cancer cells are characterized by changes in
ex: Down syndrome (trisomy 21) – upwards of 20X more likely to develop
leukemia
leukemia
extra copies of genes on 21 chromosome may predispose to cancer
which genes?
chromosome instability
instability induces chromosome breaks, gaps, rearrangements and translocations
ex: Bloom syndrome –
ex: Fanconi anemia –
fragile sites are structural features of chromosomes
17 sites have been identified in the human genome
not much is known about the molecular nature
ex: a fragile site near the tip of the long arm of the X chromosome
ex: site on chromosome 3
short arm of chromosome 3 is thought to carry one or more genes
in lung cancer cells obtained from tumors or laboratory-grown cell lines,
over 75% of samples have a loss of one or both alleles of a gene known as
FHIT
it is thought that such a fragile site is more susceptible to breakage
since it has been determined that cigarette smoke contains compounds
that interfere with DNA replication
tempting to speculate that the common thread in all these chromosome instability syndromes is the inheritance of a germ-line mutation
subsequent mutagenic events like exposure to environmental radiation from UV-light or X-rays
numerous types of leukemia
in one of the first discovered, patients with chronic myelogenous leukemia (CML)
however, it was later discovered that instead of a deletion there was a reciprocal translocation
this translocation is very important because instead of just shuffling pieces of chromosomes
the new gene consists of a sequence of DNA from the 22nd chromosome known as the breakage cluster region (bcr) which is fused to the proto-oncogene c-abl sequences and this fusion gene, brc-abl
this hybrid gene is transcribed and the message is translated
the finding that certain forms of cancer are consistently associated with specific chromosomal abnormalities suggests
strong evidence that chromosome rearrangements are not by-products of the malignant condition
found that the chromosomal locations of normal proto-oncogenes are at or very near the breakpoints of translocations
Cancer and the Environment
Research into the relationship between the environment and cancer has been conducted for over 50 yrs
this research or epidemiology
provides correlations between factors and the existence of a disease
ex: widespread geographic variations in cancer cases and mortality
many cases of cancer in the US are thought to be related to
estimates indicate that at least 50% of all cancer can be attributed to
what about the relationship between occupation and cancer?
occupational exposure to some chemicals is known to cause cancer
ex: in the case of retinoblastoma, if someone inherits two normal alleles of the RB
gene, then 2 separate mutations must occur
because of the time required to acquire 2 separate mutations
same thing is true of other occupational hazards like exposure to vinyl chloride
(which is used in the manufacturing of plastic) or asbestos and also
environmental factors like cigarette smoke, UV-light, and diet and nutrition
so there are lots of possible agents that can cause cancer
need some way to test the carcinogenic potential
and then relate this back to its mutagenic potential
carcinogens are usually either a chemical or a form of radiation
ex:
ex:
some of the alterations induced by radiation may promote transcription of genes
one important characteristic of radiation-induced cancer is the potentially long
delay
radon gas –
studies suggest that radon exposure might be the primary cause of
information from EPA website