Genetic Syndromes
What are genes and how do they work?
Genes are made of DNA and inherited (passed down) from parents to their children. The study of genes is called “genetics.” It is thought that humans have about 20,000 to 25,000 genes. Some genes make proteins that tell cells when to divide and when to stop dividing. These genes are often the ones that are affected by cancer.
The different cells in our body can use DNA in different ways. For example, liver cells use genes to make proteins that make bile, while cells in the brain (called neurons) use different genes in the same DNA to make neurotransmitters (chemical messengers in your body).
When a gene that helps with cell division is damaged (called a mutation in the DNA), cells may begin to divide even when they shouldn’t. This kind of mutation causes cells to divide and grow unchecked and out of control, causing cancer.
What is a genetic syndrome?
A genetic syndrome is a disease or group of diseases caused by a gene mutation. Genetic mutations can be found in members of a family, or they can happen in a person as a new, "de novo" mutation. DNA is inherited from both parents, carried on 23 chromosomes from each parent, for a total of 46 chromosomes. Two chromosomes are sex chromosomes, or "allosomes" (XX for women or XY for men). All the other chromosomes are called "autosomes."
A genetic syndrome that has a mutation in the DNA on an autosome is passed down in either an "autosomal dominant" or "autosomal recessive" pattern.
- An autosomal dominant syndrome needs only one parent's DNA to have the mutated gene. This mutated gene is "dominant" over the normal gene.
- An example of this is the BRCA1 mutation causing breast cancer. If you inherited a BRCA1 mutation from your parent, you are at higher risk for breast cancer. Because only one copy of the mutated gene is needed, autosomal dominant genetic syndromes often affect many people in the family.
- An autosomal recessive syndrome needs the DNA of both parents to have the mutated gene. If you inherit the mutated gene from both of your parents, you are at risk of having the syndrome. Because two copies of the mutated gene must be inherited, autosomal recessive diseases affect fewer members of a given family.
How does a genetic syndrome affect my cancer risk?
There are many types of genetic syndromes, but only a few are linked to a higher cancer risk. Most cancers are not related to genetic syndromes. Most cancers happen later in life, after years of DNA damage that mutates genes over time.
Genetic syndromes that cause cancer affect that gene from the beginning of life. These syndromes may then lead to cancer at a much younger age. While many families have members with cancer in old age, families with cancer-related genetic syndromes have a pattern of cancer in children and/or younger adults.
The genes affected in these syndromes tend to play a role in cell division, cell growth, DNA damage recognition, and DNA damage repair. Many of these genes make "tumor suppressor" proteins, whose normal job is to keep cells from dividing and growing out of control. When tumor suppressor genes are damaged, cells have the chance to divide and grow out of control, possibly forming tumors or cancer.
Genetic Syndromes Related to Cancer
(Table adapted from 1 Weitzel et al.)
Autosomal Dominant syndromes
Genetic Syndrome | |
| Hereditary breast and ovarian cancer (HPOC) |
|
| Hereditary prostate cancer |
|
| Neurofibromatosis 1 |
(see http://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1) |
| Neurofibromatosis 2 |
(see http://ghr.nlm.nih.gov/condition/neurofibromatosis-type-2) |
| Tuberous sclerosis |
(see http://ghr.nlm.nih.gov/condition/tuberous-sclerosis-complex) |
| Lynch syndrome/hereditary nonpolyposis colorectal cancer (HNPCC) |
|
| Familial adenomatous polyposis (FAP) |
(see http://ghr.nlm.nih.gov/condition/familial-adenomatous-polyposis) |
| Beckwith-Wiedemann syndrome |
(see http://ghr.nlm.nih.gov/condition/beckwith-wiedemann-syndrome) |
| Peutz-Jeghers syndrome |
(see http://ghr.nlm.nih.gov/condition/peutz-jeghers-syndrome) |
| Von Hippel-Lindau syndrome |
(see http://ghr.nlm.nih.gov/condition/von-hippel-lindau-syndrome) |
| Cowden syndrome |
|
| Carney complex |
|
| Li-Fraumeni syndrome |
|
| Costello syndrome/faciocutaeneoskeletal syndrome |
|
| Melanoma syndromes |
|
Multiple Endocrine Neoplasias (autosomal dominant)
Genetic Syndrome | |
| Multiple Endocrine Neoplasia (MEN) 1 |
(for all MEN subtypes, see http://ghr.nlm.nih.gov/condition/multiple-endocrine-neoplasia) |
| Multiple Endocrine Neoplasia 2A |
|
| Multiple Endocrine Neoplasia 2B (formerly 3) |
|
| Familial Medullary Thyroid Carcinoma (an MEN2 subtype) |
|
| Multiple Endocrine Neoplasia 4 |
|
Autosomal Recessive Syndromes
Genetic Syndrome | |
| Ataxia-telangiectasia |
(see http://ghr.nlm.nih.gov/condition/ataxia-telangiectasia) |
| Xeroderma pigmentosum |
|
This table shows the most common genetic syndromes related to cancer. The National Institute of Health's Genetics Information page has information about each syndrome mentioned above.
