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The Gene Scene

Have you ever wondered the likelihood of your children inheriting familial disorders? Or, the chances you may be affected with a malady passed on through your genes? With advances in genetic testing, you can find out.

Every Saturday morning, when I was about 10 years old, I watched the X-Men cartoons on TV. For 30 minutes a day I was lost in a world of superheroes and superpowers, powers like Professor Xavier’s telepathic abilities, Storm’s weather manipulation, or my favorite – Wolverine’s retractable claws, animal keen senses and healing powers. As an adult, when the movies were released one by one, I had a better understanding as to the source of their power: genetic mutation. These “mu- tants” possessed a genetic trait that elevated their human status into something supernatural. It was awesome. But in the world we live in, the notion that a mutated gene could produce super strength, flight or any other hundreds of powers couldn’t be fur- ther from the truth. In fact, a mutated gene can lead to thou- sands of life-threatening ailments, such as cancer, Huntington’s disease, cystic fibrosis and Tay-Sachs. So while X-Men’s theory on genealogy is fascinating, this is a story about real genetic mu- tations, the genetic testing to determine these mutations, and the real-life superheroes that have to live with them every day.  

“Your genetics are inherited from your mother and father to create the [chromosomal] spiral. So if your father has a gene mutation and you inherit that gene, then you have a 50/50 chance of passing that gene on as well,” says Carolyn Shore, breast health navigator and oncology nurse at Robert and Carol Weissman Cancer Center in Stuart.

So what does that all mean? Imagine you’re reading a book and on the page you notice a word spelled incorrectly. The word is no longer serving its proper function; it’s simply a combina- tion of letters whose meaning is reduced to nonsensical drivel. Now imagine a gene in your body is also read like a book. The misspelled word on a piece of your gene is a mutation, and ac- cording to Shore, that mutated gene can potentially lead to a slew of genetic disorders.

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This was definitely the case with Jupiter-based detective Lindsey Canonico. Canonico has inherited not one, but two ge- netic mutations. But in reality Canonico’s mutations pose a seri- ous threat to her health.

Cancer has been an unwelcomed visi- tor in her family for years. With villainous force, the disease attacked her aunt with breast cancer in 2011, her mother with ovarian cancer in 2008, and her grand- mother with breast cancer as well. Her grandmother, however, lost her battle to the disease, dying in her 40s. Certain she would be next on cancer’s list, Canonico knew she needed to do something. 

According to nurse Shore, 5 to 10 percent of breast cancers are a result of genetic mutations. “They’ll do a three- generation pedigree. If the mother, aunt and grandmother, for example, all have developed cancer, then there is obviously a familial component there,” says Shore of determining the candidacy of a patient’s need for genetic testing. 

Genetic testing can identify if indi- vidual genes or short segments of DNA have been mutated or changed, it can detect if there’s anything missing or added to the chromosomal structure, and it can look for some protein or enzyme activity through biochemical tests. 

Since Canonico’s family was knee- deep in cancer, genetic testing was certain- ly a route she felt was necessary to take. In May 2011, Canonico walked into her doctor’s office and had her blood drawn. She was being tested for the BRCA1 and BRCA2 gene mutations – harmful muta- tions in the BRCA1 and BRCA2 tumor suppressor genes known to cause heredi- tary ovarian and breast cancer. When her physician told her she tested negative for the mutations, she was immediately shocked. “I always assumed I was geneti- cally screwed,” Canonico, 32, says. 

On a single-page document marked “confidential,” Canonico’s BRCA1 and 2 results were revealed. Beneath three ad- jacent boxes, where her name, her physician’s name and a couple of different dates of when her blood was drawn and accessed were all listed, were the words, “positive deleterious mutation.” 

“Now, I’m not stupid, but I didn’t know what ‘deleterious’ meant. … I just knew something wasn’t right.” 

So channeling her inquisitive nature, the detective called Myriad Genetics, the laboratory where BRCA1 and BRCA2 mutations are tested, and began to dig a little deeper, despite what her doctor had said. They confirmed what she sus- pected all along – she was positive for the BRCA2 gene mutation. 

The genetic test Canonico under- went is not a soothsayer and therefore does not predict the future. It’s a screen- ing that first identifies the mutated gene and secondly reveals the patient’s likeli- hood of developing the disease. For Ca- nonico, the results disclosed she had an 84 percent chance of developing breast cancer and a 27 percent chance of devel- oping ovarian cancer. 

Not wanting to fall prey to cancer’s merciless wrath, Canonico elected to have a prophylactic double mastectomy, the removal of both her breasts to reduce the risk of developing breast cancer, and enhanced surveillance to monitor her risk of ovarian cancer. After surgery, that 84 percent chance of developing cancer plummeted to about 3 percent. 

