A Fatal Inheritance  

by Larry Ingrassia

What happens when your mother, three siblings and your nephew, all develop cancer? And almost all of them die at a young age? 

For Larry Ingrassia, the sole survivor of his family, it was an overwhelming and fatalistic feeling as well as a personal medical mystery. A former editor of the Wall Street Journal and New York Times, he finally decided to research and write a book about the disease that decimated his family.

A Fatal Inheritance was published in June, 2024.

Using journalistic traits of persistence, doggedness, and his empathetic interviewing skills, Ingrassia weaves a complex mystery story. He interviews survivors of families with multiple cancers who were originally studied and interviewed in 1969 because of their extraordinarily high cancer risk.

He reveals the story of how Drs. Frederick Li and Joseph Fraumeni from the National Cancer Institute Epidemiology branch suspected there was a genetic aberration in these families causing cancer. However, their initial paper in 1969 describing the affected families contradicted current thinking about cancer etiology. Viruses and environment were the causes of cancer proclaimed other scientists, not abnormal genes. 

Undeterred, these physician scientists persisted, and after 20 years of family studies, genetic, molecular and epidemiological analysis culminating at MIT, they discovered that these families had a mutation in the tumor suppressor gene called TP 53 that led to a very elevated risk of cancer, including sarcomas, brain, breast and many others occurring at very young ages.

This seminal discovery became the foundation on which studies of genetic susceptibility to cancer were built. And, it is now known that abnormalities in the TP53 tumor suppressor gene affects 60% of all cancers.

For an understanding of the intersection of family tragedy and scientific discovery, I highly recommend this book. For anyone whose family has had experience with cancer it is about finding an answer and hopefully someday, a cure.

Elaine Li Shiang MD

Author alert: 

Dr. Frederick Li is my late husband, a colleague of Dr. Joseph Fraumeni for whom Li Fraumeni Syndrome is named. 

Elaine’s extended family with the author in Cambridge