Sarah Miranda had no reason to believe in the life-altering possibilities of genetic testing, until results turned up a mutation connected to a rare form of stomach cancer.
When Jefferson partnered with the genetic testing company Color Genomics in the fall of 2018, it also committed to providing its 30,000 employees with free genetic tests. Through Color Genomics testing, employees would have access to their genetic information, including their hereditary risk for medical conditions such as cancer and heart disease.
It also quite possibly saved Sarah Miranda’s life.
Sarah, a nurse practitioner specializing in pulmonary vascular disease, was quarantined at home with her family last winter when she came across an email from Color Genomics, inviting her to claim a free genetic testing kit as part of the partnership with Jefferson. What the heck, she recalls thinking at the time, it’s free so why not give it a try? “I got the kit, spit into a tube and mailed it out. I really didn’t think much of it,” Sarah says.
It wasn’t long before she received another message from Color, explaining that the findings in her genetic test had detected an issue and that she needed to meet with a genetic counselor. “I didn’t take it seriously at all, but I went ahead and met with this person on Zoom and they tell me that I have this gene mutation that puts me at a high risk for stomach and breast cancer.”
Her thoughts immediately turned to her late grandmother, who passed away not long after being diagnosed with late-stage stomach cancer in 1996. Sarah was eventually diagnosed with a mutation in the CDH1 gene, which gives a person an increased risk of developing gastric cancer and other cancers associated with hereditary diffuse gastric cancer (HDGC). The mutation wasn’t discovered until 1998 – two years after her grandmother died. “My family thought she just had regular common gastric cancer,” Sarah notes.
During the height of the COVID-19 pandemic, Sarah traveled to the National Institutes of Health (NIH) in Maryland, where she underwent gastric mapping, during which some 88 biopsies were taken from her stomach. “They have a high-power microscope and they look for cancer cells and they look for progression of disease,” Sarah, 41, says. “And so they did find cancer cells – signet ring cell carcinoma. So I had to make a decision.”
According to the American Society of Clinical Oncology, individuals with a germline CDH1 mutation should consider having their stomach surgically removed, also known as prophylactic total gastrectomy, even if their endoscopy is normal. This type of surgery, ASCO says, is the only proven effective way to prevent diffuse gastric cancer in individuals with HDGC. People who decide not to have surgery to remove the stomach may consider an intensive surveillance schedule with their doctor, with an annual upper endoscopy exam with multiple (more than 30) mucosal biopsies. Previous studies, however, have shown that screening endoscopy exams often miss early-stage diffuse gastric cancers.
After discussing the options with her family, Sarah initially decided it would be best to have the total gastrectomy.
“This type of cancer, it’s not like a lump that’s visible to the naked eye if you were to put a scope down there and look,” Sarah explains. Diffuse gastric cancer is a specific type of stomach cancer, sometimes also called “signet ring cell gastric cancer” or “linitis plastic.”
The word “diffuse” is used because this cancer tends to affect much of the stomach, rather than staying in one area of the stomach. Approximately 20% of all stomach cancers are diffuse gastric cancers, and a small number of these are due to HDGC. The average age for someone with HDGC to be diagnosed with stomach cancer is 38, although it can be diagnosed much earlier or later than that.
“I was doing surveillance for about a year-and-a-half,” Sarah says, “and every six months I would get the test and they would find more cancer cells, but they’re all stage 1 cancer cells. So the recommendation was always total gastrectomy with the hope that I have a better recovery and a better outcome instead of taking the chance.”
But after an end-of-summer vacation with her family in September, Sarah had a change of heart. She decided to cancel her surgery and resume surveillance every six months. “My decision came about when I read an article about CRISPR and it gave me hope that change may come in my lifetime,” Sarah says. “My doctor is in support of my decision and my family is elated.”
CRISPR is short for “clustered regularly interspaced short palindromic repeats.” The term makes reference to a series of repetitive patterns found in the DNA of bacteria that form the basis of a primitive immune system, defending them from viral invaders by cutting their DNA.
Using this natural process as a basis, scientists developed a gene-editing technology called CRISPR-Cas9 that can cut a specific DNA sequence by simply providing it with an RNA template of the target sequence. This allows to then add, delete or replace elements within the target DNA sequence.
Cancer heads a list of some of the first diseases that scientists are tackling using CRISPR-Cas technology, testing its possibilities and limits as a medical tool.
The specific number of families with HDGC is unknown. The overall incidence of gastric cancer varies in different parts of the world. In the U.S., it is estimated that less than 1% of the population will develop stomach cancer of any kind; only a small fraction of these will be due to HDGC.
I’m definitely grateful for doing the tests and finding out and I do think it’s saving my life. I’m grateful to know that I don’t have any kind of other genetic problems and to know that this is something that is treatable if it’s done early enough.
Since Miranda’s diagnosis, several family members, including her sister, have discovered that they have the same CDH1 gene mutation. As for her immediate family, her son, 17, doesn’t want to be genetically tested until he’s in his late twenties and her daughter, 15, understands the implications of genetic testing and just hopes she doesn’t have the same mutation. “I’m hoping it just stops with me and doesn’t carry on to my children,” says Sarah.
She’s thankful that she went through with the genetic testing and hopes others learn from her experience. “It’s a blessing and a burden,” she says. “Once you know you have a genetic mutation and it’s a life or death kind of thing, it’s really burdensome to know. It’s much easier to be in denial and know that we’re all going to die eventually and when it happens, it happens. It is something that should be well thought out before doing genetic testing, because once you know, you can’t take it back.”
For now, Sarah, who grew up near Seattle, WA, continues her work as a nurse practitioner at Jefferson Health. She’s helping others – patients with heart failure, pulmonary hypertension, cardiomyopathy – and that’s helping her as she continues to monitor her cancer.
“I’m a worker, I’m a doer,” she says, “and I look forward to putting this behind me so I can get back to regular life.”
(Top photo credit: ©Kevin Monko)