23-05-2025
He lost his mother, sisters, and brother to cancer. It was in their genes.
Later in life, he understood it was no coincidence: threaded throughout his family's DNA was a hereditary cancer gene, vastly increasing their risk of the deadly disease. In this episode of 'The C-Word' series, 'Say More' host Shirley Leung talks to Ingrassia about the moment he discovered the cause, the difficult choice of getting himself tested, and how greater knowledge of family history can lead to monitoring that saves lives.
The following is a lightly edited transcript of the May 22 episode of the 'Say More' podcast.
Shirley Leung:
Welcome to 'Say More' from Boston Globe Opinion. I'm Shirley Leung. This is episode four of our five-part series 'The C-Word: Stories of Cancer.'
For years,
His mom died of cancer in her 40s, followed by his two sisters who also died young. And it didn't stop there.
Cancer kept popping up in the family, like a horrible game of whack-a-mole.
When he got older, he learned it was no coincidence. Threaded through his family tree was a deadly cancer gene.
Science on the genetic roots of cancer has come a long way, and a better understanding can help save lives.
Larry's recent book is called '
Larry Ingrassia:
I was very young when my mother had cancer. She died when I was 15. She was 42 years old. But my memory is that she had breast cancer for eight to 10 years. She survived it initially before she died.
My memory is a bit fuzzy, but I do remember these enduring memories of visiting her in the hospital with my three siblings. I'm the second of four with an older brother and two younger sisters. That was always hovering over us, that she was sick.
But then, she would be fine. Then it seemed like a couple years later something else would happen and she would go back.
It was in the spring of 1968, when I was 15 years old, she was in the hospital and I didn't think much about it because she'd been in and out of the hospital for any number of years.
I was a bus boy at a breakfast restaurant not far from our house in suburban Chicago. I was on a shift. It was kind of late in the morning and I remember my father came to the restaurant. One of the workers said, 'Your father's out back, he wants to see you.' And I was like, 'Oh my God. What's that about?'
I went out back and he said, 'Mom's dead.' And so I was really shocked. Even though she had been ill, I just didn't have any inkling.
Back then, in the 1960s, people didn't talk a lot about cancer, a lot about illness. So it was a real surprise.
A family portrait of Larry Ingrassia (third from left) and his siblings in the 1950s. Three would die of cancer.
Handout courtesy of Ingrassia family
Leung:
Your mom gets cancer and then your sisters. One of your sisters first, then another.
Ingrassia:
It was another decade before there was another cancer in our family, and my youngest sister, Angela, was 23, and she developed abdominal cancer. She died within about six months. She was 24.
And again, it was really a shock. About a year later, one of my brother's sons, Charlie, who was two years old, developed a soft tissue cancer in his cheek.
Now he survived. Again, it was a totally different kind of cancer. The prognosis was not good, but we were lucky he survived.
Another five years after that, in 1987, my sister, Gina, got lung cancer and died about six or seven months later. By that time, we were wondering, 'What is going on?' We weren't sure what was going on. Again, no oncologist said to us, 'Oh, we think that there is something hereditary going on.'
Leung:
You had theories, right?
Ingrassia:
Yes, and I think there were some reasons for this. Our father was a research chemist. We thought maybe he brought home chemicals, tiny particles on his clothing after work. He would pick up the kids when he got home, especially when we were young. We thought that maybe we would ingest it, our mom would ingest it, and then years later, you don't know how many years later because cancer can take very long to develop, it would manifest itself in cancers over different parts of the body.
And it's a plausible thing because there was this growing understanding of environmental carcinogens and particularly chemicals that could cause cancer. We were puzzling over all the cancers in our family. Doctors were puzzling over, not my family because we weren't studied, but similar families and they were also swimming against the tide because there was not a belief that heredity was a major factor in cancers.
And this is where my book begins. In the late 1960s, again my mother died in 1968, which was around the same time, two young doctors at the National Cancer Institute were examining causes of cancer. They were young, they weren't experts at the time. They were looking for interesting cases and they came across a very unusual case.
