Center for Cancer Genetics
(Oncogenetics)
Run by Dr. Yael Goldberg and
Dr. Michal Sagi
The Clinic for Oncogenetic Counseling operates at Hadassah Ein Kerem on Mondays and Thursdays. The clinic was founded in 1995 and since then more than 4000 people have been seen there.
A special clinic for the genetics of gastrointestinal. tumors operates on Thursday mornings Hadassah Ein Kerem and once a month in Hadassah Mount Scopus.
The Oncogenetic Clinic sees patients who have been referred by oncologists, gynecologists, surgeons, gastroenterologists, nurses and community doctors, and men and women who come in on their own for counseling about breast, ovarian or uterine cancer, colorectal cancer, and other forms of cancer in their family.
The attending oncologists and other doctors are available for discussions later on if necessary regarding a follow-up plan and optional courses of action.
The available follow-up plans and treatment options are adapted to each individual according to their age, stage of life and personal history, and the patient’s
It should be emphasized that the genetic counseling and genetic tests are conducted under the strictest confidence. Results are given only to the patient and to no one else. Israel’s Confidentiality of Genetic Information Law states that an employer has no right to demand genetic information. The results are not stored in the hospital’s database.
Heredity and cancer – What is a genetic tendency towards developing cancer?
Our genes determine our development and characteristics, such as eye color, height, and so on. When a cell becomes malignant, changes occur in several of the genes causing it to grow and divide uncontrollably. In most cases, these changes take place in the cancerous cell itself and are not transmitted from one generation to another, that is, they are not hereditary. Indeed, most cases of cancer are not hereditary.
In rare cases, there is a genetic mutation that involves cancer risk, and this is hereditary. The individual that carries such a mutation is at greater risk of developing cancer. Since the development of a tumor depends on the appearance of other genetic changes, not every carrier will automatically develop a tumor, but the risk of getting cancer is greater among carriers. Changes to different genes involve increased risk for various tumors. The descendents of carriers have a 50% chance of inheriting the damaged gene from their parents.
To date several genes relating to the development of cancer have been discovered. The most common of these are related to breast cancer, ovarian cancer, uterine cancer and colorectal cancer. Generally speaking, carriers are recommended to have special monitoring and carry out suitable preventive measures, the goal of which is to reduce the incidence of illness and death.
When do you suspect an inherited tendency towards cancer?
It is important to emphasize that most cases of cancer are not hereditary in nature. Nevertheless, in families where there have been several cases of cancer, or in cases where the disease occurred at a relatively young age, there is a greater chance that this is a hereditary cancer. One may suspect a hereditary form of the disease if the number of cancer patients in the family is high, or if the age at which the disease appeared is relatively young (for example, in cases of breast or colorectal cancer – below age 50), and if several tumors appear in the same individual, for example, bilateral breast cancer, or uterine and colorectal cancer. Sometimes, especially in smaller families, there aren’t many cancer patients in the family, but the cancer may still be hereditary.
What genes are presently known?
We know about several genes in which mutations cause a greater risk for cancer. The most significant of these are: RET, PTEN, P53, MYH, APC, MLH1, MSH2, BRCA1, BRCA2.
Efforts to identify genes and genetic situations involving increased cancer risk are being conducted in cancer laboratories and clinics throughout the world. Our knowledge in the field is constantly on the rise. The most common cases where hereditary factors could be involved are:
Breast Cancer – We know that several genes are involved in a significantly increased risk for breast cancer, and a slightly greater risk for other cancers. The two main genes are called BRCA1 and BRCA2. Women who have mutations in these genes have a risk of up to 50%-80% of developing breast cancer by age 80, and an increased risk of developing ovarian cancer. Mutations in these genes are also involved in greater risk for developing other types of tumors (cancer of the pancreas, prostate, skin…), but in lower percentages. In the Ashkenazic population 3 common mutations have been identified (occurring in 2.5% of the population) in the BRCA1 / 2 genes. Mutations have also been identified in other population groups, but they are less common.
