July 10 was a bittersweet and emotional day for me this year, one I had marked on my calendar long before it arrived. It was the date, at 69 years and 30 days, that I became the longest living member of my family. I was then one day older than my brother when he died. My father died at age 59, my mother at 42, and my two younger sisters at 32 and 24. Except for my dad, all died of different types of cancer.
In the U.S., life expectancy is nearly 80 years. In my family, not including me, the average life span was 45.
It turns out there is a genetic mutation in our family that predisposes those who carry it to developing malignant tumors of all types. Statistically, there’s a 50-50 chance of inheriting the mutation, but in our family three of four siblings had it. I’m the only one who didn’t. Life and genetics are random that way.
For many years, we wondered if the tumors were related to my dad’s job as a research chemist in the wood products industry. Perhaps he had unwittingly carried toxic substances home on his clothes, and when he hugged us we had breathed in tiny particles that, over time, triggered cancers.
But that wasn’t the case. I’ll never forget getting a call from my brother, Paul, around 11:30 a.m. on Dec. 8, 2014, while at my desk at the New York Times. He told me he was taking a genetics test at the recommendation of his longtime oncologist due to his personal and family history of cancer. His doctors suspected he might have Li-Fraumeni syndrome, a rare condition named for the two doctors who had discovered it. When he got the lab tests back a few weeks later, there was no ignoring the stark words in capital letters at the top: “RESULT POSITIVE – CLINICALLY SIGNIFICANT MUTATION IDENTIFIED.”
Significant? True, but how about dangerous? Or life-threatening?
There are many genetic mutations linked to cancers, but the mutation inherited by Li-Fraumeni families is especially pernicious. It’s in the p53 gene, a cancer suppressor gene known as the “guardian of the genome” because it regulates DNA repair and cell division. p53 has the remarkable power to stop potentially cancerous cells — cells we all carry — from developing into tumors. That is, when it is working properly. When there’s a mutation in the gene and it doesn’t work properly, the consequences can be tragic.
Individuals born with the p53 mutation have a 90% chance of developing cancer in their lifetimes, a higher rate than with most mutations. Many experience their first tumor in early childhood or as teenagers, and develop multiple malignant tumors if they survive their initial cancer. Before my brother died, he had a half dozen or so cancers, including lung, prostate, and pancreatic cancer. My mom had breast cancer, my sister Angela had cancer in her abdomen, and my sister Gina had lung cancer, though a different type than my brother. One of his sons, Charlie, had his first cancer in his cheek at age 2, then had colon cancer when he was 30 and died of cancer at age 39 — seven months before his dad/my brother died — after having a leg and hip amputated in a futile effort to save him.
Most people haven’t heard of Li-Fraumeni syndrome because it is so rare. In fact, even we hadn’t heard of it until my brother got his genetics test.
After Paul died in 2019, I yearned to know more. So I did what I intended to be a quick internet search. What I discovered put me on an unplanned odyssey to understand Li-Fraumeni syndrome and my family’s cancers.
Physicians Frederick Li and Joseph Fraumeni Jr. were young epidemiologists at the National Cancer Institute in the 1960s who became intrigued about the causes of childhood cancers, which are uncommon. They soon stumbled across a handful of families with a staggering rate of seemingly unrelated tumors. In an article in Annals of Internal Medicine in 1969 — a year after my mother died — they hypothesized it might be a hereditary condition. But they weren’t certain, so they ended the title of their paper with a question mark: “Soft-Tissue Sarcomas, Breast Cancer and Other Neoplasms: A Familial Syndrome?” It was greeted with skepticism by the medical research establishment. The unusually high number of different types of cancer among members of the four families in the study must simply be chance, a statistical oddity, they were told. Or perhaps there was an unknown environmental cause. But it wasn’t heredity.
Li and Fraumeni persisted, and were eventually proven right. The discovery of the p53 mutation, more than two decades after their first paper was published, was such big news in the medical world that it was reported at the top of the front page of the New York Times on Nov. 30, 1990, under the headline “Researchers Find Genetic Defect That Plays Role in Some Cancers.”
I’m now working on a book about how these two pioneers — joined by other scientists over time — found the answer to this medical mystery, intertwining their journey with the parallel story of my family as we puzzled over the cause of our many cancers. It wasn’t something I had planned to do. By all rights, I always figured that if anyone wrote about this and the devastating effect it had on our family, it should have been Paul who, along with his son, bore so much of the burden, while I and my children were spared. With him gone, I felt compelled to write it.
As I continued delving into my research, I kept in mind the looming date of July 10, 2021, when I would have outlived all the members of my immediate family. To commemorate my parents and siblings, I wanted to do something that would make me viscerally feel alive and experience the wonder of the world in relative solitude. I considered hiking in the stark beauty of Joshua Tree National Park, sea kayaking off the Pacific coast, taking a hot air balloon ride, or walking in a forest of giant sequoias, which can live for 3,000 years.
In the end, I decided to take a flight in a tiny two-seat gyrocopter — think of a flying contraption not much bigger than a large motorcycle — over the Southern California coastline. Or, as my wife, Vicki, put it, “So you’re going to celebrate becoming the longest-living member of your family by putting your life at risk?” Admittedly, a good line, but I was undeterred.
Soaring a couple of thousand feet above the waves on that brilliant sunny morning, I felt a rush of adrenaline and some exhilarating moments (and one or two stomach-churning ones, too). I’d like to think it would make my mom and dad, my brother and my sisters, smile if they knew that I chose to do something just a little bit wacky on this day. For them, and for me. For us. Because they couldn’t.
Lawrence Ingrassia, a former senior editor at the New York Times, Wall Street Journal, and Los Angeles Times, is writing a book with the working title “A Cancer in My Family” scheduled for publication in late 2023 by Henry Holt & Company.
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