There was a father who was 23 years old and had leukemia, and shortly thereafter, his 10-month-old son developed a soft tissue cancer in his arm. Both of these are rare, especially at those ages. The combination and the odds are considered astronomical. So these doctors said, 'Wow, maybe we should study this family to find out what's going on.'
And indeed, when they started looking at that family, they found cancers going back generations.
They found many cancers throughout the family, and a lot of young cancers, as well. They found women in their twenties and thirties, but also children having cancers, too. They didn't know exactly what was going on, but they did write a paper published in 1969.
They raised the question of whether there was familial syndrome. This was a seminal paper that turned out to be very important. Interestingly, the paper was published and the experts in the field, who of course were mostly focusing their research on viruses, were highly skeptical.
They said, 'These cancers that you're talking about, they're all different kinds of cancers. What could they have to do with each other? How could that be hereditary if they're all different kinds of cancers?'
To their credit, these doctors, Frederick Li and Joseph Fraumeni, both children of immigrants, persisted. They said, 'Let's keep studying this family and other families.'
A 1991 photo of Frederick Li (l.) of Dana-Farber Cancer Institute and Joseph Fraumeni of the National Cancer Institute discovered how some cancers can be inherited in what is known as Li-Fraumeni Syndrome.
Handout from National Cancer Institute
Leung:
And that's what's known as Li-Fraumeni syndrome, right? And how did you learn that your family had Li-Fraumeni?
Ingrassia:
Okay, so my brother in 1997, when he was 46 years old, developed lung cancer. Again, he was given a low chance of survival.
He had a lung removed and he survived. We were again lucky. But then he had another cancer around 2005. He had prostate cancer. Finally, in 2014, one of his doctors said to him, 'Given all the cancers in your family, maybe you should undergo a genetic test, because I think that the history indicates that you may have
Leung:
This is p53, right?
Ingrassia:
P53 is the specific gene. The p53 cancer suppressor gene protects cancers from occurring anywhere in the body. It's actually called, since it was discovered, the
That's why people who have the inherited p53 mutation can get cancer anywhere in the body. It's not site specific. So the types of cancers are myriad.
There are a handful of major cancers in p53. One of them is breast cancer. Leukemia, soft tissue cancer, skin cancer, colon cancer, brain cancer are a huge variety of cancers that can be linked to the p53 mutation.
Leung:
Going back to 2014, when your brother Paul calls you and says, 'I have this gene. I think I have Li-Fraumeni syndrome.' Did knowing that he had that genetic mutation help with his treatment of his cancer?
Ingrassia:
Yeah. So, what do you do if you have this inherited mutation?
First of all, the inherited mutation, like any inherited mutation, cannot yet be fixed. But if you have the inherited mutation, you know that the odds of you getting cancer are very high. And, also that the odds are pretty high at a fairly young age.
So by age 40, if you have the inherited p53 mutation, 50 percent of people with the mutation have cancer. That's versus 5 percent in the overall population. It's 10 times as high.
Often, as I mentioned earlier, it's children. It's really sad. And in a lifetime, if you have the p53 mutation, it's like 95%.
So, some doctors who were involved in studying p53 said, 'Given that propensity, can we help people by giving them extensive, regular screening?'
The advantage of knowing if you have the inherited mutation is that you can get annual full body MRI scans. You can get blood tests, you can get all sorts of tests.
In my brother's case, I think it actually prolonged his life by a couple of years. After he had his testing, it was positive for the p53 mutation and he knew he had Li-Fraumeni syndrome, so he began regular scans. In 2017, the scan detected pancreatic cancer on the tip of the pancreas.
Usually you don't find pancreatic cancer until you have symptoms, and it's too late. Pancreatic cancer is one of the deadliest cancers. In his case, it was found early. They were actually able to do an operation and get rid of the tumor on the tip of his pancreas. However, two and a half years after he had that surgery and survived pancreatic cancer, it came back in his lung.