“I stIll dIdn’t completely comprehend what  was goIng to happen If I tested posItIve. …  whatever those results are you know It’s goIng to change the path of your lIfe.” – AMY SHAINMAN

 

Canonico’s story doesn’t end there. Shortly after her mastectomy and her breast reconstructive surgery, she started feeling pain in the left side of her chest and had trouble breathing. She thought it was a complication from her surgery, so she went into the emergency room. It turned out that her blood was clotting more than normal, causing a pulmonary embolism. 

While on blood thinners for six months, she felt that there was something else wrong. So her hematologist suggested she take a genetic test for the Factor V Leiden disorder, an inherited disorder of blood clotting. That too came back posi- tive, and it was then Canonico was intro- duced to her second mutation. 

“I did and sometimes do still cry,” Ca- nonico says. “But I try to laugh at things because that’s all you can do.” 

“She [Canonico] is tough as nails,” says Dr. John Rimmer, Canonico’s breast surgeon in Jupiter. 

As a general surgeon and breast sur- geon, Rimmer’s practice is becoming more and more interested in genetic mutations – something he credits to Kristin Hoke. 

Hoke was an anchorwoman at Palm Beach County’s WPBF-TV 25 and was one of Dr. Rimmer’s patients. After being diag- nosed with breast cancer and undergoing chemotherapy, Hoke tested for the BRCA mutation; it came back as positive. While in remission her cancer came back, spread to her brain, and she died at 42 years old. 

“About 80 percent of cancers are es- trogen receptor positive. There’s this type of cancer called triple negative cancer, and they are particularly aggressive. Those cancers often spread to the brain early, and they’re the cancers BRCA patients of- ten get,” says Rimmer of the cancer that spread throughout Hoke. 

“The best chance to cure somebody is to treat them the way Amy [Shainman] got treated: prevention,” Rimmer says, refer- ring to the surgical route taken by another of his patients, Amy Shainman. 

Shainman, along with Canonico, is known as a “previvor” – someone who has a predisposition to cancer, but hasn’t been diagnosed with the disease. As the wife of Jon Shainman, a reporter for WPBF-TV 25, Shainman was friends with Hoke. She witnessed Hoke’s uphill battle and saw how the disease took her friend’s life. 

Shainman’s life was saved in Decem- ber 2009. That’s when she says Hoke and Shainman’s sister, Jan, who was diagnosed with ovarian cancer in 2008, encour- aged her to undergo genetic testing. “I still didn’t completely comprehend what was going to happen if I tested positive. … Whatever those results are you know it’s going to change the path of your life,” Shainman, 43, says. Also influential to 
her undergoing testing was Facing Our Risk of Cancer Empowered, or FORCE, a non-profit group devoted to improving the lives of people and families affected by hereditary breast and ovarian cancer. 

Shainman tested positive for the BRCA1 gene mutation; a mutation she in- herited from her dad and one of the three founder mutations associated with people of Ashkenazi Jewish descent. 

She was then recommended to Dr. Elisabeth McKeen, an oncologist at the Palm Beach Cancer Institute. “I remember that first appointment and feeling like Jon and I had been run over by a truck,” says Shainman, drowning in her emotions. 

But wanting to be one step ahead of cancer, Shainman gathered her composure and opted to have a hysterectomy, the re- moval of her ovaries, in March 2010, and a nipple-sparing and skin-sparing prophy- lactic mastectomy with reconstruction in September 2010 by Rimmer and plastic surgeon Dr. David Lickstein. 

Shainman has the courage of any heroine worth watching. She proudly lifts her shirt and reveals her new breasts that look completely natural. There are two faint scars on the outside of each breast of where the incisions were made, but aside from those barely noticeable imper- fections, her breasts are indeed perfect. “I feel my breasts look better than they did before,” says Shainman, who cut out  pictures of women’s breasts she wanted hers to resemble. 

The nipple and skin sparing proce- dures Rimmer conducts are sophisticated. It’s very important he protects the blood vessels that keep the skin alive, so that the skin, areolas and nipples stay intact. He goes all the way around the breast and takes everything out through a small inci- sion on the side of each breast. 

It’s been four years since Shainman’s surgeries, and she’s now the Palm Beach County outreach coordinator for FORCE, where she spreads awareness by organiz- ing outreach meetings and fundraisers. And by the fall of 2013 during the Nation- al Hereditary Breast and Ovarian Cancer Week and National Previvor Day, she’ll release her book, Resurrection Lilly – A Hereditary Cancer Memoir – Honoring the Past, Healing in the Present, and Hop- ing for the Future. She named it after her grandmother, Lillian, who died in 1934 at 33 years old from breast cancer. 

The hardest thing for Shainman af- ter her hysterectomy was the menopausal weight gain, but if that’s her biggest ob- stacle, she’ll take it. “If I’m able to make my kids breakfast, oh my goodness, I’m a lucky woman,” she says.

