Genetic Syndromes

Autor: Michael LaRiviere, MD
Última Vez Revisión: 6 de abril de 2018

What are genes and how do they function?

A gene is a sequence of DNA that codes for a specific protein. Cells have enzymes that read genes from the DNA and produce all of the proteins the cell needs. Essentially, DNA is like a cookbook, and all cells have the same cookbook. A gene is like a recipe, and the protein that the gene codes for is like the cooked meal. Different types of cells all contain the same DNA, but use that DNA to produce different types of proteins. For instance, liver cells use genes to make proteins for bile production, whereas neurons in the brain use different genes in the same DNA to make neurotransmitters.

Certain genes make proteins that tell cells when to divide and when to stop dividing; these are often the genes that are disrupted in cancer. In an adult, certain cells continue dividing rapidly, while other cells stop dividing. Skin cells, for instance, continue to divide throughout life. Neurons, on the other hand, stop dividing or divide very slowly.

When a gene involved in cell division is disrupted – a mutation in the DNA – cells may begin to divide inappropriately. If a critical cell division gene has a mutation, or if mutations in enough genes come about, cells can divide and grow unchecked, and this is how a cancer develops.

What is a genetic syndrome?

A genetic syndrome is a disease caused by a gene mutation. Genetic mutations may run in families, or they may arise in an individual as a new, "de novo" mutation. DNA is inherited from both parents, carried on twenty-three chromosomes from each parent, for a total of forty-six chromosomes. Two chromosomes are sex chromosomes, or "allosomes" – XX for women or XY for men. The remaining chromosomes are called "autosomes."

A genetic syndrome with a mutation in the DNA on an autosome is transmitted in either an "autosomal dominant" or "autosomal recessive" pattern. An autosomal dominant syndrome requires only one parent's copy of the gene to harbor a mutation – that mutated gene is "dominant" over the normal gene. An example of this is the BRCA1 mutation causing breast cancer – if a woman inherited a BRCA1 mutation from her parent, she is at increased risk for breast cancer herself. Because only one copy of the mutated gene is needed, autosomal dominant genetic syndromes typically affect many people in a given family.

On the other hand, an autosomal recessive syndrome requires both parents' DNA to contain the mutated gene. If an individual inherits the mutated gene from both parents, he/she is at risk of developing 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 relate to cancer?

While there are a number of genetic syndromes – Tay Sachs disease, Huntington's Disease, hemophilia, to name a few – only a few genetic syndromes are associated with increased cancer risk. The vast majority of cancers are not related to genetic syndromes. Most cancers arise later in life, after decades of DNA damage that ultimately mutates critical genes.

Cancer-related genetic syndromes, on the other hand, affect a critical gene from the very beginning of life. These syndromes therefore lead to cancer at a much earlier 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 produce "tumor suppressor" proteins, whose normal function is to prevent uncontrolled division and growth. When tumor suppressor genes are damaged, cells gain the ability to divide unchecked, potentially forming tumors or cancer.

Genetic Syndromes Related to Cancer

(Table adapted from 1 Weitzel et al.)

Autosomal dominant syndromes

Genetic Syndrome
Gene: Associated Cancer(s)
Prevalence/Additional Information

Hereditary breast and ovarian cancer

  • BRCA1: breast cancer, ovarian cancer
  • BRCA2: prostate cancer, pancreatic cancer, melanoma
  • 1/400, higher in Ashkenazi Jewish and other ethnicities2

Hereditary prostate cancer

  • HPC1, HPCX, HPC2/ELAC2, PCAP, PCBC, PRCA
  • Estimated at approximately 10% of prostate cancers3, 4

Neurofibromatosis 1

  • NF1: neurofibrosarcoma, pheochromocytoma, optic glioma, meningioma
  • 1/3,000-4,000

(see http://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1)

Neurofibromatosis 2

  • NF2: vestibular schwannoma/acoustic neuroma
  • 1/33,000

(see http://ghr.nlm.nih.gov/condition/neurofibromatosis-type-2)

Tuberous sclerosis

  • TSC1, TSC2: renal cancer, renal angiomyolipomas, myocardial rhabdomyoma, ependymoma, astrocytoma; benign tumors
  • 1/6,000

(see http://ghr.nlm.nih.gov/condition/tuberous-sclerosis-complex)

Lynch syndrome/hereditary nonpolyposis colorectal cancer

  • MLH1, MSH2, MSH6, PMS2, EPCAM: colorectal cancer, endometrial cancer, gastric cancer, hepatobiliary cancer, pancreatic cancer, small bowel cancer, ovarian cancer, renal cancer, ureteral cancer; earlier development of benign colon polyps
  • 1/4,200-7,000 colorectal cancers
  • Turcot syndrome: glioblastoma