He died when he was 69, in 2019. Sadly, it was seven months after his son died of his third cancer.
Newsweek cover of the p53 gene that would lead to a better understanding of cancer.
Newsweek, 1996
Leung:
And Charlie was only how old?
Ingrassia:
Charlie was 39. This is where I would argue for people who say they don't wanna know because they don't wanna have it over them. 'I know I have this mutation. My children have the mutation. I'm gonna be worried all the time.'
Not knowing doesn't change whether you have it or not.
I say knowledge is power. And this is why I wish that we had learned earlier in 2010 when Charlie had a second cancer, colorectal cancer. He started having problems at the beginning of the year.
It wasn't until the summer that he was diagnosed. I think maybe his guard was down, he'd gone almost three decades after surviving his childhood with cancer. But it took quite some time before they finally said, 'Okay, let's do a colonoscopy.' And by then, he had a later stage of colorectal cancer.
Again, he survived amazingly, but he survived in part because they gave him heavy doses of radiation to kill the cancer cells. The problem is, if you have Li-Fraumeni syndrome and you have p53 that can't fight against potentially cancerous cells the way that it normally would, radiation can plant the seeds for future cancers.
Sure enough, in 2017, a month or two after my brother was diagnosed with pancreatic cancer, Charlie was diagnosed with his third, and final, cancer. It was bone cancer in his hip, right where he was getting all that radiation to kill the colorectal cancer.
The odds of him living a long life given the family history were probably not good. But I do think that it might have made a difference.
If he had known in 2010 and he'd been diagnosed right away, it wouldn't have changed whether he'd gotten the cancer, colorectal cancer or not. But the earlier diagnosis might've meant they would've had a lot less radiation to kill it. It might've meant that it wouldn't have come back in his hip.
And that was one of the really sad things. It was so hard to watch for this young man. They had to amputate his leg, including his hip, in a desperate attempt to save his life. But the cancer kept spreading after that. About six months later, not long before my brother died, Charlie died.
Leung:
That was the hardest part of your book.
Ingrassia:
It was. It was incredibly hard to go through and it was incredibly hard to watch and to write about and talk to his friends. But, I feel more connected to my family because of the research that I did. Obviously I knew a lot about my sisters and their cancers, but I learned more about it in this process.
My sister Gina began keeping a diary from the time that she learned that she had lung cancer until just before she died, six or seven months later. It was a combination of wonderful and painful to read about.
One of the most painful things, if you go back in the eighties, was that it was a time when there was a lot of belief in mind over matter.
If you just had the willpower, you could fight illnesses of all kinds.
Of course, the corollary to that is if you're not getting cured, it's your fault because you don't have the right amount of willpower.
I sensed that in reading her diary that she felt that it was on her and if she wasn't getting better, it was not her fault, but certainly that she contributed to it.
All I could think of is, 'No, you don't know that you have this mutated gene inside you that basically has doomed you.'
So, there were a lot of moments in writing it like that. My sister Angela, who was so young. I talked to a lot of her friends about her struggling with this and how difficult that was.
If you could just put yourself in her mind: you're 23 years old and you're the youngest of the siblings. She learned she has cancer, and we learned pretty early on that the outlook is not gonna be great because the doctor said, 'Well, I operated. I did what I could, but it spread throughout her abdomen.' It was about a six month period and it was pretty much downhill.
I wanted to talk to as many people who knew my sisters as I could. I wanted to talk to her oncologist and I wasn't sure of his name. My sister-in-law remembered a last name, so I started doing research. I'm a reporter and sure enough, there was a name that popped up.
It looked like he had recently retired. I sent a note, and if I might, I'll just read a little bit from the book about this.
(Excerpt from book):
My eyes welled up the instant I saw the subject line on the email that had just appeared in my inbox. 'I have never forgotten your sister.'
