, and others) (Many cancers especially leukemias) Acylating Agents1-Acetyl-imidazole Dimethylcarbamyl chloride
52
What are some polycyclic and heterocyclic aromatic hydrocarbon procarcinogens that require metabolic activation?
Polycyclic and Heterocyclic Aromatic Hydrocarbons Benz[a]anthracene Benzo[a]pyrene Dibenz[a,h]anthracene 3-Methylcholanthrene 7,12-Dimethylbenz[a]anthracene
53
What are some aromatic amines, amides, and azo -dyes that are procarcinogenic?
Aromatic Amines, Amides, Azo Dyes 2-Naphthylamine (β-naphthylamine) Benzidine 2-Acetylaminofluorene Dimethylaminoazobenzene (butter yellow)
54
What are some procarcinogenic plant and microbial products?
Natural Plant and Microbial Products Aflatoxin B1 (Liver cancer via p53 inactivation) Griseofulvin Cycasin Safrole Betel nuts (Oral cancer)Others Nitrosamine and amides Vinyl chloride, nickel, chromium Insecticides, fungicides Polychlorinated biphenyls
55
Arsenic typically causes what kinds of occupation cancers? How is exposure mediated?
Lung carcinoma, skin carcinoma By-product of metal smelting; component of alloys, electrical and semiconductor devices, medications and herbicides, fungicides, and animal dips
56
Asbestos typically causes what kinds of occupation cancers? How is exposure mediated?
Lung, esophageal, gastric, and colon carcinoma; mesothelioma Formerly used for many applications because of fire, heat, and friction resistance; still found in existing construction as well as fire-resistant textiles, friction materials (i.e., brake linings), underlayment and roofing papers, and floor tiles
57
Benzene typically causes what kinds of occupation cancers? How is exposure mediated?
Acute myeloid leukemia Principal component of light oil; despite known risk, many applications exist in printing and lithography, paint, rubber, dry cleaning, adhesives and coatings, and detergents; formerly widely used as solvent and fumigant
58
Beryllium and beryllium compounds typically cause what kinds of occupation cancers? How is exposure mediated?
Lung carcinoma Missile fuel and space vehicles; hardener for lightweight metal alloys, particularly in aerospace applications and nuclear reactors
59
Cadmium and cadmium compounds typically cause what kinds of occupational cancers? How is exposure mediated?
Prostate carcinoma Uses include yellow pigments and phosphors; found in solders; used in batteries and as alloy and in metal platings and coatings
60
Chromium compounds typically causes what kinds of occupational cancers? How is exposure mediated?
Lung carcinoma Component of metal alloys, paints, pigments, and preservatives
61
Nickel compounds typically cause what kinds of occupational cancers? How is exposure mediated?
Lung and oropharyngeal carcinoma Nickel plating; component of ferrous alloys, ceramics, and batteries; by-product of stainless-steel arc welding
62
Radon and its decay products typically cause what kinds of occupational cancers? How is exposure mediated?
Lung carcinoma From decay of minerals containing uranium; potentially serious hazard in quarries and underground mines
63
Vinyl chloride typically cause what kinds of occupational cancers? How is exposure mediated?
Hepatic angiosarcoma Refrigerant; monomer for vinyl polymers (PVC industry); adhesive for plastics; formerly inert aerosol propellant in pressurized containers
64
Ultraviolet radiation causes what kinds of skin cancers?
•Nonmelanoma skin cancers - total cumulative exposure to UVB/UBC radiation•squamous cell carcinoma, basal cell carcinoma•Melanomas - intense intermittent exposure (sunbathing)
65
Ionizing radiation - electromagnetic or particulate - can cause what kinds of tumors via what mechanisms?
•Medical or occupational exposure, nuclear plant accidents (decreasing order)•Acute and chronic myeloid leukemia•Cancer of the thyroid in the young•Cancers of the breast, lungs, and salivary glands•Radioactive mine workers have 10X increase in lung cancer•Cancers of skin, bone, and GI tract (x-ray researchers - skin cancers)•Atomic bomb detonations•Leukemias-principally acute and chronic myelogenous after 7 years•Solid tumors afterwards (e.g., breast, colon, thyroid, and lung) Intrinsic Field Subtractor - inability to wear clothing, blue skin coloration, exiling yourself to Mars, not killing Veidt and foiling his dastardly plan
66
What RNA viruses are oncogenic? What cancers can they cause?
