Cancer is a complex group of diseases affecting a
wide range of cells and tissues. It is also a serious
health problem. In the United States, the lifetime
risk of developing cancer is one in two for males and one
in three for females. Mutations that alter the
expression of certain genes or their gene products are now
regarded as a common feature of all cancers. In most cancers,
these mutations occur in somatic cells and are not
passed on to future generations. However, in about 1% of
cancers, germ-line mutations are transmitted to offspring
and cause susceptibility to cancer. Studies of these mutations
provide insights into the origins of cancer.
Genomic alterations associated with cancer can involve
small-scale changes, such as single-nucleotide substitutions;
or large-scale events, such as chromosome
rearrangements, chromosome gain or loss, or even the
integration of viral genomes into chromosomal sites.
Large-scale genomic alterations are a common feature of
cancer; the majority of human tumors are characterized
by visible chromosomal changes.
It has been known for over 200 years that some types of
cancer run in families. An analysis of familiar cancers has
led to the identification of a class of genes called cancer
susceptibility genes that increase the risk of cancer. Variant
alleles of these susceptibility genes have an important
role in sporadic cancers as well as familial forms of cancer.
The likelihood that an individual will ultimately
develop cancer depends upon the particular mutant allele,
mutations in other genes, and environmental factors. These
variables may influence the age of onset and the severity
of the disease.
Cancer cells have two properties in common: (1) uncontrolled
growth, and (2) the ability to metastasize (spread)
from their original site to other locations in the body. Cell
division is the result of cells traversing the cell cycle; in
cancer cells, control over the cell cycle is lost, and cells
proliferate in an uncontrolled fashion. Investigations into
genetic control of the cell cycle are providing insights into
the origins of cancer.
Metastasis of cancer cells is controlled by gene products
that become localized on the cell surface, controlling how
these cells interact with the extracellular matrix and with other cells through cell-surface molecules. Loss of cell–cell contact allows cancer cells to leave the site of tumor
formation, spread throughout the body, and invade other
tissues. The study of metastasis is less well developed than
that of cell-cycle regulation, but research is beginning to
provide insights into the secondary events in tumor
progression.
We will consider the relationship between genes and
cancer, with emphasis on the relationship between the cell
cycle and genetic disorders. We will also examine how
mutations, chromosomal changes, and environmental
agents play a role in the development of cancer.
- 21.1 Cancer as a Disorder of the Cell Cycle
- Control of the Cell Cycle
- Cell Cycle Checkpoints
- 21.2 Genes that Control the Cell Cycle Are Involved
in Cancer
- 21.3 Tumor Suppressor Genes Repress Cell Division
- Retinoblastoma
- The Retinoblastoma Gene and the Cell Cycle
- Guardian of the Genome: p53
- Breast Cancer Genes
- 21.4 Proto-oncogenes Promote or Maintain
Cell Division
- Rous Sarcoma Virus and Oncogenes
- Origin of Viral Oncogenes
- Formation of Oncogenes
- 21.5 Colon Cancer as a Genetic Model of Cancer
- FAP and Colon Cancer
- Genomic Instability and HNPCC
- 21.6 The Path to Cancer Leads Through Gatekeeper
and Caretaker Genes
- 21.7 Chromosomal Translocations Are a Hallmark
of Leukemia
- 21.8 Environmental Factors Contribute to Cancer
- Hepatitis B and Cancer
- Environmental Agents
|
|
