Part 2 – Genetic Testing and the “Jolie Effect”

We mentioned in Part 1 of our series of articles on “Genes – Do they place you at a HIGH risk of cancer?” that there are many factors that could increase your risk of developing cancer. One of those ways is by inheriting a mutated (damaged) cancer gene. One of the 21st century’s proudest scientific achievements has been the mapping of the human genome, which was officially declared complete in April 2003. Scientists have now isolated numerous mutated cancer-causing genes, which are inherited and passed on through families. Of course, we know that cancer is such a common disease, and it shouldn’t be any surprise that there is at least a few members within several generations of a family who have had some form of cancer. But, before you decide that cancer just runs in your family, it would be important to firstly consider some things. Ask yourself some pertinent questions. For each case of cancer in your family:- •    Who is affected? •    How are you related to that person? •    What type of cancer is it? •    Is it a rare form of cancer? •    How old was this person when they were diagnosed? •    Did this person have more than one type of cancer? •    Did this person smoke, drink alcohol excessively or have any other known risk factors?  

Cancer-Related Genetic Testing

There are certain “flags” which may alert your doctor to the likelihood you could be affected by a family-related cancer syndrome, and genetic testing and counselling could be considered, e.g.: •    There are many cases of a rare or uncommon type of cancer, such as kidney cancer. •    There are cancers occurring at younger ages than is commonly seen, such as colon cancer in a 20 year old. •    There is more than one type of cancer occurring in one family member, such as a female with breast and ovarian cancer. •    There are cancers occurring in both sets of organs, such as both eyes, both kidneys, or both breasts. •    There is more than one childhood cancer in a set of siblings, such as sarcoma in both a brother and sister. •    Cancer which has occurred in the sex not usually affected, such as a male with breast cancer. •    There are several close blood relatives that have the same type of cancer, such as a mother, daughter, and sisters with breast cancer. Your doctor may suggest you see a professional genetic counsellor who can more thoroughly explain the risks and benefits as well as any limitations in the genetic testing itself. In some instances, it may not be advisable or be necessary. If you decide to go ahead with genetic testing, a sample of cells from your cheek, or skin, or saliva or a blood test can be taken and then sent off to a specialised pathologist who deals with genetic testing. It may take several weeks or longer for those results to become available to you, which should then be discussed with your doctor or genetic counsellor. The following list includes some of the more commonly inherited cancer syndromes that genetic testing is currently available for. Hereditary breast and ovarian cancer syndrome: Related Cancers: Female breast cancer, ovarian cancer, and other cancers including prostate, pancreatic and male breast cancer. Genes:  BRCA1, BRCA2 Li-Fraumeni Syndrome: Related Cancers: Breast, soft tissue sarcoma, Osteosarcoma (bone), leukemia, brain tumours, adrenocortical carcinoma (adrenal glands), and other cancers. Gene:  TP53 Lynch Syndrome – Hereditary non-polyposis colorectal cancer: Related Cancers: Colorectal, endometrial, ovarian, renal pelvis, pancreatic, small intestine, liver and biliary tract (bile ducts), stomach, brain, and breast cancers. Genes:  MSH2, MLH1, MSH6, PMS2, EPCAM Cowden Syndrome (PTEN hamartoma tumour syndrome): Related cancers: Breast, thyroid, endometrial (uterine lining), and others. Genes:   PTEN. Familial adenomatous polyposis: Related cancers: 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. Gene: APC Retinoblastoma: Related cancers:  Eye cancer (cancer of the retina), pinealoma (pineal gland tumor), osteosarcoma (bone), melanoma, and soft tissue sarcoma. Gene: RB1 Multiple endocrine neoplasia type 1 (Wermer syndrome): Related cancers: Pancreatic endocrine tumors and (usually benign) parathyroid and pituitary gland tumors. Gene: MEN1 Multiple endocrine neoplasia Type 2: Related cancers: Medullary thyroid cancer and pheochromocytoma (benign adrenal gland tumor). Gene: RET Von Hippel-Lindau syndrome: Related cancers: Kidney cancer and multiple non-cancerous tumors, including pheochromocytoma Gene: VHL  

The Jolie Effect

There has been a substantial increase in the demand for genetic counselling and gene analysis (genetic testing) as a direct result of media exposure, resulting in the “Jolie effect”. You may well be aware of the film actress Angelina Jolie-Pitt. Angelina, according to the New York Times, disclosed her family history of breast and ovarian cancer and that she carried a mutation in the BRCA1 gene, which gave her an estimated 87 percent risk of breast cancer and a 50 percent risk of ovarian cancer. She had already lost her mother, grandmother and aunt to cancer. In 2013 she underwent a preventative surgical double mastectomy, and in March 2015 she decided upon further preventative surgery to remove her ovaries and fallopian tubes as well. Angelina’s story has definitely inspired many women who share a similar family history, to get genetic testing, and for Angelina it was clear to her to take whatever measures were available to prevent the cancer from developing in her. However for some women, the decision to go ahead with radical preventative surgery won’t be so clear-cut.  

Reducing the Risks of cancer in people with the BRCA1 and BRCA2 gene mutations

There has been a growing interest in risk-reducing, anti-estrogen medications such as tamoxifen in BRCA1 and BRCA2 carriers, who have not yet developed breast cancer. Whilst the evidence for effectiveness with these drugs is often reasonably good in certain circumstances, it is not for everyone. There are numerous side-effects to take into consideration such as hot flashes, vaginal dryness, increased risk of developing endometrial (uterine lining) cancer, increased risk of blood clots in the legs, lungs and brain, and increased risk of cataracts, including a 1 in 500 risk of death. Each individual case would need to be considered carefully. There are other ways to reduce the production of harmful estrogens in your body such as improving liver function and keeping your weight in the healthy range.   In our following article, Part 3, we will show you how you can further reduce your cancer risk by assisting the body to “switch off” the expression of any affected genes.   References: The National Cancer Institute The American Cancer Society The New York Times Adjuvant Online – Tamoxifen Side Effects   These statements have not been evaluated by the FDA and are not intended to diagnose, treat or cure any diseases.