Infections cause various malignancies like hepatic malignancy associated with Hepatitis B and C virus. This PPT will provide basic details regarding pathogenesis and mutations in infection induced malignancies.
3. Infections causing cancer
Infections account for 15 to 20% of all malignancies, worldwide.
Preventable cause of malignancy.
Viral infection – most common. It causes malignancy by
1. Production of Viral oncoproteins
2. By mutation of proto-oncogenes
3. By viral insertion
4. By chronic inflammation and tissue damage
7. Properties of oncogenic viruses
Causes chronic infection
Evade host immunity
Long latency between the infection and development of malignancy.
8. RNA virus
Human T cell Lymphotropic virus 1
(HTLV1)
Hepatitis C virus
DNA virus
Human Papilloma virus (HPV)
Epstein-Barr virus (EBV)
Kaposi Sarcoma Herpes virus (KSHV)
Hepatitis B virus
9. Human Papilloma Virus
HPV 6 and 11 – low malignant potential. Associated with Genital warts.
HPV 16 & 18 – high malignant potential. Causes squamous cell carcinoma of
cervix and Anogenital region.
20% of oropharyngeal malignancies are also associated with HPV infection.
By production of oncoproteins – E6 and E7.
E7 –binds to retinoblastoma protein (Rb)
E6 – binds to p53 and facilitates degradation of p53.
10.
11. E6 and E7 from HPV 16 &18 (high risk HPV) has highest affinity for p53 and Rb
protein.
HPV infection causes malignancy by,
1. Activation of cyclins
2. Inhibition of tumor suppressors ( p53, p21, p27)
3. Inhibition of apoptosis
13. EBV infects B cells via CD 21 receptor.
Latent Membrane Protein 1 ( LMP1) – EBV encoded gene and it promotes B- cell
proliferation by activating JAK/STAT and NF-kB pathways
Translocation between chromosome 8 and 14, which causes overexpression of
MYC proto oncogene.
Immunocompetent patients – asymptomatic or self limited disease.
In Immunosuppressive conditions such as concomitant malaria or other infections
– causes sustained B cell proliferation.
14.
15.
16. Kaposi sarcoma
Angio-proliferative spindle cell tumor –
derived from endothelial cells and
immune cells.
Human Herpes Virus 8 infection.
Lesions are seen in skin, oral mucosa,
lymph nodes, and visceral organs
17.
18. Types :
1. Classic – occurs as sporadic infection, progressive over 10 to 15 years.
2. Endemic - common in African countries
3. Epidemic or AIDS related ( CD4 <500cells/cu.mm)
4. Iatrogenic – organ transplant related
22. Mechanism
Activation of NF-kB pathway (By mediators from immune cells) – inhibits
apoptosis
Chronic inflammation and tissue damage
Production of reactive oxygen species
Accumulation of mutation and will result in malignant proliferation
23.
24. Helicobacter pylori
Gastric adenocarcinoma
Gastric MALToma
CagA gene is injected into the gastric epithial cells and causes unregulated growth
signals.
Pathology:
1. Chronic inflammation and tissue damage
2. Increased epithelial cell proliferation
28. Multiple Endocrine Neoplasia
MEN 1 syndrome or Wermer syndrome MEN 2 syndrome or Sipple’s syndrome
Mutation:
MEN 1 gene on chromosome 11 RET proto oncogene mutation
1. Pituitary adenoma
2. Hyperparathyroidism
3. Pancreatic neuroendocrine tumours
1. Medullary carcinoma thyroid
2. Pheochromocytoma
3. Parathyroid tumors
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32.
33. Summary
HPV – causes cervical cancer. Produces oncoproteins E6 and E7 which binds to
p53 and Rb gene.
EBV – Various B cell lymphomas, Nasopharyngeal carcinoma
Hepatitis B and Hepatitis C – causes chronic hepatitis and cirrhosis. Malignancy
occurs in untreated patients as a result of chronic inflammation.
HTLV1 – retrovirus (like HIV) infects CD4 cells and causes T cell leukemia
34. H. Pylori – CagA gene. Causes gastric adenocarcinoma and MALToma
MEN syndromes – MEN 1 ( chromosome 11) and MEN 2 – RET proto oncogene.
BRCA 1& 2 – breast cancer
Rb gene – retinoblastoma
APC gene – Familial adenomatous polyps or colon cancer