The Register Citizen (Torrington, CT)
Gene project may have saved woman’s life
WOODBRIDGE — It started when Joanne Barrett’s husband, Wynne, received an email in October 2020 inviting him to take part in the Generations Project.
He invited her to join him in the project, in which their genomes would be sequenced, and Joanne Barrett is convinced it saved her life.
“I said, sure, yeah, send me the information, and then I forgot all about it,” Joanne Barrett said. “So I didn’t actually get my blood sample until June of 2021. And so it was very random that I did this, because I don’t have any genetic reason for any of these things that the study looks at. I just did it for research.”
The Generations Project, launched by Dr. Michael Murray in 2019, is a long-term cooperative project between the Yale School of Medicine and Yale New Haven Hospital to sequence the genes of 100,000 people, in order to look for the genetic causes of diseases and other factors of human health.
So far, the project looks at 10 specific genes, as well as the material between genes, implicated in certain cancers, heart disease and stroke, and six more that can help doctors determine how to prescribe seven specific medications, a field known as pharcogenomics.
Over time, however, Murray said, more of the participants’ 20,000 genes will be studied, and they will be able to know whether they are susceptible to other diseases.
As it turned out, Barrett did have one genetic mutation: BRCA2, the one that comes with a higher risk of breast and ovarian cancer. As an extremely cautious person, she decided to have a double mastectomy, breast reconstruction and removal of her ovaries and fallopian tubes.
The surgeries were delayed because Barrett tested positive for COVID-19 in December, but she had them all done Feb. 16. On April 11, she also had her uterus removed.
She said she could have gone back to her job the next week as special education and transition coordinator for the Milford public schools, developing worksites in the community for special needs students, but it happened to be spring break.
“The belief is that my uterus is not impacted by this mutation,” she said. “It was peace of mind and just to reduce any possible potential stray cell from finding its way.”
While she didn’t have breast cancer, it turned out Barrett did have serous tubal intraepithelial carcinoma in her fallopian tubes, which “would have become a very aggressive ovarian cancer without me ever knowing until I was very sick with it,” Barrett said. “And so the beauty of this study is that it provided a person like me who has no family history an opportunity to get this information about my genetic makeup.”
When the pathology results came back for her fallopian tubes, her surgeon, Dr. Elena Ratner, said, “‘I don’t know if you believe in God, but you definitely have an angel.’ Because they did all sorts of tests before the surgeries,” Barrett said. “I’ve had MRIs, ultrasounds, multiple tests and nothing indicated any sign of cancer.”
Several other family members since have joined the study, which requires only a blood or saliva sample, and is free to join. Murray said Yale New Haven has committed to providing care for any participant who finds they need it, whether the person is insured or not. Her husband, sister, a brother and daughter are all negative for any issues, though she hasn’t heard from every family member.
“So I’m totally eternally indebted to, first of all, my husband for sharing this email,” Barrett said. “But secondly, really mostly, to this Generations Project because, had they not put that study together, I wouldn’t know until it’s almost too late.”
While Barrett immediately decided to have the surgeries once she knew of her cancer risk, she said, “I’m not going to lie. This has not been an easy road. I mean, it’s been physically very difficult, emotionally difficult, but when you consider the flip side, the risk factors are so, so high for cancer that it just makes sense.”
Barrett said she realizes that her decision was easier because she is post-menopausal, and that a woman in her 30s or 40s might make a different decision about whether to have surgery or to have mammograms and ultrasounds every six months.
Now, because it’s so easy to participate and so valuable, she wants to get the word out about the project as widely as possible. “I told Dr. Murray, I said, I’ll stand on a street. I’ll get out flyers. I’ll do everything you want me to do to help promote this,” because “if one other person can learn about a mutation like I have that there can be risk-reducing surgeries for, and then they ended up having their life saved like I did,” it’s worthwhile.
Murray said the long-term project hopes to collect samples from 100,000 people and now has 4,500 samples. They will be subject to whole exome sequencing, performed at the Yale Center for Genomic Analysis at the West Campus, and also to a snip array, which looks at the space between the genes.
“The part of the project that we’re emphasizing here is that once we have somebody’s genetic code, we can go back in and look at that, and look particularly for things that could be valuable to them and their health care provider that they probably don’t otherwise know about,” Murray said.
“Part of the idea behind the title Generations is that we think this will go on for generations, and it will bring value to individuals and families throughout generations,” he said. “So you know, hopefully, Joanne and folks like her will not only personally benefit but their families could get benefit also from knowing that this is running in the family and being tested for.”
Now, they are only looking at 10 of the 20,000 genes, “because those 10 we think have value and enough knowledge around them that we know what to look for, and we know how to use the information if we find something isn’t right in those 10 genes,” Murray said.
“So like Joanne, when she found out she had a change in that gene, I called her from the project and told her what we had found,” he said. “I told her what it meant, what it did mean. And then we got her in touch with the right experts within the health system to take the next steps with her.”
The 10 genes the project is studying are BRCA1 and BRCA2, four genes that can lead to Lynch syndrome, implicated in colon and endometrial cancer, three genes whose mutations cause familial hypercholesterolemia, which could increase risk of heart attack and stroke, and one related to cardiac amyloidosis, which leads to a buildup of protein in the heart, preventing it from pumping properly.
“So the basic operating principle is that
we only look for things that we can interpret, and you can do something with,” Murray said. “So we don’t look, for instance, for any genes related to things like Alzheimer’s disease, which there’s not any specific action that we could tell somebody to take if we found something there.”
Murray said anyone can participate. “We have had people all across Connecticut and across the region that have joined and there’s no limitation based on age or health status,” he said. “So we’ve got children that are participating. We’ve got people over 90 years old that are participating and everything in between. … I always only halfjokingly say, you have to be human and you have to be alive.”
People have to volunteer, however. The project will not reach out to family members of participants; that’s up to those taking part to spread the word, Murray said. He said if something is discovered in a person’s genome after he or she has died, the next of kin would be notified.
The collaboration between the School of Medicine and Yale New Haven Health is important so that any findings can be acted on, Murry said.
Yale New Haven “made the commitment at the start of this project that no one would fall through the gaps,” he said. “So, when I give somebody back a result that says they might be at risk for colon cancer, if they can’t go and get a colonoscopy, then I haven’t done them any favor. … So Yale New Haven Health System has agreed that those results will be followed up even if somebody’s in an insurance gap or whatever.”
Barrett said her care was covered by her health insurance.
For more information or to enroll in the project, call 203-605-6884 or email generationsproject@yale.edu.