•HTLV-1 – adult T-cell leukemia/lymphoma•HCV – hepatocellular carcinoma
67
What DNA viruses are oncogenic? What cancers can they cause?
•HBV – hepatocellular carcinoma•HPV- papillomas (types 1, 2, 4, 6, 7, & 11), carcinomas of cervix, anus, penis & oropharynx (types 16 &18)•HHV-8 – Kaposi sarcoma & primary effusion lymphoma•EBV – Burkitt lymphoma, Hodgkin lymphoma & nasopharyngeal carcinoma•CMV (HHV-5) – mucoepidermoid carcinoma•Merkel cell polyomavirus – Merkel cell carcinoma
68
What fungi and parasite infections can cause cancer?
•Fungi•Aspergillus – aflotoxin B1-associated hepatocellular carcinoma (p53 mutation)•Parasites•Schistosoma haematobium – bladder cancer•Schistosoma japonicum – colon cancer•Opisthorchis viverrini – cholangiocarcinoma
69
What bacterial infections can cause cancer?
•Helicobacter pylori – extranodal marginal zone (MALT) lymphoma and gastric adenocarcinoma
70
What are 5 inherited autosomal recessive syndromes of defective DNA repair?
Xeroderma pigmentosum (nucleotide excision repair of cross-linked pyrimidine dimers)Hereditary nonpolyposis colon cancer syndrome (DNA mismatch repair)Ataxia-telangiectasia (DNA repair by homologous recombination)Bloom syndrome (DNA repair by homologous recombination)Fanconi anemia (DNA repair by homologous recombination)
71
What are some examples where there are familial clustering of cancer cases, but the role of the inherited predisposition is unclear on an individual level?
Breast cancer (BRCA1 & BRCA2)Ovarian cancer (BRCA1 & BRCA2)Pancreatic cancer (BRCA2)
72
What are some inherited autosomal recessive conditions with defects in DNA repair?
Xeroderma pigmentosaAtaxia telangiectasiaBloom SyndromeFanconi anemia
73
What is abnormal in xeroderma pigmentosa, and what does it result in?
Autosomal recessive•Xeroderma pigmentosa - Nucleotide excision repair abnormality associated with extreme sensitivity to ultraviolet (UV) rays affects the eyes and skin (cancers), may also have CNS problems (increased pyrimidine dimers)
74
What is abnormal in ataxia telangiectasia, and what does it result in?
Autosomal recessive•Ataxia telangiectasia – ATM gene defect (involved in DNA repair) associated with progressive difficulty with coordinating movements, weakened immune system, leukemias and lymphomas
75
What is abnormal in Bloom syndrome, and what does it result in?
Autosomal recessive•Bloom syndrome – Helicase abnormality associated with short stature, sun-sensitive skin changes, an increased risk of cancer, and other health problems
76
What is abnormal in Fanconi anemia? What does it result in?
Autosomal recessive•Fanconi anemia – FA process defects associated with aplastic anemia, hypopigmentation, café-au-lait spots, skeletal problems, defects of the genitourinary tract; gastrointestinal tract; heart; eye and ears with hearing loss and acute myeloid leukemia
77
What is abnormal in hereditary nonpolyposis colorectal cancer/Lynch syndrome? What does it result in?
Autosomal Dominant!•Hereditary nonpolyposis colorectal cancer (HNPCC) = Lynch syndrome DNA mismatch repair abnormality leading to microsatellite instability associated with colorectal, endometrial, gastric, ovarian, ureteral, CNS, small bowel, hepatobiliary tract and skin cancers
78
Match the following genes to the inherited predisposition:RBp53p16/INK4A
RB Retinoblastomap53 Li-Fraumeni syndrome (various tumors)p16/INK4A Melanoma
79
Match the following genes to the inherited predisposition:APCNF1, NF2BRCA1, BRCA2
APCFamilial adenomatous polyposis/colon cancer NF1, NF2Neurofibromatosis 1 and 2 BRCA1, BRCA2Breast and ovarian tumors
80
Match the following genes to the inherited predisposition:MEN1, RETMSH2, MLH1, MSH6PTCH
MEN1, RETMultiple endocrine neoplasia 1 and 2 MSH2, MLH1, MSH6Hereditary nonpolyposis colon cancer PTCHNevoid basal cell carcinoma syndrome
81
Match the following genes to the inherited predisposition:PTENLKB1=STK11VHL
PTENCowden syndrome (epithelial cancers) LKB1=STK11Peutz-Jegher syndrome (epithelial cancers) VHLRenal cell carcinomas