(see http://ghr.nlm.nih.gov/condition/lynch-syndrome)

Familial adenomatous polyposis

  • APC: colorectal cancer, gastric cancer, duodenal cancer, ampullary cancer
  • 1/7,000-22,000
  • Turcot syndrome: medulloblastoma

(see http://ghr.nlm.nih.gov/condition/familial-adenomatous-polyposis)

Beckwith-Wiedemann syndrome

  • CDKN1C, NSD1: Wilms tumor, hepatoblastoma, adrenal carcinoma, gonadoblastoma
  • At least 1/12,000

(see http://ghr.nlm.nih.gov/condition/beckwith-wiedemann-syndrome)

Peutz-Jeghers syndrome

  • STK11/LKB1: colorectal cancer, small bowel cancer, pancreatic cancer, breast cancer, ovarian cancer
  • 1/25,000-300,000

(see http://ghr.nlm.nih.gov/condition/peutz-jeghers-syndrome)

Von Hippel-Lindau syndrome

  • VHL: retinal and central nervous system hemangioblastomas, renal cell cancer, pheochromocytoma, endolymphatic sac tumors
  • 1/36,000

(see http://ghr.nlm.nih.gov/condition/von-hippel-lindau-syndrome)

Cowden syndrome

  • PTEN, KLLN, SDHB, SDHD (AD): breast cancer, thyroid cancer, endometrial cancer
  • 1/200,000

(see http://ghr.nlm.nih.gov/condition/cowden-syndrome)

Carney complex

  • PRKAR1A: subcutaneous myxoid tumors, adrenocortical nodular hyperplasia, testicular cancer, atrial myxoma, pituitary adenoma, breast fibroadenomas, thyroid cancer, schwannoma
  • 750 individuals

(see http://ghr.nlm.nih.gov/condition/carney-complex)

Li-Fraumeni syndrome

  • p53: breast cancer, sarcomas, brain tumors5, adrenocortical carcinoma, leukemia
  • 400 inidividuals

(see http://ghr.nlm.nih.gov/condition/li-fraumeni-syndrome)

Costello syndrome/faciocutaeneoskeletal syndrome

  • HRAS: epithelioma, bladder cancer, rhabdomyosarcoma, vestibular schwannoma/acoustic neuroma
  • 1/300,000-1,250,000, 200-300 individuals

(see http://ghr.nlm.nih.gov/condition/costello-syndrome)

Melanoma syndromes

  • p16/CDNK2, CDK4, CMM: malignant melanoma

Multiple Endocrine Neoplasias (autosomal dominant)

Genetic Syndrome
Gene: Associated Cancer(s)
Prevalence/Additional Information

Multiple Endocrine Neoplasia (MEN) 1

  • MEN1: parathyroid adenoma, pituitary adenoma, pancreatic islet cell tumor, less commonly other tumors6
  • 1/30,000

(for all MEN subtypes, see http://ghr.nlm.nih.gov/condition/multiple-endocrine-neoplasia)

Multiple Endocrine Neoplasia 2A

  • RET: medullary thyroid cancer, pheochromocytoma, parathyroid adenoma
  • 1/37,000

Multiple Endocrine Neoplasia 2B
(formerly 3)

  • RET: medullary thyroid cancer, pheochromocytoma, mucosal neuromas6
  • 1/700,000

Familial Medullary Thyroid Carcinoma
(an MEN2 subtype)

  • Medullary thyroid cancer

Multiple Endocrine Neoplasia 4

  • CDKN1B: parathyroid adenoma, pituitary adenoma, other tumors
  • Prevalence unknown, but rare

Autosomal Recessive Syndromes

Genetic Syndrome
Gene: Associated Cancer(s)
Prevalence/Additional Information

Ataxia-telangiectasia

  • ATM: leukemia, lymphoma
  • 1/40,000-100,000

(see http://ghr.nlm.nih.gov/condition/ataxia-telangiectasia)

Xeroderma pigmentosum

  • XPA-G, POLH: skin cancers, melanoma, leukemia
  • 1/1,000,000; higher in Japan, North Africa, and the Middle East7

Resources for more information

Learn about genetic counseling and genetic testing

The National Institute of Health's Genetics Information page has lots of information about each syndrome mentioned above.

Referencias

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.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.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.

Palabras clave

Haga clic en cualquiera de estos términos para más artículos relacionados

A
B
C
D
E
F
G
H
I
J
K
L
M
N
O
P
R
S
T
U
V
X
Y
Z
#
 
A
B
C
E
F
G
H
K
L
M
N
O
P
R
S
T
U
V
 
 
Manténgase informado con las última información de OncoLink!   Suscribirse a los boletines electronico de OncoLink
Ver nuestros archivos de boletines