Even though the hysterectomy was a “no-brainer” for Shainman, she was a bit disillusioned because a part of her wanted a third child. But at the time she wasn’t aware of the pre-implantation genetic screenings available – a field Dr. Moshe Peress knows all too well. 

Peress’ techniques are by far some- thing straight out of Marvel Comics. As a fertilization specialist and the medical director of Boca Fertility, he is helping genetically mutated people – people who are looking to conceive a baby devoid of genetic disease. 

Peress has the ability to offer parents genetically normal embryo implantation through in vitro fertilization by eliminat- ing potential risks from expressing them- selves in their children later on in life. With the use of pre-implantation genetic screenings, Peress is able to identify single- gene defects and chromosomal abnormali- ties so that the implantation of healthy embryos is dramatically improved. 

So for example, if a husband and wife are each carriers of cystic fibrosis, a single-gene defect, and they want to make sure their unborn child is free of the dis- ease they seek Peress’ expertise. Peress can generate a bunch of embryos and test the embryos for the presence or absence of that genetic mutation. “So typically what would happen is that you may have a segment of the gene itself. We know the mutation, we know where the mutation is located, we know what causes cystic fibro- sis, so we create a DNA probe, which is basically that short segment of the DNA that is causing the disease itself,” says Per- ess, who did his reproductive fellowship at the Medical University of South Carolina. 

By creating the probe, Peress can test to see if the affected embryo has the same condition by paring the probe with DNA of the embryo. He can then find out which embryos have the single-gene defect and those that do are obviously not fit for im- plantation. 

So while pre-implantation genetic screening can detect single-gene defects, it can also detect certain chromosomal ab- normalities that include X- and Y-linked genes, such as Fragile X, Trisomy 18, Tri- somy 21 and Turner syndrome. And with the use of new technology, Peress can look at the chromosomal structure – by taking a biopsy of the placenta without hurting the embryo – to detect any extra or miss- ing chromosome. 

This is huge. A chromosomal analysis will prove whether or not there is an ab- normality in the embryo prior to implantation. Most women have to wait for an amniocentesis to get this level of accuracy, at which point they can put themselves or the baby in danger. And if the results come back positive for a mutation, they are then faced with having to make a moral deci- sion nobody should have to make: to keep or not to keep the baby. 

There is, however, a huge downside: cost. On average the IVF with pre-implan- tation genetic screening is $20,000. 

So what do you do if you have a genetic mutation and you’re looking to conceive, but you don’t have the money? That’s the million-dollar question, and it varies case by case. You may choose to adopt, to abstain from having children, or roll the dice and cross your fingers your child does not inherit your cursed gene. 

The good news is genetic research is a rapidly evolving area of study. Genetics is truly a whirlwind of information and according to Thomas Kodadek, profes- sor of chemistry at The Scripps Research Institute in Jupiter, gene research is only going to continue to blow blinds. On the topic of gene therapy he says, “There have been a couple of breakthroughs in the last couple of years with inventing technolo- gies to make gene repairs. Right now that’s absolute cutting-edge stuff that’s going on in few laboratories around the world. It’s been done in human cells, but it’s never been done in a person. It’s wildly exciting.” 

But until then, genetic testing will have to suffice. It has, after all, helped women like Jessica Tyson take preventa- tive measures and fight against the evil that is cancer.

Tyson lost her mother to breast can- cer when Tyson was 7 years old, and her grandmother was a breast cancer survivor. She says she always knew she would get cancer; she was just waiting around for the disease to strike. That is until one day she saw Shainman’s story on the news and felt compelled to speak to a genetic counselor. 

Around the same time her sister, Stacy, also underwent testing, but her tests came back negative. Or so she was told. Tyson took Stacy’s results with her to show the genetic counselor Tyson was meeting. The counselor’s jaw dropped when she saw it; she knew right away Stacy was actually positive for the mutation and had been told the wrong results. Within a week’s time, Tyson proved to be positive as well. “I knew in my heart it was going to be positive, but there was that hope that I wouldn’t be,” Tyson, 33, says. 

Tyson met with Rimmer and elected to have a prophylactic mastectomy. She didn’t want to live her life “six months at time” with advance screenings. 

Unlike Canonico, Shainman and Ty- son, Fort Pierce resident Linda Crist also underwent genetic testing, but she did it after she was diagnosed with breast can- cer in 2008. She was completely unaware of the test, but at the behest of Dr. James Vopal, a general surgeon specializing in breast surgery, she took the test. Her re- sults came back as positive for the BRCA2 gene mutation, so she had a hysterectomy and a mastectomy. “It really wasn’t a dif- ficult decision to get the mastectomy. I lost my parents young, so I chose to be proac- tive versus reactive,” Crist, 50, says of los- ing her mother to ovarian cancer and her father to colon cancer. 

