The Genetics of Cancer 2 --- Cancer Genes
IV. Types of
cancer genes
1. Oncogenes
•Proto-oncogenes
are normal versions of genes which promote cell division.
•Expression
at
the wrong time or in the wrong cell type leads to cell division and
cancer.
•Proto-oncogenes
are called oncogenes in their mutated form.
•One
copy of an
oncogenic mutation is sufficient to promote cell division.
Oncogenes:
overexpression of a normal function
•Viruses
integrated next to
a proto-oncogene can cause transcription when the virus is transcribed.
2.
•Translocation
of chr 9 to chr 22 fuses the abl oncogene and the bcr region.
•The
abl protein
is a tyrosine kinase enzyme.
•The
bcr-abl
fusion protein is active for too long leading to extra cell division in
white
blood cells, a cancer called leukemia.
3. Tumor
suppressor genes
•Cancer
can be
caused by loss of genes that inhibit cell division.
•Tumor
suppressor genes normally stop a cell from dividing.
•Mutations
of
both copies of a tumor suppressor gene is usually required to allow
cell
division.
4. p53 coordinates
cell cycle regulation
•p53
acts as a
cell cycle protein which determines if a cell has repaired DNA damage. If damage cannot be repaired, p53 can induce
apoptosis.
•More
that 50%
of human cancers involve an abnormal p53 gene.
•Rare
inherited
mutations in the p53 gene cause a disease called Li-Fraumeni syndrome
in which
family members have many different types of cancer at early ages.
5. BRCA1, a breast
cancer susceptibility gene
•Within
families a mutation
in BRCA1 leads to breast cancer susceptibility, inherited as a dominant
trait.
•One
mutation in the BRCA1
gene is inherited.
•Tumors
in people acquire a
second mutation in the normal allele of BRCA1.
•Lack
of any functional
BRCA1 leads to cell division.
•At
the level of the cell,
BRCA1 acts in a recessive manner.
Complexities in genetic counseling for familial
breast
cancer
•Many
mutations
are known but not all are associated with disease. (Some are
polymorphisms.)
•Individual
with
inherited predisposition and individuals with sporadic cancer can be
found
within the same family.
•BRCA1
and BRCA2
are not fully penetrant. Occasionally
individuals with a mutation do not develop cancer.
6. Multiple genes
contribute to cancer progression
7. Environment
impacts cancer
Exposure to carcinogens
•Carcinogens
in
tobacco smoke are correlated with lung cancer incidence.
Exposure to radiation
•Burns
from
overexposure to sunlight can cause skin cancer.
Variation in diet
•Fatty
diets are
correlated with increased estrogen and increased breast cancer.
Cruciferous vegetables can lower cancer risk
8. Methods for
evaluating environmental impacts of cancer
Population studies compare incidence of a
cancer trait
among different populations.
Case-control studies compare individuals with
cancer to
healthy individuals matched for characteristics such as age, sex, and
ethnic
background.
Prospective studies follow the outcome of
individuals
placed in two or more groups who have different treatments, conditions,
or
procedures.