Colorectal cancer – Approximately 20%-30% of colorectal cancers are hereditary, and a genetic background has been identified in some of them. HNPCC (hereditary nonpolyposis colon cancer) Syndrome (or Lynch Syndrome) is the most common of all the genetic syndromes that lead to colorectal cancer. It is responsible for some 3%-5% of the cases of colorectal cancer. Among carriers, the risk of developing colorectal cancer can reach 80%, the risk for uterine cancer can reach 60%, and the risk of developing other tumors outside the gastrointestinal system like ovarian cancer, and tumors in the urinary tract and other organs (skin, brain,) may also be increased. HNPCC syndrome is caused by a mutation in genes relating to the repair of damage to the cell’s genetic material (DNA). Genetic clarification regarding the question of HNPCC is usually conducted in several stages: testing the DNA in the tumor, finding specific antibodies in the tumor, and then testing for mutations in the suspicious genes. Hadassah Hospital has recently set up a clinical and laboratory protocol for carrying out these clarifications. The laboratory test is relatively less expensive compared with the cost elsewhere.
Another gene that increases a person’s risk of colorectal cancer is APC (adenomatous polyposis coli), which is responsible for a rare syndrome known as FAP (familial adenomatous polyposis), in which a person can develop dozens and up to thousands of polyps in the colon with a high risk of cancer in the digestive tract.
Ovarian cancer – The two principal genes responsible are called BRCA1 and BRCA2. Women carried these mutations have an increased risk of developing ovarian cancer and a high risk of developing breast cancer. In the Ashkenazic population 3 common mutations have been identified (occurring in 2.5% of the population) in the BRCA1/2 genes. Mutations have also been identified in other population groups, but they are less common. It should be noted that roughly 50% of the Ashkenazic women who have had ovarian cancer will be found to have mutations in the BRCA genes.
Uterine cancer – In some cases this is caused by mutations in the genes that cause HNPCC (see above – Colorectal cancer).
Another important gene is P53. An inherited mutation in this gene is quite rare and increases the risk for a condition known as Li-Fraumeni syndrome, which is characterized by a greater risk for various tumors, such as brain tumors, sarcoma or breast cancer. To identify carriers with this genetic mutation it is important to adjust medications and avoid certain types of treatment.
As stated, we know of other genes whose mutations also entail greater risk for rare hereditary forms of cancer, such as melanoma, tumors of the endocrine glands, corneal tumors, etc.
What should I do if I am concerned about my family history?
For most people with a family history of cancer, the risk that there is a hereditary genetic component is not great. Nonetheless, even if the suspicion of a genetic component is not high, a history of cancer in the family slightly increases the chance of the disease occurring among other family members and at times, justifies greater monitoring, identification and prevention. We recommend updating and consulting with your family doctor about this.
We recommend clarifying the need for genetic counseling if your family history includes: several family members who were ill and/or the age at which they got sick was relatively young. For example: cases where several individuals in your family had breast cancer and/or ovarian cancer and/or colorectal cancer; or if the age at which these tumors were diagnosed was below 50; or if there was a case of bilateral breast cancer in women; or ovarian cancer in the case of Ashkenazi women.
Genetic counseling at Hadassah Hospital
Oncogenetic counseling is counseling regarding the genetic aspects of cancer. This counseling is given at Hadassah Hospital’s Oncogenetic Clinic by a staff composed of a geneticist, oncologist and a psychologist. By collecting complete information about cases of cancer in your family and analyzing the significance of your family history, the staff assesses the degree to which you may be at risk for the disease and the level to which a genetic-hereditary component may be suspected, and you can receive information about options for genetic testing. At the meeting the staff explains the significance of the test, and discusses the advantages and disadvantages of genetic clarifications.
During the counseling session the staff clarifies what the patient expects to achieve from the oncological counseling meeting and tries to attend to each person individually, according to their individual needs, test characteristics and consequences.
Genetic testing – What is recommended and what is the process?
Genetic testing is performed on the genetic material – the DNA – produced from blood that is taken through a simple blood test. Sometimes the test also involves a pathology sample of a tumor. The genetic material is saved for future tests at the family’s request.
It is preferable to perform the test using a sample from a person who is sick in order to identify the genetic change that exists in the family. If a change is identified in the test performed on the sick family member then it is proposed that the test be performed on health family members. In cases where it isn’t possible to test the sick family member, it may be time to consider testing the healthy family member, or it may be possible to produce DNA from a tumor sample from the sick person.
Testing for common changes in certain population groups, or changes that characterize a particular family, are relatively simple to perform, are low cost, and in most cases are funded by the Sick Funds and/or supplementary insurance coverage.
If no changes are found in this test, or if common changes are not found and a seriously hereditary condition is suspected, we will sometimes recommend a full scan of the suspicious genes or other complex genetic tests. These tests are often complicated and expensive, and therefore we recommend that they be carried out only in cases where a genetic-hereditary condition is greatly suspected, and then we can recommend follow-up measures that can reduce mortality.
