Genetics and Cancer

Genetic Changes and Cancer

Cancer is a genetic diseaseóthat is, cancer is caused by certain changes to genes that control the way our cells function, especially how they grow and divide. These changes include mutations in the DNA that makes up our genes.

Genetic changes that increase cancer risk can be inherited from our parents if the changes are present in germ cells, which are the reproductive cells of the body (eggs and sperm). Such changes, called germline changes, are found in every cell of the offspring.

Cancer-causing genetic changes can also be acquired during oneís lifetime, as the result of errors that occur as cells divide during a personís lifetime or exposure to substances, such as certain chemicals in tobacco smoke, and radiation, such as ultraviolet rays from the sun, that damage DNA.

Genetic changes that occur after conception are called somatic (or acquired) changes. They can arise at any time during a personís life. The number of cells in the body that carry such changes depends on when the changes occur during a personís lifetime.

In general, cancer cells have more genetic changes than normal cells. But each personís cancer has a unique combination of genetic alterations. Some of these changes may be the result of cancer, rather than the cause. As the cancer continues to grow, additional changes will occur. Even within the same tumor, cancer cells may have different genetic changes.

Source: NCI (NIH)1

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Cancers that are not caused by inherited genetic mutations can sometimes appear to ďrun in families.Ē For example, a shared environment or lifestyle, such as tobacco use, can cause similar cancers to develop among family members. However, certain patterns in a familyósuch as the types of cancer that develop, other non-cancer conditions that are seen, and the ages at which cancer developsómay suggest the presence of a hereditary cancer syndrome.

Even if a cancer-predisposing mutation is present in a family, not everyone who inherits the mutation will necessarily develop cancer. Several factors influence the outcome in a given person with the mutation, including the pattern of inheritance of the cancer syndrome.

Here are examples of genes that can play a role in hereditary cancer syndromes.

For more genes that can play a role in hereditary cancer syndromes, see Genetic Testing for Hereditary Cancer Syndromes.

Source: NCI (NIH)2

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If someone in my family has cancer, am I likely to get cancer, too?

Not necessarily. Cancer is caused by harmful changes (mutations) in genes. Only about 5 to 10 percent of cancers are caused by harmful mutations that are inherited from a personís parents.

Source: NCI (NIH)3

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If no one in my family has had cancer, does that mean Iím risk-free?

No. Based on the most recent data, about 40 percent of men and women will be diagnosed with cancer at some point during their lives. Most cancers are caused by genetic changes that occur throughout a personís lifetime as a natural result of aging and exposure to environmental factors, such as tobacco smoke and radiation. Other factors, such as what kind of food you eat, how much you eat, and whether you exercise, may also influence your risk of developing cancer. For more information, see Cancer Causes and Risk Factors.

Source: NCI (NIH)4

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Certain genetic patterns or syndromes may increase the risk of a second cancer.

Some childhood cancer survivors may have an increased risk of developing a second cancer because they have a family history of cancer or an inherited cancer syndrome such as Li-Fraumeni syndrome. Problems with the way DNA is repaired in cells and the way anticancer drugs are used by the body may also affect the risk of second cancers.

Source: NCI (NIH)5

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Children of childhood cancer survivors are not affected by the parentís previous treatment for cancer.

The children of childhood cancer survivors do not appear to have an increased risk of birth defects, genetic disease, or cancer.

Source: NCI (NIH)6

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General Information About Childhood Cancer Genomics

Research teams from around the world have made remarkable progress in the past decade in elucidating the genomic landscape of most types of childhood cancer. A decade ago it was possible to hope that targetable oncogenes, such as activated tyrosine kinases, might be identified in a high percentage of childhood cancers. However, it is now clear that the genomic landscape of childhood cancer is highly varied, and in many cases is quite distinctive from that of the common adult cancers.

There are examples of genomic lesions that have provided immediate therapeutic direction, including the following:

For some cancers, the genomic findings have been highly illuminating in the identification of genomically defined subsets of patients within histologies that have distinctive biological features and distinctive clinical characteristics (particularly in terms of prognosis). In some instances, identification of these subtypes has resulted in early clinical translation as exemplified by the WNT subgroup of medulloblastoma. Because of its excellent outcome, the WNT subgroup will be studied separately in future medulloblastoma clinical trials so that reductions in therapy can be evaluated with the goal of maintaining favorable outcome while reducing long-term morbidity. However, the prognostic significance of the recurring genomic lesions for some other cancers remains to be defined.

Source: NCI (NIH)7

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Cancer occurs when cell division gets out of control. Usually, the timing of cell division is under strict constraint, involving a network of signals that work together to say when a cell can divide, how often it should happen and how errors can be fixed. Mutations in one or more of the nodes in this network can trigger cancer, be it through exposure to some environmental factor (e.g. tobacco smoke) or because of a genetic predisposition, or both. Usually, several cancer-promoting factors have to add up before a person will develop a malignant growth: with some exceptions, no one risk alone is sufficient.

The predominant mechanisms for the cancers featured here are (i) impairment of a DNA repair pathway (ii) the transformation of a normal gene into an oncogene and (iii) the malfunction of a tumor supressor gene.

