What is HBOC Syndrome?
HBOC syndrome stands for ‘hereditary breast and ovarian cancer syndrome’. We define HBOC syndrome as any condition that causes a proven or obvious hereditary predisposition to higher-than-general-population rates of breast OR ovarian cancer and any of the related cancers. We often simplify the term by calling it ‘risky genes’.
The top-end average cancer risks for the most predominant HBOC syndrome cancers are shown below.
HBOC syndrome carriers are susceptible to some other types of cancer at lower rates, depending on the type of gene mutation they carry.
The terms ‘HBOC syndrome’ and ‘risky genes’ are often used synonymously with ‘carriers’, ‘high risk’, or ‘hereditary’ .
How does HBOC syndrome cause higher rates of cancer?
Our DNA tells a cell how to operate through our genetic code. When genes become broken, or mutated, it affects their ability to do their job properly. Some types of gene mutations can be passed down through the generations. When mutations are present in the genes responsible for our body’s ability to suppress tumours, they may significantly increase the risk of being diagnosed with cancer. The level of cancer risk is dependent on the gene affected and the type of mutation within that gene.
HBOC syndrome mutations reduce the body’s ability to ward off and fight cancer, so affected families experience cancer at a much higher rate than the general population, which may tend to be more aggressive and is often diagnosed at a younger age.
Not everyone who carries a mutation will develop cancer.
Both females and males can carry HBOC Syndrome. If an HBOC syndrome gene mutation has been found in either biological parent, a person has a 50% chance of having inherited it and the same 50% chance of passing it on to their children.
For more specific information about what a genetic mutation is and how it is passed down please see our booklet, Understanding Hereditary Breast & Ovarian Cancer Syndrome.
Actress Angelina Jolie Pitt gave HBOC syndrome awareness a huge boost when she shared her BRCA1 genetic status and subsequent preventative measures in the New York Times. Although most people have now heard of hereditary cancer, a follow-up study reported there is still a long way to go when it comes to education.
Learn more: Angelina Jolie preventative mastectomy
Learn more: Angelina Jolie Pitt preventative ovary and fallopian tube removal
Learn more: Angelina effect leaves public with inaccurate knowledge
How Common is HBOC Syndrome?
HBOC syndrome is far more common that most people realize. Unfortunately, the media, larger cancer organizations and medical professionals too often downplay the incidence or don’t report the whole story by referring to only one of the risky genes, as was was often the case regarding Angelina Jolie Pitt’s BRCA1 genetic status. This has created widespread misperception that HBOC syndrome is only a small problem.
An estimated 5-10% of all breast cancer and 10-15% of all ovarian cancer is estimated to be hereditary. Males are also susceptible to hereditary breast cancer, but at a lower rate than females. At least 5-10% of all prostate cancer is estimated to be hereditary. These percentages, widely accepted by the larger cancer organizations and the medical community, translate to about 250,000 to 450,000 Canadians with HBOC syndrome that have, or will be diagnosed with, hereditary breast, ovarian or prostate cancer. This does not include any of the other cancer diagnoses that carriers are susceptible to, nor does it include the percentage of carriers that aren’t expected to develop cancer, which would drive the actual number of HBOC Syndrome carriers even higher.
HBOC syndrome affects at least 3-5 times more
Canadians than multiple sclerosis
HBOC syndrome carriers, whether diagnosed with cancer or not, suffer deeply. Because there is no way to tell who will or won’t develop cancer, many carriers will still have endured drastic preventative measures, made tough decisions regarding fertility and lived their entire lives wondering if they will be next. Many carry the trauma of watching one or more loved ones die of hereditary cancer and they worry desperately for their living family members and their children.
Certain ethnic groups have a much higher chance of carrying HBOC syndrome. People of Ashkenazi (Eastern European) Jewish ancestry have a 2.5% (or 1 in 40) chance of having a mutated BRCA gene. Other ethnic and geographic populations with higher carrier incidence include the French Canadian, Norwegian, Dutch and Icelandic among others.
Learn More: Ovarian Cancer Canada
Learn More: HBOC Syndrome Cancer Incidence
Learn more: Centre for Jewish Genetics
Learn more: French Canadian, Polish Founder Gene
Learn more: Other Ethnic Groups
Discovery of HBOC Syndrome
HBOC syndrome was discovered in the mid 1990′s. The first genes that, if mutated, cause hereditary breast cancer were discovered by Dr. Mary-Claire King and her team. These genes were named BRCA1 and BRCA2, which stands for ‘breast cancer 1′ and ‘breast cancer 2′.
As time went on, researchers saw that mutations in BRCA1 and BRCA2 not only caused a high risk of breast cancer, but also ovarian and prostate cancer. Male BRCA carriers are susceptible to breast cancer too, but at a lower rate than females and both sexes are at a higher risk of pancreatic, skin and some other types of cancer at varying levels.
About one-third of hereditary ovarian cancer is estimated to be caused by BRCA mutations, leaving the balance to be caused by newly discovered or yet undiscovered gene mutations.
The two BRCA mutations are only responsible for less than half of the cases of hereditary breast cancer.
Researchers are still working to discover all the genes responsible for HBOC syndrome. This means a genetics professional may still deem a family as being high risk based on a variety of factors, even if genetic testing does not identify a specific genetic mutation.
