Cancer Causing Genes

In the limelight: The genes of cancer

The “war against cancer” is, in actuality, a battle against a large group of sometimes very different conditions caused by differing agents.

Generally, cancer results from an altered balance between cell proliferation – growth and division – and cell death. A number of factors, including certain genes, viruses, chemicals or exposure to radiation, have been blamed for these normal activities gone awry.

Mutations in identifiable genes are, as a group, the latest of these factors to be discovered. They have also served as fuel for excitement over potential clues to ways that drugs may be designed to battle the varied disease.

Long known to occur repeatedly in families, cancer is one of the primary groups of diseases geneticists have fought long and hard to unravel at the molecular level. Research on organisms ranging from yeast to humans have identified three primary groups of genetic players which, when mutated, allow cells to grow at a rate more rapid than normal:

  • Oncogenes – Oncogenes promote cell proliferation and stop cell death, at times resulting in cancer.
  • Tumor suppressor genes – These protective genes normally limit the development and/or growth of tumors; when a tumor suppressor gene is mutated, it may fail to prevent a cancer from growing.
  • DNA mismatch repair genes – These genes maintain integrity of the genome and the fidelity of information transfer from one generation of cells to the next; loss of function of DNA mismatch repair genes could make a cell error-prone.

Cancer-associated genetic mutations may occur in an individual’s somatic, or body, cells such as breast tissue; certain breast tumors, for instance, are associated with non-inherited mutations in the HER2 gene.

Mutations in these important types of genes may also occur in an individual’s germ cells – eggs or sperm. In these cases, a mutation can be passed on from one generation to the next. Such mutations – called germ line or heritable mutations – are often associated with hereditary cancer. This group includes genes such as BRCA1, a gene associated with hereditary breast and ovarian cancer.

In the relatively short history of cancer genetics, the following ten genes stand out prominently for their research and/or clinical significance.


This tumor suppressor gene is named for a condition with which it is associated – familial adenomatous polyposis coli, a viciously premalignant disease with thousands of polyps contributing to inherited colorectal cancer in certain untreated gene carriers.


Mutations in this tumor suppressor gene, which encodes breast cancer type 1 susceptibility protein, are thought to be responsible for nearly half (45 percent) of inherited breast cancer (five percent of all breast cancer) cases and more than four in five cases of inherited breast and ovarian cancer.

A positive family history for breast cancer, which affects one in eight women during their lifetime, has been identified as major contributor to risk of development of the disease. This link is particularly striking for early- onset breast cancer.

BRCA1 mutation carriers are also four times as likely to develop colon cancer as their non-carrier counterparts; male carriers face a three-fold increased risk of prostate cancer.


This gene codes for a protein believed to play a role in the repair of DNA and/or exchange of DNA during cell division, or homologous recombination.

Believed to be responsible for some inherited breast cancer in women, BRCA2 is also linked with male breast cancer.


Research suggests that cyclin-dependent kinase 4, the protein encoded by the CDK4 gene, is involved in regulating the natural circadian rhythm of cells (cell cycle). Mutations in this gene have been shown to be involved in formation of certain non-hereditary cancers.


Mutations in the CMM1 gene are associated with familial malignant cutaneous melanoma.


Also referred to as NEU or ERBB2, this gene encodes for a protein which is essential component of a complex of molecules on the surface of cells called the neuregulin-receptor complex.

Associated with non-hereditary breast cancer, HER2 made headlines when biotechnology giant Genentech released its anti-cancer drug, Herceptin, which is used to treat patients whose breast tumors display an excess of HER2 protein.


Believed to play a role in fixing erroneous DNA replication, the MLH1 gene is associated with familial hereditary nonpolyposis colon cancer (HNPCC). HNPCC is one of the most common genetic diseases in the western world, accounting for up to ten percent of all colon cancers.


Named for a mutation first discovered in the bacterial counterpart of the human gene, the MSH2 gene is associated with a hereditary form of colon cancer (hereditary nonpolyposis colorectal cancer, HNPCC), which accounts for up to one in ten cases of the disease.

Alterations in the MSH2 and MLH1 genes are the most common mutations in families with multiple cases of HNPCC – together, they account for over 90 percent of mutations found in these individuals.

Like MLH1, the MSH2 protein is also involved in repairing errors during DNA replication.


Also called CDKN2, protein 16 has been shown to slow the growth and division of normal cells. Errors in the gene, presumably resulting in unbridled growth and division, are involved in tumor formation in a wide range of tissues, including skin (resulting in melanoma).


Normal protein 53 suppresses the development of many tumor types. It has been shown that to do so in a number of ways, including arresting the growth or even actually programming cells to die, depending on the physiological circumstances or cell type.

The protein is mutated or inactivated in about 60 percent of cancer cases; it is found in increased amounts in a wide variety of transformed cells.

For instance, variants in p53 cause a familial cancer syndrome called Li-fraumeni syndrome; in these families, the affected relatives develop a diverse set of malignancies including leukemia, breast carcinomas, sarcomas (bone tumors), and brain tumors at unusually early ages.

p53 mutations are also the cause of Barrett’s adenocarcinomas, a disease of the lower esophagus which develops as a complication in about one in ten patients with chronic untreated heartburn (gastroesophageal reflux disease).

Defects in p53 cause additional cancers, including head and neck squamous carcinomas.


One of the most important examples of a gene associated with hereditary cancer, Rb1 was used to describe the “two-hit theory” for hereditary cancers, which holds that in individuals carrying predisposing germ line mutations, cancer may occur as a result of an additional, non-inherited mutation.

Deletion or alteration of this protein results in the childhood eye cancer, retinoblastoma. This disease represents about two percent of all childhood malignancies

Although most cases of retinoblastoma appear sporadically, about one in five are transmitted as a genetic trait which may or may not show clinical symptoms.

The Rb1 protein is believed to regulate the expression of other genes, acting as a tumor suppressor.

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