Neoplasia
Neoplasia
Neoplasia
Immune
Suppression?
Neoplasia?
Mutations?
A: The SAME 3 that are
ALWAYS blamed!
1) Chemicals
2) Radiation
3) Infectious
Pathogens
Induction of cancer by application of coal tar to the skin of rabbits (Yamagiwa. 1915)
CHEMICALS
Direct-acting agents Indirect-acting agents
• Weak
• E.g: polycyclic
carcinogens
hydrocarbons, aromatic
amines, azo dyes
Initiation/Promotion concept:
BOTH initiators AND promotors are needed
NEITHER can cause cancer by itself
OTHERS
Nitrosamine and amides (tar, nitrites)
Vinyl chloride angiosarcoma
Nickel
Chromium
Insecticides
Fungicides
PolyChlorinated Biphenyls (PCBs)
CHEMICAL CARCINOGENS:
PROMOTORS
HORMONES
PHORBOL ESTERS (TPA), activate kinase C
PHENOLS
DRUGS, many
UV light -sun
ionizing radiation
1. exposure from medical or occupational exposure,
2. nuclear plant accidents, and
3. atomic bomb detonations have produced a variety of forms of
malignant neoplasia.
Virus unable to complete its replicative cycle , viral genes essential for
completion of replication are interrupted during integration of viral DNA.
Thus, virus can remain in a latent state for years.
Viral genes transcribed early in the viral life cycle (early genes) are
important for cellular transformation, and are expressed in transformed
cells.
So what is an oncovirus?
Virus that causes cancer
Known oncoviruses are:
Hepatitis C
Hepatitis B
HTLV-1
HPV
HHV-8 (KSHV)
Merkel Cell Polyomavirus
EBV
VIRAL CARCINOGENESIS
HPV SCC
EBV Burkitt Lymphoma
HBV HepatoCellular Carcinoma (Hepatoma)
HTLV1 T-Cell Malignancies
KSHV Kaposi Sarcoma
Areas of the world with high mortality rates for HCC also
have high HBV infection rates
Cirrhosis is closely related with chronic HBV infection, at
least 80% of liver cancers occur in cirrhotic livers
Case control studies in all regions of the world have shown
that chronic HBV infection is much more common in HCC
cases than controls
› OR ranged from 5:1 to 65:1
Prospective studies of chronic HBV carriers have shown
very high relative risks for HCC
› 400 and 500 /100,000 compared with 5/100,000
› Prevention of HBV reduces risk of subsequent HCC
Effect of HPV proteins E6 and E7 on the cell cycle.
-Causes disease in
immunosuppressed patients;
asymptomatic in healthy people
-HIV/AIDS patients, transplant
patients, the elderly, chemo patients
-While this virus is typically
associated with AIDS patients in the
U.S., infection is widespread in sub-
Saharan Africa and there are more
cases of KS there
Sexually transmitted
-Infects lymphocytes, establishes latency
-Inflammation or some other stimulus ignites
the lytic cycle
-Inhibits p53 tumor suppressor protein
-Cell lysis allows virus to escape and infect
surrounding cells
Epstein-Barr Virus (EBV)
Some tissue types give rise to human cancers millions of times more often than other
tissue types. Although this has been recognized for more than a century, it has never been
explained. Here, we show that the lifetime risk of cancers of many different types is strongly
correlated (0.81) with the total number of divisions of the normal self-renewing cells
maintaining that tissue’s homeostasis. These results suggest that only a third of the
variation in cancer risk among tissues is attributable to environmental factors or inherited
predispositions. The majority is due to “bad luck,” that is, random mutations arising
during DNA replication in normal, noncancerous stem cells. This is important not only for
understanding the disease but also for designing strategies to limit the mortality it causes.
Diet 41%
Tobacco 24%
Infection 10%
Ultraviolet light 10%
Sexual factors 7%
Occupation 5%
Alcohol 3%
Pollution 1%
Medical procedures 1%
Ionizing radiation 1%
The data are taken from a review by Roush et al. And represent the
approximate midpoint of ranges derived from the data of Doll and Peto,
Higginson and Muir, and Wynder and Gori.
Thank you
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