Resources for more information
Learn about genetic counseling and genetic testing.
Referencias
American Cancer Society. (2020). Family cancer syndromes. Retrieved from https://www.cancer.org/cancer/cancer-causes/genetics/family-cancer-syndromes.html
American Society of Clinical Oncology (ASCO). (2020). Li-Fraumeni Syndrome. Retrieved from https://www.cancer.net/cancer-types/li-fraumeni-syndrome
Daly, M. B., Pilarski, R., Axilbund, J. E., Berry, M., Buys, S. S., Crawford, B., ... & Klein, C. (2016). Genetic/familial high-risk assessment: breast and ovarian, version 2.2015. Journal of the National Comprehensive Cancer Network, 14(2), 153-162.
Gomes P, Pietrabissa G, Silva ER, Silva J, Matos PM, Costa ME, Bertuzzi V, Silva E, Neves MC, Sales CMD. Family Adjustment to Hereditary Cancer Syndromes: A Systematic Review. Int J Environ Res Public Health. 2022 Jan 30;19(3):1603. doi: 10.3390/ijerph19031603. PMID: 35162625; PMCID: PMC8834948.
Hampel, H., Bennett, R. L., Buchanan, A., Pearlman, R., & Wiesner, G. L. (2015). A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genetics in Medicine, 17(1), 70.
Imyanitov EN, Kuligina ES, Sokolenko AP, Suspitsin EN, Yanus GA, Iyevleva AG, Ivantsov AO, Aleksakhina SN. Hereditary cancer syndromes. World J Clin Oncol. 2023 Feb 24;14(2):40-68. doi: 10.5306/wjco.v14.i2.40. PMID: 36908677; PMCID: PMC9993141.
Kresak, J. L., & Walsh, M. (2016). Hereditary Cancer Syndromes in Children: Neurofibromatosis: A Review of NF1, NF2, and Schwannomatosis. Journal of pediatric genetics, 5(2), 98.
Mester, J., & Eng, C. (2015). Cowden syndrome: Recognizing and managing a not‐so‐rare hereditary cancer syndrome. Journal of surgical oncology, 111(1), 125-130.
McBride KA, Ballinger ML, Killick E, et al. Li-Fraumeni syndrome: cancer risk assessment and clinical management. Nature reviews. Clinical oncology. May 2014;11(5):260-271.
NIH: Genetics Home Reference. https://ghr.nlm.nih.gov/
Vasen, H. F., Tomlinson, I., & Castells, A. (2015). Clinical management of hereditary colorectal cancer syndromes. Nature Reviews Gastroenterology and Hepatology, 12(2), 88.
Weitzel JN, Blazer KR, Macdonald DJ, Culver JO, Offit K. Genetics, genomics, and cancer risk assessment: State of the Art and Future Directions in the Era of Personalized Medicine. CA: a cancer journal for clinicians. Aug 19 2011.