Source: NCBI, Genes and Disease (NCBI/NIH)8

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While environmental factors can certainly contribute to a person's risk of cancer (e.g. smoking, diet, and exercise), most cancers have a genetic basis too. Literally hundreds of genes and proteins are involved in monitoring the process of cell division and DNA replication; a mutation in one or more of these genes or proteins can sometimes lead to uncontrolled cancerous growth.

Source: NCBI, Genes and Disease (NCBI/NIH)9

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The p53 gene like the Rb gene, is a tumor suppressor gene, i.e., its activity stops the formation of tumors.

If a person inherits only one functional copy of the p53 gene from their parents, they are predisposed to cancer and usually develop several independent tumors in a variety of tissues in early adulthood. This condition is rare, and is known as Li-Fraumeni syndrome. However, mutations in p53 are found in most tumor types, and so contribute to the complex network of molecular events leading to tumor formation.

The p53 gene has been mapped to chromosome 17. In the cell, p53 protein binds DNA, which in turn stimulates another gene to produce a protein called p21 that interacts with a cell division-stimulating protein (cdk2). When p21 is complexed with cdk2 the cell cannot pass through to the next stage of cell division. Mutant p53 can no longer bind DNA in an effective way, and as a consequence the p21 protein is not made available to act as the 'stop signal' for cell division. Thus cells divide uncontrollably, and form tumors.

Help with unraveling the molecular mechanisms of cancerous growth has come from the use of mice as models for human cancer, in which powerful 'gene knockout' techniques can be used. The amount of information that exists on all aspects of p53 normal function and mutant expression in human cancers is now vast, reflecting its key role in the pathogenesis of human cancers. It is clear that p53 is just one component of a network of events that culminate in tumor formation.

Source: NCBI, Genes and Disease (NCBI/NIH)10

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DNA repair genes: DNA repair genes, such as the mismatch repair (MMR) gene family, function normally to correct errors in cellular replication. When mutated these genes are unable to correct mutations in tumour suppressor genes or proto-oncogenes that may in turn lead to tumour formation. Mutations in the MMR genes (MSH2, MLH1 and MSH6) are known to cause familial (inherited) colorectal, breast and ovarian cancers.

Source: Australian Institute of Health and Welfare11

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mutation: A harmful change in "normalí DNA (the molecular building blocks of all cells). Some mutations are inherited and can be passed from parent to child. Others are acquired during a lifetime, the result of other factors such as age, tobacco use, infection with viruses, or exposure to ultraviolet radiation (sunlight). Mutations in genes that regulate cell division may lead to cancer.

There are four main gene types that increase the risk of cancer when mutated: tumour suppressor genes, proto-oncogenes, DNA repair genes and programmed death genes. These are described further below.

Source: Australian Institute of Health and Welfare12

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Cancer†begins with a change (mutation) in the structure of the DNA in cells, which can affect how they grow. This means cells grow and reproduce uncontrollably, producing a lump of tissue called a tumour.

Source: NHS Choices UK13

Genetic Testing for Cancer

genetic testing: The process of testing for the presence of particular genetic mutations. This form of testing is available to individuals at increased risk for inherited (familial) cancers, based on a strong family history of those cancers. The breast (and ovarian) cancer genes BRCA1 and BRCA2 are examples of genes with well-characterised mutations that can be "screenedí for in high-risk individuals. The presence of those mutated genes indicates an increased risk of developing breast or ovarian cancers. Similar to other screening tests, individuals receiving a positive test result may be referred for further investigation, or choose to undergo regular tests for pre-cancerous cells.

Source: Australian Institute of Health and Welfare14

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References

  1. Source: NCI (NIH): cancer.gov/ about-cancer/ causes-prevention/ genetics
  2. ibid.
  3. Source: NCI (NIH): cancer.gov/ about-cancer/ causes-prevention/ risk/ myths
  4. ibid.
  5. Source: NCI (NIH): cancer.gov/ types/ childhood-cancers/ late-effects-pdq
  6. ibid.
  7. Source: NCI (NIH): cancer.gov/ types/ childhood-cancers/ pediatric-genomics-hp-pdq
  8. Source: NCBI, Genes and Disease (NCBI/NIH): ncbi.nlm.nih.gov/ books/ NBK22177/ 
  9. Source: NCBI, Genes and Disease (NCBI/NIH): ncbi.nlm.nih.gov/ books/ NBK22218/ 
  10. Source: NCBI, Genes and Disease (NCBI/NIH): ncbi.nlm.nih.gov/ books/ NBK22268/ 
  11. Source: Australian Institute of Health and Welfare: aihw.gov.au/ reports-statistics/ health-conditions-disability-deaths/ cancer/ glossary
  12. ibid.
  13. Source: NHS Choices UK: nhs.uk/ conditions/ womb-cancer/ causes/ 
  14. Source: Australian Institute of Health and Welfare: aihw.gov.au/ reports-statistics/ health-conditions-disability-deaths/ cancer/ glossary

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Note: This site is for informational purposes only and is not medical advice. See your doctor or other qualified medical professional for all your medical needs.