STEPTRACKERGENERAL PRINCIPLES | PATHOLOGY + MICROBIOLOGY | HIGH-YIELD REVIEW

Carcinogens & Oncogenic Viruses

Exposure → cancer pairs: chemicals, radiation, viruses, bacteria and parasites — the occupation or region in the stem is the clue.

FOCUS ON
Vignettes hide the carcinogen in a job (dye worker, shipbuilder, PVC plant), a region (aflatoxin in Africa, Schistosoma in Egypt, liver fluke in East Asia) or a virus. HPV E6 targets p53 and E7 targets Rb.
AGENT
CANCER(S)
EXPOSURE · MECHANISM
Tobacco smoke
chemical
Lung, oral cavity, larynx, esophagus (SCC), bladder, kidney, pancreas, cervix, stomach
Polycyclic hydrocarbons, nitrosamines; #1 preventable cause
Aflatoxin
chemical
Hepatocellular carcinoma
Aspergillus on stored grain, peanuts; TP53 mutation; synergy with HBV
Aromatic amines
chemical
Urothelial carcinoma of bladder
Dye, rubber, textile, leather workers (β-naphthylamine, benzidine)
Asbestos
chemical
Bronchogenic carcinoma (most common), mesothelioma
Shipbuilding, roofing, plumbing, insulation
Vinyl chloride · arsenic
chemical
Angiosarcoma of liver (both); arsenic also skin SCC, lung
PVC manufacture · pesticides, contaminated well water
Benzene · alkylating agents
chemical
AML; cyclophosphamide also bladder carcinoma
Paint, rubber, gasoline · chemotherapy (acrolein → hemorrhagic cystitis)
Nitrosamines · alcohol
diet
Gastric (intestinal type) · esophageal SCC, HCC, oropharynx
Smoked/pickled foods (Japan, Korea)
Radiation
physical
Ionizing: AML, CML, papillary thyroid carcinoma, sarcoma · UV: BCC, SCC, melanoma · radon: lung
Ionizing → •OH and DNA breaks · UVB → pyrimidine dimers
HPV 16, 18
DNA virus
Cervical, anal, penile, oropharyngeal SCC
E6 → p53 degraded · E7 → Rb inactivated
EBV
DNA virus
Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, primary CNS lymphoma (AIDS), PTLD
Infects B cells via CD21; LMP-1 mimics CD40
HBV · HCV
hepatitis viruses
Hepatocellular carcinoma
Chronic inflammation and regeneration; HBV DNA integrates into the genome
HTLV-1 · HHV-8 · Merkel polyomavirus
other viruses
Adult T-cell leukemia/lymphoma · Kaposi sarcoma, primary effusion lymphoma · Merkel cell carcinoma
HTLV-1 Tax protein · HHV-8 in HIV/transplant patients
H pylori
bacterium
Gastric adenocarcinoma, MALT lymphoma
Chronic gastritis; early MALT lymphoma may regress after eradication
Schistosoma haematobium · Clonorchis sinensis
parasites
Squamous cell carcinoma of bladder · cholangiocarcinoma
Egypt, Africa · raw fish in East Asia

Mechanism — three roads to DNA damage

Direct mutagenChemicals, radiation
→
MutationOncogene or suppressor
→
Clone growsIf repair fails
Viral oncoproteinDisables p53 / Rb
→
Chronic inflammationHBV, HCV, H pylori, parasites
→
Repeated regenerationMore replication errors

Viral oncoproteins

VIRUS
PROTEIN
ACTION
HPV 16/18
E6
Marks p53 for degradation
HPV 16/18
E7
Binds Rb → E2F freed → S phase
EBV
LMP-1
Acts like active CD40 → B-cell growth
HTLV-1
Tax
Activates host growth genes (IL-2 pathway)
HBV
HBx, integration
Disrupts host genes, inactivates p53

How it's tested

COMMON CONFUSIONAsbestos causes more lung carcinoma than mesothelioma, but mesothelioma is the specific association.
THE TRAPBladder cancer can be urothelial (smoking, dyes, cyclophosphamide) or squamous (Schistosoma, chronic irritation). The exposure decides which.
YOUR APPROACHPull the occupation, diet, region or infection out of the stem, then match it to the organ and histologic type.

If you see… think…

Dye or rubber worker with painless hematuria → aromatic amines → urothelial carcinoma
Shipyard worker, pleural rind encasing the lung → mesothelioma (asbestos)
PVC plant worker with a liver mass → angiosarcoma (vinyl chloride)
HCC in sub-Saharan Africa, moldy stored grain → aflatoxin
Egyptian farmer, hematuria, squamous bladder cancer → Schistosoma haematobium
Cholangiocarcinoma after years of raw fish in East Asia → Clonorchis sinensis
Southern Chinese adult with nasopharyngeal mass and neck node → EBV
Caribbean or Japanese adult, hypercalcemia, "flower" T cells → HTLV-1 ATLL
HIV patient with purple skin plaques → HHV-8 Kaposi sarcoma
Papillary thyroid carcinoma after childhood neck radiation → ionizing radiation