• Genetic testing is a type of medical test that identifies changes in genes or chromosomes, where your genetic information is stored.

• There are two types of genetic testing:

– Testing cancer cells for gene changes which is a type of testing used to look for gene changes that are present only in the cancer cells and are not inherited. These tests are not the same as the tests used to find out about hereditary cancer risk. These tests are useful to determine the type of cancer, how aggressive it is and the type of treatment the cancer patient should get.

– Predictive genetic testing which is a type of testing used to look for hereditary gene defects that might put an individual at a higher risk of getting certain types of cancer. It helps you learn more about your cancer risk to prevent the disease, improve the treatment course and ultimately increase the survival rates. It is available for certain types of cancers that might run in families such as: breast, ovarian, pancreatic, colon, and prostate cancers.

If you or any of your family members have any of the following, predictive genetic testing might be recommended for you:

· Cancer diagnosed at an unusual young age.

· More than one type of cancer developing in the same person.

· A rare cancer, such as breast cancer in a man or retinoblastoma (a cancer that begins in the retina of the eye).

· The lab test results of your cancer, such as your biopsy, show features that might be linked to a gene mutation.

· Cancer that has occurred in a set of paired organs, for example in both breasts or both kidneys.

· Many relatives on one side of the family had the same type of cancer or several first-degree relatives (mother, father, sisters, brothers, children) diagnosed with cancer.

· A physical finding that might be linked to a hereditary cancer, such as having a high number of polyps in the colon.

· A known genetic mutation was found in one or more of your family members who already had genetic testing.

If you are concerned about a pattern of cancer in your family, cancer you’ve had in the past, or other cancer risk factors, you may want to talk to a health care provider about whether genetic counseling and testing might be a good option for you.

Your doctor, geneticist or genetic counselor will take your detailed personal and family medical history with information on:

· Cancer history: the age when the disease was diagnosed and its course of progress.

· Your family pedigree: a sketch of your family tree highlighting the ages of the family members and their major diseases.

· It is usually done with a simple blood draw. You do not need to be fasting to perform the blood test.

· Sometimes a small sample of saliva and a swab sample from inside the mouth (from the inner side of the cheeks) is taken.

· Testing might also be done on relatives.

· Test results need several weeks to come out.

· Hereditary cancer Next Generation Sequencing panels analyze simultaneously multiple genes that are known to be associated with an increased cancer risk. This test is done when you do not have a previous positive cancer genetic test in the family.

· Targeted carrier screening is done when there is a known gene mutation in the family. It is used to screen for the presence of the familial gene defect only.

The most common genetic mutations for which testing is available are listed below with:

· Gene(s) that are mutated in each syndrome.

· Cancer types most often related with these syndromes.

Hereditary breast and ovarian cancer syndrome:

· Genes: BRCA1, BRCA2, PALB2, FANC, ATM

· Related cancer types: Female breast, ovarian, and other cancers: including prostate, pancreatic, and male breast cancer.

Li-Fraumeni syndrome

· Genes: TP53, CHEK2

· Related cancer types: Osteosarcoma (bone cancer), soft tissue sarcoma, breast cancer, leukemia, brain tumors, adrenocortical carcinoma (cancer of the adrenal glands), lung cancer and other cancers

Retinoblastoma

· Gene: RB1 · Related cancer types: Eye cancer (cancer of the retina), pinealoma (cancer of the pineal gland), osteosarcoma, melanoma, and soft tissue sarcoma

· Related cancer types: Eye cancer (cancer of the retina), pinealoma (cancer of the pineal gland), osteosarcoma, melanoma, and soft tissue sarcoma

Lynch syndrome (hereditary nonpolyposis colorectal cancer)

· Genes: MLH1, MSH2, MSH6, PMS2, EPCAM

· Related cancer types: Colorectal, endometrial, ovarian, renal pelvis, pancreatic, small intestine, liver and biliary tract, stomach, brain, and breast cancers

Diffuse gastric and lobular breast cancer syndrome

· Genes: CDH1

· Related cancer types: Breast, gastric and prostate cancers

Rhabdoid tumors

· Genes: SMARCB1

· Related cancer types: renal (kidney), brain and spinal cord.