Even though Canonico, Shainman, Tyson and Crist all elected for surgery, those are not the only options patients have after testing positive for a cancer mutation. There is either enhanced sur- veillance, which is just a fancier way of saying increased doctor visits for testing and ultrasounds, medicine to treat certain cancers, and, of course, surgery. 

According to McKeen, about 10 to 15 percent of cancers are ge- netically based. McKeen says the physicians at the Palm Beach Can- cer Institute pay close attention to patients who have cancer occurring in younger members of their fam- ily or if any cancer has been pres- ent in either the breast or the colon area. That’s why it’s imperative to  know your family history; it can save your life. 

The BRCA1 and BRCA2 gene mutations have received a lot of me- dia attention, but there are also gene mutations for colon, pancreatic, pros- tate and thyroid cancers. And let’s not forget Lynch syndrome – a type of inherited cancer of the digestive tract, particularly in the colon and rectum. People with Lynch syndrome have an increased risk of cancers of the stom- ach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, skin and prostate. Women with this disorder also have a high risk of cancer of the endometrium and ovaries. “You have to have three family members that have one of these related cancers that are also related to each other, and one of them has to be less than 50,” McKeen says about testing for Lynch syndrome.

McKeen further adds that if the patients are followed closely, then diag- noses can often happen at an early stage. “So the reason to do the genetic testing is to try to find what’s causing the cancer in the family – that’s number one. If they test positive that they have a mutation in the gene and we know the cause, then you can test other family members as well.” 

Anyone who has cancer or any other disease running rampant in their family should without a doubt consider genetic testing, but more importantly, should they decide to do so, they should speak to a board-certified genetic counselor like Con- stance “Conni” Murphy. The last thing anyone would want to have happen is what happened to Canonico or Tyson’s sister Stacy – being given the wrong results.

As the program coordinator for the cancer risk assessment and genetics pro- gram for Jupiter Medical Center, Murphy performs risk assessments for anyone who walks into the center for mammography or biopsies services. Everyone fills out a touch- pad that helps Murphy understand their personal and family risk of malignancies. She then sends them home with a packet of “about eight pages of homework.” The packet is filled with the most detailed of questions imaginable. A woman, for in- stance, would be asked how many children she’s had, if she breastfed, how many breast biopsies she’s had, if she’s menopausal, if the menopause was natural or surgical, the list goes on and on. Then it gets into fam- ily-related questions, for example whether the family member, living or deceased, was affected by any known malignancies. When she gets the packet back she draws out a formal family pedigree and then uses sever- al risk models designed to give the patient the empirical risk of cancer. 

“It’s a complete family history; every- thing about them matters,” says Murphy, who was recently one of more than 300 people worldwide to be invited to the only medical center that does an intensive ge- netics course in the world, City of Hope in Duarte, Calif. 

Murphy as well as other genetic coun- selors are experts in their field and they have Master of Science degrees in genetic counseling. In the United States counsel- ors are certified by the American Board of Genetic Counseling. They are not only equipped with the necessary tools to in- terpret the results, but they can equip the patient with the knowledge they need in order to make the appropriate decisions that best suits them – whether that be a negative or positive test result. 

Murphy, who is also a nurse prac- titioner, is constantly staying abreast of new research. For instance, she says there are two other syndromes that involve an increase of breast can- cer, which are also genetic mutations: Cowden and Li-Fraumeni. According to Murphy, the guideline now states that any woman who is 35 years old or younger who is BRCA negative and has breast cancer should be tested for Li- Fraumeni syndrome. 

There are some disadvantages to genetic testing. According to Dr. Su- san Poncy, director of All Women’s Healthcare of Jupiter, if insurance does not cover the test, it can cost a pretty penny. The BRCA1 and 2 test is $3,340, the Ashkenazi genetic test is $575, and a specific cancer test can cost $475, and that’s to name a few. However, if a patient does have a strong familial component of a genetic mutation, the general consensus among the physi- cians is that insurances will cover most of the expense. She also says it can take an emotional toll on a patient as well, but that’s where a genetic coun- selor can prove to be very helpful. They walk the journey with the patient and can be the pillar of strength needed in a  medical expert. 

Genetic testing is truly amazing. It’s a recognized field that has taken leaps and bounds in research. Keep in mind, genetic testing is still in its infancy stage with researchers discovering more and more about it every day. It’s continuously evolving, and there’s more to unearth. So while it can’t predict the future or uncover supernatural abilities, it’s a good tool to understand your susceptibility to disease, and from there you can decide how to proceed with your quality of life. So that more women like Canonico, Shainman, Tyson and Crist may be spared of their disease and live to tell their tale of hero- ism to someone else.