Other HBOC Syndrome Genes
A number of new genes have been discovered that also cause hereditary breast and ovarian cancer. These include:
- ATM: The ATM gene helps repair damaged DNA. DNA carries genetic information in cells. Inheriting two abnormal copies of this gene causes the disease ataxia-telangiectasia, a rare disease that affects brain development. Inheriting one abnormal ATM gene has been linked to an increased rate of breast cancer in some families because the abnormal gene stops the cells from repairing damaged DNA.
- p53 (also called the TP53 gene): The p53 gene provides instructions to the body for making a protein that stops tumor growth. Inheriting an abnormal p53 gene causes Li-Fraumeni syndrome, a disorder that causes people to develop soft tissue cancers at a young age. People with this rare syndrome have a higher-than-average-risk of breast cancer and several other cancers, including leukemia, brain tumors, and sarcomas (cancer of the bones or connective tissue).
- CHEK2: The CHEK2 gene also provides instructions for making a protein that stops tumor growth. Li-Fraumeni syndrome also can be caused by an inherited abnormal CHEK2 gene. Even when an abnormal CHEK2 gene doesn’t cause Li-Fraumeni syndrome, it can double breast cancer risk.
- PTEN: The PTEN gene helps regulate cell growth. An abnormal PTEN gene causes Cowden syndrome, a rare disorder in which people have a higher risk of both benign (not cancer) and cancerous breast tumors, as well as growths in the digestive tract, thyroid, uterus, and ovaries.
- CDH1: The CDH1 gene makes a protein that helps cells bind together to form tissue. An abnormal CDH1 gene causes a rare type of stomach cancer at an early age. Women with an abnormal CDH1 gene also have an increased risk of invasive lobular breast cancer.
- PALB2: The PALB2 gene is called the partner and localizer of BRCA2. It provides instructions to make a protein that works with the BRCA2 protein to repair damaged DNA and stop tumor growth. Research published in 2014 found that an abnormal PALB2 gene increases breast cancer 5 to 9 times higher than average, almost as high as an abnormal BRCA1 or BRCA2 gene. Women with an abnormal PALB2 gene have a 14% risk of developing breast cancer by age 50 and a 35% risk of developing breast cancer by age 70. In comparison, women with an abnormal BRCA1 gene have a 50%-70% risk of developing breast cancer by age 70. Women with an abnormal BRCA2 gene have a 40%-60% risk of developing breast cancer by age 70.
Inheriting two abnormal PALB2 genes causes Fanconi anemia type N, which suppresses bone marrow function and leads to extremely low levels of red blood cells, white blood cells, and platelets. People with Fanconi anemia also have a higher risk of several other types of cancer, including kidney cancer and brain cancer.
- RINT1: The RINT1 gene, also called RAD50 interactor 1, helps regulate cell division. Besides breast cancer, an abnormal RINT1 gene is linked to Lynch-syndrome cancers: cancer of the colon, rectum, stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, ovaries, lining of the uterus, and skin.
- MRE11A: Along with the RAD50 and NBN genes, the MRE11A gene forms the MRN complex, which helps repair DNA damage in cells. An abnormal MRE11A gene is linked to ataxia-telangiectasia-like disorder, a rare disease that affects brain development. The disease also weakens the immune system and increases cancer risk.
- RAD50: Along with the MRE11A and NBN genes, the RAD50 gene forms the MRN complex, which helps repair DNA damage in cells. An abnormal RAD50 gene has been linked to a higher risk of breast cancer in some families because the abnormal gene stops the cells from repairing damaged DNA.
- NBN: Along with the MRE11A and RAD50 genes, the NBN gene forms the MRN complex, which helps repair DNA damage in cells. An abnormal NBN gene causes Nijmegen breakage syndrome, a condition that causes slow growth in infancy and early childhood. People with Nijmegen breakage syndrome are shorter than average, have a higher risk of several types of cancer, including breast cancer, and many other health problems. Of the three genes in the MRN complex, researchers think that an abnormal NBN has the strongest link to breast cancer.
- RECQL - Recently discovered in a Canadian-led study. The study found a strong link between mutations in RECQL and the onset of breast cancer among Polish and French-Canadian women.
Learn More: Genetic Variants
Learn More: Dr. Mary-Claire King
Learn More: MOVIE: the discovery of hereditary breast cancer. “Decoding Annie Parker”
Learn More: The real Annie Parker’s BOOK
Learn More: Discovery of RECQL
Learn More: Genetic Factors
Because a research cycle is about 20 years and the BRCA mutations were only discovered in the mid 1990′s, most of the research that drives recommendations today is based only on what is known about the BRCA mutations to date.
BRCA cancer risk data is generally reported in average ranges because not enough is known about the specific mutations within those genes to stratify cancer risk. When reading cancer risk tables and graphs, it is important to understand that a particular carrier’s personal cancer risk could fall above or below the ranges shown.
Personal cancer risk assessments are based not only on the average ranges accepted in that region, but on a host of other factors including family history. It is essential that cancer risk be assessed by a trained genetics professional.
Researchers still have a long way to go before cancer risk data for BRCA and the other genes that fall under HBOC syndrome have been established for each specific mutation. However, despite some discrepancies, all agree that carriers are at an much higher cancer risk than the general population.
The following examples illustrate some of the average cancer risk data differences:
Genetics and medical professionals will determine personal cancer risk based on a variety of factors.
Personal risk can fall above or below reported averages.
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