Polyposis syndromes

· Gene: APC, MUTYH, SMAD4, BMPR1A

· Related cancer types: Colorectal cancer, multiple non-malignant colon polyps, and both non-cancerous (benign) and cancerous tumors in the small intestine, brain, stomach, bone, skin, and other tissues

Cowden syndrome (PTEN hamartoma tumor syndrome)

· Gene: PTEN

· Related cancer types: Breast, thyroid, endometrial (uterine lining) and other cancers

Von Hippel-Lindau syndrome

· Gene: VHL

· Related cancer types: Kidney cancer and multiple noncancerous tumors, including pheochromocytoma

Fore more information please visit the Department of Laboratory and Pathology Medicine

• Nada Assaf, MD Instructor

Department of Pathology and Laboratory Medicine

Medical Genetics division

Na167@aub.edu.lb, ext 5247

Dr Assaf is in charge of the Medical Genetics laboratory at the Department of Pathology and Laboratory Medicine at the American University of Beirut Medical Center. Her expertise involves genetic testing for constitutional (including prenatal) and cancer disorders such as chromosomal banding analysis (karyotype), Fluorescent in Situ Hybridization (FISH) and Next Generation Sequencing (NGS). She is the author of multiple articles published in peer-reviewed international journals, centered around hereditary cancers, and the genetic drivers of cancer.

Dr Assaf provides genetic counseling for patients and families with genetic disorders.

· If you have cancer, a positive test result indicates that this cancer might be a result of the genetic mutation you inherited. This will have consequences on your treatment and outcome.

· If you had genetic testing because a family member has an inherited cancer, a positive test result means you have an increased risk of cancer. Identifying your increased cancer risk at an early stage will help you plan to begin cancer prevention strategies to decrease your cancer risk as much as possible.

· The genetic counselor helps you define your medical family pedigree and determine which members should undergo genetic testing.

· You will be provided information about the implications of genetic testing.

· You will receive an explanation of your genetic test results to help you understand your family’s genetic condition and cancer risk.

· You will be given information on ways to lower your risk of developing cancer and detect cancer at its earliest stage when it is most treatable. This includes:

· more frequent screening tests at an earlier age: such as colonoscopy, mammography, etc.

· lifestyle changes: quitting smoking, limiting alcohol intake, eating a healthy diet, and exercising.

· taking preventive medications: such as Tamoxifen for the prevention of some types of breast cancer.

· preventive surgeries: removal of tissues or organs at risk, for example mastectomy or removal of ovaries for women with an elevated risk of developing breast or ovarian cancer.

· Not all genes associated with a hereditary type of cancer have been discovered yet. Genetic testing is limited to the genes that are known to be the cause of a higher cancer risk.

· A person with a family history of a hereditary type of cancer might develop cancer randomly, without it being caused by a genetic defect.

· Results detect the probability/risk of developing the disease, but they do not confirm that the disease will develop, or when, or at what stage it can appear.

· Results may show a genetic change that has never been seen before and that cannot be clearly considered as damaging. This would need more investigation, and it may take years to clarify the results.

· Results might not change or add to the usual medical recommendations for cancer prevention and screening.

· Talking about family history of cancer, a relative, or personal risk of getting the disease might be very stressful.

· Testing can create worry or uncertainty about the possibility of getting the disease in the future and the transmission of the risk to children.

· Testing might cause unease about communicating the information to other family members.

· It might cause concern about the costs of increased screening, medications or procedures or their effects on the insurance status.

·. A main issue is then to make sure the patient is appropriately informed before testing is done, and that he/she can understand the kind of results testing could produce so that he/she can decide if it is something they want to know.

·  This is why, it is extremely important to have an informed consent signed prior to genetic testing that may produce information that has implications on other members of the patient’s family.

·.  Genetic Counseling is a key player when such information is revealed and the service is also available at AUBMC through the Predictive Genetic Testing service. You can coordinate with your physician to get appropriate counseling with the Predictive Genetic Testing team.