Sometimes, even through suspicions were high and complex tests were carried out and a genetic component was not identified, this does not necessarily rule out its existence. This could be a case of a gene that hasn’t yet been identified. In these cases the family is referred for monitoring for early identification and prevention, in accordance with the level of risk determined on the basis of the family history.
What are the recommendations for monitoring and prevention in the event an increased risk for cancer is found?
Monitoring for early diagnosis and/or prevention of cancerous tumors is proposed to patients on the basis of their family history and/or the results of genetic testing. In any event, the individual himself must consider the monitoring that is recommended.
Below are general recommendations for populations defined as being at high risk. As stated, these recommendations must be adjusted for each individual and each case:
Breast: Doctor’s examination once every six months. Mammogram from age 35, or starting from 5 years younger than the youngest case of breast cancer diagnosed in your family. Recommend that women consider an ultrasound and MRI in certain cases, such as if they carry mutations in the BRCA genes. See: Additional information – Genetics of breast cancer.
Colon: In the case of increased risk for colorectal cancer, we recommend a colonoscopy starting from 5-10 years younger than the youngest case of colorectal cancer diagnosed in the family. If a specific hereditary condition is discovered, such as HNPCC or FAP, the age at which recommended monitoring should begin is even younger.
Ovaries: We recommend periodic monitoring, including a doctor’s examination, vaginal ultrasound examination, a testing for markers in the blood for ovarian tumors. However, since these are not effective for early diagnosis of ovarian cancer, we recommend prophylactic removal of the ovaries in certain cases.
Uterus: We recommend periodic monitoring, include a doctor’s examination and a vaginal ultrasound.
The impact of genetic information on medical treatment
Sometimes the genetic conditions has in impact on treating the disease itself, although in most cases the genetic condition effects only the recommendations regarding early detection and reducing risk.
Operations to reduce risk – These are recommended in certain cases following full genetic counseling on the basis of clinical, pathological and genetic data. For example, regarding a woman who has had breast cancer, her genetic condition may have an impact on her decision about the type of surgery she will have – the chance of a carrier who has had breast cancer to have a recurrence of the cancer is greater than in a woman who is not a carrier. This risk is greater for both the side in which the original cancer appeared, and the other side as well. However, at the time of the diagnosis, we must take into account the chance for recovery from the cancer that was diagnoses and then consider when is the best time for recommendations on prevention. Recommendations must take into account several factors, such as family history of cancer, type of tumor and its pathological characteristics, the age of the person when diagnosed with the disease, and the patient’s own preferences.
Removal of the ovaries is suggested to women around age 40 who carry mutations in the BRCA1 or BRCA2 genes. Preventive breast removal is also considered under certain circumstances. Partial removal of the colon is considered only in rare cases.
What are the advantages and disadvantages of genetic testing?
Genetic testing may help address the uncertainty in families that are known to be a greater risk for cancer based on family history. A positive result, that is, discovery of a genetic basis for the disease, may confirm that there is a greater risk for contracting cancer, but it also allows for beginning appropriate medical monitoring and/or preventive surgery. We hope that in the future, preventive drug treatment will also be a possibility.
A negative result may enable families to reassess their risk for the disease in certain cases, and take appropriate measures for proper monitoring.
The results of genetic testing of a particular individual also have significance for his family members and his children, and may be of special importance in the case of decisions regarding fertility and childbirth.
The staff is aware of the fact that there are those who prefer not to cope with the emotional burden of knowing about carriers, or they may prefer not to carry out the tests at certain stages of their lives. Therefore, discussions regarding oncogenetic testing are open to a discussion regarding this aspect of the testing process.
It is important to note that the existence of information regarding genetic carriers may have legal significance in terms of life insurance and medical insurance.
The Oncogenetic Clinic at Hadassah has an oncology nurse, working in conjunction with the Israel Cancer Society, whose job includes:
§ Coordinating clinic meetings.
§ Preliminary explanation about the significance of the test.
§ Preparing referrals for counseling meetings.
§ Emotional support and monitoring.
§ Coordinating between staff members and other professionals.
§ Designing and coordinating a follow-up plan together with the staff.
§ Education for early detection of the disease.
The oncology nurse helps those who have been referred to the Clinic, both when making decisions and afterwards, when they have received the test results.
To contact the Clinic and to make an appointment, call the Hadassah appointment Center at 02-5844111.
For additional information contact:
Ms. Michele Gordon
Oncogenetic Clinic Nurse
gordonm@hadassah.org.il
Tel.: 02-6777675, Mondays and Thursdays