Only a few hours earlier, I had sent a LinkedIn message to a retired doctor wondering if by chance he happened to have treated my sister Angela, 40 years earlier. Was he Angela's doctor? And even if he was, what were the chances he might recall? One patient he treated many years earlier out of the thousands he had cared for.
'I realize you may not remember my sister Angela's case as this was decades ago' I wrote. 'But if you do, I'm hoping to speak with you.'
I wasn't sure if I'd even hear back, so his quick response floored me. 'The day after your sister died, I received a beautiful flowering plant at home. Not only do I remember her, so does my wife.'
I was in tears then and I am now.
I just think about my sister, 23 years old for a young woman. Her whole life was ahead of her. This is about a life loss, a stolen life.
There was a one word message that came with the flower to all of us: 'forward.' The fact that she was dying, but she wanted us to grasp life, it's pretty profound for a then 24-year-old. That was one of those many moments in writing the book. It stopped me.
Leung:
Larry, I don't know if you know, but one of the reasons why I'm so interested in cancer is
So my entire life I'm like, 'Will breast cancer come from me?' This question of 'Will I get cancer?'
My mom didn't get breast cancer, but I did. It was because of early detection, mammograms. I was detected early and so I'm cancer free. I had a mastectomy. I didn't have to go through chemo, so I'm one of the lucky ones.
I think reading this book, you're always wondering, 'Why did I get cancer? And why no one else?'
And for you, many other members of your family got cancer. That's why you wrote this book.
So do you feel like you are satisfied with the answer on why cancer struck your family so many times?
Ingrassia:
I'm heartbroken and sad that I lost all my family to cancer, especially so many so young. But my brother and I often talked about how blessed we were in many ways.
We were the children of poor Italian immigrants and we ended up doing things and achieving things that we never would've imagined growing up.
I always say that it's not really right to say 'Why me?' about all the bad stuff in your life if you weren't also asking 'why me' about all the good stuff.
I think I decided long ago to try to celebrate our good fortune in life and not dwell on or be angry. It's not a matter of being sad, of course I'm sad. I think often of my family and missing them and not being able to grow old with my siblings. But I try not to dwell on 'why me.'
It's part of genetics. There's no control over it.
Leung:
Now it took you a year to get tested. Why did you wait so long?
Ingrassia:
I don't know. I was busy, but what happened was my daughter began pestering me. 'I want you to get tested.'
It would be very rare, but it's possible to inherit the p53 mutation and not get cancer. There's that tiny 5 percent. Nobody knows why. There's still so much they don't know. They've learned a lot. They still don't know.
If I had the mutation, there would've been a 50% chance that I passed it on. So it was really because that's what I wanted to know, if I passed it on to my children.
It was only after I realized that, that I got tested. That's why she wanted me to get tested. But that was really the impetus for me. That was why I finally said, 'Okay, I'll do it.'
Also, quite frankly back then, getting a genetic test was quite expensive. It was $3,000 to $5,000. So I was lucky my brother, through his oncologist, found a study that was being done at the University of Southern California. I was living in Los Angeles, and I was able to get it in, do it without any cost.
Now you can get a genetic test for $250. Often if you have a history of cancer in your family, your insurance company will cover it. The cost is a lot lower. They have these multi-panel tests where they can find out if you have any number of cancer mutations. Some people have more than one.
Leung:
So in your book you mark the date July 10th, 2021. Tell me about the significance of that date.
Ingrassia:
When I was writing the book and researching the book, at some point you're thinking a lot about death and not necessarily in a sad way, sometimes in a sad way, but you're just thinking about life and death and the arc of life. At some point, I realized that the date was going to be the day that I would be one day older than my brother when he died, and that would make me the longest living member of my immediate family.
I said, 'You know what? I wanna do something that day.'
Celebrate is the wrong word, it's really commemorating that day. It's more of a memory of that day. So, I pondered a lot, 'Okay, what can I do that would be kind of a little bit interesting and a little bit fun? That says I'm glad to be alive. I'm lucky to be alive.'
