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What is cancer? Name for a set of diseases that involve uncontrolled cell growth. More than
150 different types of cancer (most common: lung, skin, breast and colorectal)
Carcinogens my increase the risk of cancer by altering cellular metabolism or damaging DNA
directly in cells interfering biological processes, and inducing
the uncontrolled, malignant division.
Genes are found in the DNA in each cell. They control how cell works: how quickly it grows,
how often it divides and how long it lives.
All cancers begin when one or mre genes in a cell are mutated, or changed abnormal
protein or no protein at all (it can cause cells to multiply uncontrollably and become
cancerous).
Acquired mutations (most common cause of cancer). These occur from amage to genes during
a persons life. They are not passed from parent to child. Factors: tobacco, untraviolet(UV)
radiation, viruses and age. Example: lung cancer.
Germline mutations (5%-10% of all cancers). Are passed directly from a parent to a child (the
mutation can be found in every cell of a persons body, including the reproductive cells).
Examples: hereditary non-polyposis colon cancer, hereditary breast and ovarian cancer.
Mutations and cancer: mutations happen often, and the human body is normally able to
correct most of them. Extremely low mutation rate of eukaryotic cells (10-9 changes per
replication cycle)
Depending on where the gene mutates, a mutation can be: deleterious, beneficial, neutral or
lethal
May of the genes that contribute to the development of cancer fall into broad categories:
- Proto-oncogenes: genes involved in cell growth. Oncogenes turn a healthy cell into a
cancerous cell.
- Tumor suppressor genes: protective genes, genes stopping growth. Normally, they
limit cell growth by monitoring how quickly cells divide into new cells, repairing
mismatched DNA, and controlling when a cell dies.
- Genes preserving genomics stability: DNA repairing genes. These genes control DNA
repair (failure leads to accumulation of mutations).
Other mutations also damage genes that control apoptosis, control cell differentiation, inhibit
metastasis, control the cell cycle.
Proto-oncogenes
Mutations in proto-oncogenes give place to oncogenes. Oncogenes lead to signals that cause
uncontrolled growth. There are about 70 proto-oncogenes in our DNA. A few important
oncogenes are:
HER-2/neu: encodes for a cell surface receptor that can stimulate cell division. The HER-2/neu
gene is amplified in up to 30% of human breast cancers.
RAS: the Ras gene products are involved in kinase signaling pathways that ultimately control
transcription of genes, regulation cell growth and differentiation.
MYC: the Myc protein is a transcription factor and controls expression of several genes.
SRC: Src was the first oncogene ever discovered. The Src protein is a tyrosine kinase, which
regulates cell activity.
Normal genes whose absence can lead to cancer. Act to stop cell growth. Examples: BRCA1,
BRCA2 and p53
Germ line mutations in BRCA1 and BRCA2 genes increase a womans risk of developing
hereditary breast or ovarian cancers.
The most commonly mutated gene in people who have cancer is p53. In fact, more than 50%
of all cancers involve a missing or damaged p53gene. Most p53 mutations are acquired
mutations. Germline p53 mutations are rare.
Genes that ensure accurate copy during cell division of cell cycle. Mutations in DNA repair
genes lead to an increase mutation rate (hit of OG and TSG)
Mutator phenotype:
Four theories behind the gnesis of cncer? Or all of them in one? Untangling the roots of
cncer