Hereditary Breast and Ovarian Cancer syndrome (HBOC)
Hereditary Breast and Ovarian cancer syndrome (HBOC), caused by changes (or mutations) in the BRCA1 and BRCA2 genes, is probably the most common cancer syndrome, and is the most likely hereditary cancer syndrome that people have heard of. HBOC causes an increase for not only breast and ovarian cancer, but also for prostate and pancreatic cancer. Changes in the BRCA2 gene also increase the risk for melanoma:
Cancer Risk for BRCA1 mutation carriers |
Cancer Risk for BRCA2 mutation carriers |
General Population Cancer Risk |
|||
Women |
Men |
Women |
Men |
||
Breast Cancer |
50-80% |
1-2% |
40-70% |
5-10% |
12% for women, 0.1% for men |
Ovarian Cancer |
24-40% |
N/A |
11-18% |
N/A |
1-2% for women |
Prostate Cancer |
N/A |
<30% |
N/A |
<39% |
15% for Caucasian men |
Pancreatic Cancer |
1-3% |
1-3% |
2-7% |
2-7% |
0.5% for both men and women |
BRCA1 hit the big time in 2013 when actress Angelina Jolie wrote an open letter in the New York Times about her process of undergoing genetic testing. After she was found to carry the same BRCA1 gene that caused her mother to pass away from ovarian cancer, she shared her decision to have a preventative double mastectomy (removal of breast tissue). Several important discussions arose out of Jolie’s disclosure, most importantly that women who are at this high risk for breast cancer have options. Jolie chose surgery. Some women choose to have more screening. How to integrate this information into your health is very personal decision, and one that your doctor or genetic counselor can help with.
These genes are inherited in an dominant pattern (see Autosomal Dominant Inheritance), so if someone is found to carry a mutation in BRCA1 or BRCA2, there is a 50% chance that they will pass that non-working gene down to each child that they have.
Lynch syndrome, or Hereditary Non-Polyposis Colorectal Cancer syndrome (HNPCC)
Lynch syndrome, also called Hereditary Non-Polyposis Colorectal Cancer syndrome (HNPCC), is a hereditary cancer syndrome that increases the risk for a diagnosis of colon cancer, as well as being diagnosed earlier in life than we would normally expect. Lynch syndrome also increases the risk for endometrial (uterine), gastric (stomach), ovarian, urinary tract, and some other rare types of cancer:
Type of Cancer |
Risk in the General Population |
Risk in people with Lynch syndrome |
Colon |
5.5% |
28-75% |
Endometrial (uterine) |
2.7% |
27-60% |
Gastric (stomach) |
<1% |
5-6% |
Ovarian |
1.6% |
6-12% |
Urinary tract |
<1% |
8-9% |
Small bowel, Brain/CNS, hepatobiliary tract, sebaceous carcinoma, keratoacanthomas |
<1% |
1-4% |
Changes in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes can cause Lynch syndrome. Anyone who has a family history of three or more relatives on the same side of the family who have any of the Lynch-related types of cancer should consider talking more with a genetic counselor about whether genetic testing for Lynch syndrome would be recommended.
Another red flag that there could lead to an increased risk for Lynch syndrome are if someone has a colon polyp, or growth, that is missing any of the genes that cause Lynch syndrome (MLH1, MSH2, MSH6, PMS2, and EPCAM). After the polyp is removed, it is sent to the pathology lab where they run tests on the tissue to see if they see any of the missing genes. If the pathology lab sees, for example, that MLH1 is missing from a patient’s colon tissue sample, there are two explanations: that the MLH1 gene was lost by chance (and not something the person was born with), or that the person was born missing one of their MLH1 genes. If the gene was lost by chance (sporadic), then it is likely just missing in that one part of the body. If someone is born missing one of their MLH1 genes, then every cell in their entire body would only have one working MLH1 gene, which is what causes the increased risk for cancer associated with Lynch syndrome.
If someone is found to have Lynch syndrome, there are many options available for early detection and prevention of the associated types of cancer. In the general population, screening for colon cancer is recommended every 10 years (if by colonoscopy) starting at the age of 50. In individuals with Lynch syndrome, the National Comprehensive Cancer Network (NCCN) recommends colon cancer screening starting at age 20-25 or 2-5 years prior to the earliest diagnosis of colon cancer in the family (whichever is earlier), and to repeat them every 1-2 years. There is not good screening for ovarian or endometrial cancer, so NCCN recommends that women at an increased risk for these types of cancer consider having a total hysterectomy and bilateral salpingo-oophorectomy (having your uterus, ovaries, and Fallopian tubes removed) once they are done planning a family. How to integrate this information into your health is very personal decision, and one that your doctor or genetic counselor can help with.
These genes are inherited in an dominant pattern (see Autosomal Dominant Inheritance), so if someone is found to carry a change in MLH1, MSH2, MSH6, PMS2, or EPCAM, there is a 50% chance that they will pass that non-working gene down to each child that they have.
Li-Fraumeni syndrome
Li-Fraumeni is a hereditary cancer syndrome that increases the risk for many different types of cancer, and generally these individuals are diagnosed at a particularly young age. The most common types of cancer seen in Li-Fraumeni are breast, brain, leukemia, and soft tissue and bone tumors (sarcomas), but there are many other forms of cancer associated with Li-Fraumeni syndrome. Furthermore, individuals with Li-Fraumeni are at a higher risk to get more than one type of cancer in their lifetime:
Risk of Any Cancer |
General Population Risk |
Li Fraumeni Risk |
By age 30 |
1% |
50% |
Lifetime |
41% |
90% |
Changes in the TP53 gene cause the increased risk for cancer associated with Li Fraumeni syndrome. Some red flags to look for in a family that may be at a high risk for Li Fraumeni syndrome are: people diagnosed with cancer (particularly sarcomas) before the age of 45, people who have had multiple diagnoses of cancer (likely at younger ages), or very early-onset breast cancer (before age 31).
If someone is found to have Li Fraumeni syndrome, there are several steps we can take to aid in early detection and prevention:
The TP53 gene is inherited in an dominant pattern (see Autosomal Dominant Inheritance), so if someone is found to carry a change in TP53, there is a 50% chance that they will pass that non-working gene down to each child that they have.