I pondered a bunch of things, maybe go for a long hike and go paragliding. Finally I found a place in Los Angeles that had something that's called a
Leung:
I had to Google that. I didn't even know what that was.
Ingrassia:
I had never heard of a gyrocopter either. A gyrocopter is like a tiny helicopter, about the size of a big motorcycle. You can fit two people in. The great thing about it is that you actually kind of almost see even more than a plane. You have this bubble in front of you. You can see everything.
It was just like, 'Oh my God, I wanna do that.' So I told my wife.
I said, 'Vicki, I'm gonna take this gyrocopter.' And she said, and of course she didn't know what it was, 'Okay, so on the day that you become the longest living member of your family, you're gonna put your life at risk?'
And I said, 'You're right.' I thought it was a great line. I said, 'Yeah, but I'm gonna do that anyway.'
I just felt that I wanted to do something where I felt really alive. I could be in awe of this kind of human experience.
I got on that gyrocopter. It was about an hour. It's like this tiny thing that went up and down the California coast, which is pretty spectacular. I felt alive.
Let me see if I have it here in the book.
(Excerpt from book):
I felt an exhilarating rush of adrenaline and yes, one or two stomach churning ones, too, as the gyrocopter dipped and spinned. I contemplated what my mom and dad and my brother and sisters would've made of my jaunt. I'm pretty sure they would've rolled their eyes and then smiled happy that I was doing something just a little bit wacky on this day for them and for me, for us. Because they couldn't.
Regina and Angelo Ingrassia on their wedding day. Regina would pass on a hereditary cancer gene to three of four children. Regina died of breast cancer in her 40s. Three of her children got cancer as adults and died.
Handout courtesy of Ingrassia family
Leung:
You say this book is a love letter to your family. So what do you mean by that?
Ingrassia:
It's a love letter because, especially my sisters and Charlie, their lives were cut short and I wanted to make sure that these lives that were cut short were never forgotten even though they were short lives.
I think it's also a little bit of a love letter to other families like this. One of the things that's been most touching to me has been people who've reached out to me since I wrote this book, those who say 'thank you.'
It's so rare when somebody says they have Li-Fraumeni syndrome.
So for them to be able to say, 'You've given a little bit of a voice to us. You've helped us have an identity within this community,' I've been really touched by the number of people who have reached out to me.
And again, some of these letters…
Leung:
You got letters from people?
Ingrassia:
Yeah.
Leung:
Yeah, that's great.
Ingrassia:
Yes, most of these kinds of messages I would say I printed out. I cried this week when this book came out, not because I wrote it or had anything to do with it, however, because it is part my story, too.
I have Li-Fraumeni syndrome. I'm grateful for this book. Being a call for grace, hope, and continued investment in a fight against all cancers that steal those we love and that steal our own futures.
Another message was, 'I just finished 'A Fatal Inheritance.' I don't think I've ever sent an email to an author before, but I wanted to thank you for sharing your family's story. As someone with an inherited mutation that has unknowingly passed it along to two thirds of my kids, I'm always seeking to learn more about my mutation in the latest surveillance and research.'
Leung:
Did you expect that?
Ingrassia:
No. This is one of the things I think that was especially moving and especially touching about the book, to hear from total strangers saying the commonality was like, 'Your family is my family.'
Those were the moments in writing the book that touched me the most.
Leung:
Larry Ingrassia is a journalist who has worked with the Wall Street Journal and the New York Times and the Los Angeles Times.
His latest book is called 'A Fatal Inheritance: How a Family Misfortune Revealed A Deadly Medical Mystery.'
Listen to more 'Say More' episodes at
We want to hear how cancer has changed you. Email us at saymore@
If you like the show, please follow us and leave us a review.
Kara Mihm of the Globe staff contributed to this report.
Shirley Leung is a Business columnist. She can be reached at
