LAWRENCE INGRASSIA can hardly remember a time when cancer wasn’t a reality for his family. His mother was sick through much of his childhood and died of breast cancer at 42, when Ingrassia was 15 years old. Both his sisters died of cancer: Angela from abdominal cancer in 1981 at 24, and Gina from lung cancer in 1987 at 32. His older brother, Paul, developed lung cancer, followed by colon, prostate and pancreatic cancers. Paul’s son Charlie had soft tissue cancer as a child and then colorectal and bone cancers in adulthood.
In 2014, Paul underwent genetic testing that revealed the cause of his cancer predisposition. The test showed a mutation in the TP53 gene, which causes a hereditary disorder known as Li-Fraumeni syndrome that results in numerous cancers, often at young ages, in the same family. Charlie died from bone cancer in 2019 at 39, and Paul died from pancreatic cancer later that year at 69.
As the COVID-19 pandemic began the following year, Ingrassia, who had retired from a career writing for newspapers like the Wall Street Journal and the New York Times, found himself looking for a new project. He decided to use his journalistic skills to learn more about the condition that had taken his nephew and all his siblings. He interviewed Joseph Fraumeni Jr., one of the researchers who in 1969 first published research suggesting a genetic link could cause different cancers in the same family. He met with families like his who were similarly affected and reviewed their medical records.
Three years of research culminated in the book A Fatal Inheritance: How a Family Misfortune Revealed a Deadly Medical Mystery, published May 2024. Part scientific history and part memoir, A Fatal Inheritance tells the tale of Li-Fraumeni syndrome by interweaving the narrative of how researchers identified the mutation with stories of impacted families, including the Ingrassia clan. “This particular book was not a book that I ever intended to write, but once I started to research, I realized that I was always meant to write it,” says Ingrassia, who did not inherit the mutation himself.
Ingrassia writes about cancer researchers Fraumeni and Frederick Pei Li, who, in the 1960s, heard a story about multiple people in a single family all developing different cancers, typically early in life. Despite the prevailing notion at the time that heredity had nothing to do with cancer, the two believed there had to be a genetic explanation, especially as they came across other similar families. The book follows the painstaking work of many scientists as they kept tabs on these families and analyzed their tissue samples, all leading to the 1990 study that showed a genetic mutation causes the cancer predisposition. Even with this knowledge, few options exist to prevent disease in people who have the mutation.
Because of his personal connection to the subject matter, Ingrassia found himself wearing two hats as he wrote the book: a journalist researching Li-Fraumeni syndrome, and a grieving son, brother and uncle diving into his family’s past. His research dug up emotional memories, like when he read the diary entries his sister Gina wrote about her feelings of anguish in the months before her death. “You’re coming across lump-in-throat moments where you catch yourself,” Ingrassia says. “It was cathartic at times, but it was really moving at times.”
Ingrassia spoke with Cancer Today about what the history behind Li-Fraumeni syndrome can teach readers about scientific discovery and how he hopes sharing his family’s story can empower others with hereditary cancers.
CT: Why do you think more therapies for hereditary cancers have not been developed yet?
INGRASSIA: Cancer is just such a complicated disease. Treatments have improved for cancers in general; the outcomes for some types of cancers are dramatically better, in part because we’re detecting the cancers earlier but also because of very targeted treatments that go right to the cancer cells and kill them.
When you get to hereditary cancers, that’s where it gets especially tricky. I just think that cell biology and figuring out how to reverse dangerous mutations has proven to be much more perplexing, much more difficult than scientists originally thought.
But it’s hard to tell families who are dealing with this, “You have to look at the progress that has been made over time.” That’s not any assurance.
CT: What was your motivation to write this book?
INGRASSIA: There are essentially two stories here. There is this heartbreaking story of my family and these other families dealing with all these painful cancers and deaths, but also there is this inspiring story of the dedicated researchers who, despite lots of obstacles, refused to give up. They kept pursuing this mystery until they solved it. My goal was to honor my family and these memories, but I also wanted to give recognition to the scientists and, ideally, if other researchers read the book, inspire them.
When I gave a speech at the National Cancer Institute, I said, “What I do is similar, in a way, to what you do; I’m looking for answers. But I’m writing a book. You’re trying to save lives.” A few doctors came up to me afterward, and they said, “What you do actually is important because you are telling people how we work and how difficult scientific progress is.”
Maybe writing about what these doctors helped accomplish is going to inspire future researchers to find the drug that will work or to explain some other disease that currently is puzzling.
CT: Was it difficult for you to write about painful family memories?
INGRASSIA: In one way, it was hard, but in another way, I really felt this obligation to them. I felt it was a way of honoring them, preserving their memories and saying, “You will not be forgotten.”
A lot of this book is about lives cut short. My sisters died at 24 and 32, my mother at 42, then my nephew at 39. Many of these families have had children and young adults die. I wanted to tell readers, “Look at what these people missed out on that the rest of us all take for granted as part of our everyday life. We’re going to have a lot of experiences, and there could be ups and downs in life, but because of these genetic mutations, a lot of people aren’t going to get that.”
CT: How have people responded to the book?
INGRASSIA: A guy wrote me and said, “Your family is my family.” People have said, “There’s finally somebody who’s described what we are going through.” Li-Fraumeni syndrome is something that’s hard to explain to people and to get your head around—how you can get cancer at any age, any time, and different people are going to get different cancers at different times. I think it’s just hard to try to explain this stuff to people, and now they feel that somebody has actually told our story and told the story of Drs. Li and Fraumeni.
CT: What do you hope readers take away from the book?
INGRASSIA: One thing is—especially for families with Li-Fraumeni syndrome but also for people with other types of hereditary cancers—you’re not alone. There are other families out there like you.
Moving forward is painful, and it is difficult, but it is also possible. Cancer was a constant element in our lives, but it didn’t become our lives. To the extent that you can, try to live your life and embrace your family. That’s a takeaway: It will always be a part of you, but don’t let it be you.
