This book is a combination of a thorough history of the study of genetics as a role in developing cancer with the personal tragedies the author's family has suffered, with an exorbitant number of cancer diagnoses at a very young age. There is much more scientific vernacular than I expected, which I was able to comprehend because of my scientific background in biology and currently working for a biopharma company, but that may not be the case for all readers of memoirs.

The story is a riveting one, and it details the significant progress that has been made in this field in a compelling narrative fashion. We learn about the role of heredity, the search for specific gene mutations, and the advances made in treatment for cancer patients. The author also weaves in stories about his immediate family and the ways this particular gene mutation has greatly affected their lives. It is a beautiful depiction of his family story as well as a profoundly informative and well-researched account of cancer research.

A Fatal Inheritance: How a Family Misfortune Revealed a Deadly Medical Mystery by Lawrence Ingrassia is a journalist’s look at how disease ravaged his own family. This book is a fascinating look at how scientists are learning about cancer’s genetic tendencies. Ultimately, this book is sad at the author’s family’s misfortune but hopeful in the possibility of preventing some of such tragedy in the future. I received a digital copy of this book from the publisher with no obligations. These opinions are entirely my own.

I will always enjoy taking in non fiction via audio. This book accompanied me on many trips to the grocery store and hours cleaning my sweet home.

Lawrence Ingrassia is not only a journalist, but a subject matter in his book. He comes from a family that has been greatly impacted by cancer and through telling his family's story he is able to share how cancer research slowly came about to find that there is some hereditary nature and some testing for genes to predict if a patient is more prone to developing cancer then others.

There were so many moments when I was reading this book that I kept remembering that this research was happening during my lifetime and I was so disappointed at the many lives that were affected by the slow progress of research. AND those many people that didn't know about the preventative tests that could have given them information where they could have made different decisions with their lives. When we are in a time where information is swirling 24/7 at the highest speed, to know that there is medical information not getting into the hands that need it, was sad to read about.

After finishing this book, it made me want to look and find more non fiction medical books to dive into.

I read the audiobook version of this one and the narrator was great. He shared the story with feeling and compassion in providing very difficult stories of these families who have been so gravely impacted by cancer.

A Fatal Inheritance is a well written layman accessible real life medical mystery/thriller by Lawrence Ingrassia. Released 14th May 2024 by Henry Holt & co., it's 320 pages and is available in hardcover, audio, and ebook formats. It's worth noting that the ebook format has a handy interactive table of contents as well as interactive links and references throughout.

Cancer research and our body of knowledge is expanding constantly. Obviously for patients affected by cancer and their families progress feels insufficient and slow. This is the background story of Li-Frameni syndrome, a genetic flaw with the P53 tumor supressor gene. Much of the book concerns the author's own family; he's the only one of 4 siblings who didn't inherit the flaw and his siblings died young, one after another.

Part of the book contains case histories of other families. It's a poignant and difficult read in places. It's meticulously researched and annotated throughout. The links and chapter notes will provide readers with hours of further reading.

Four and a half stars. This would be an excellent choice for public library acquisition, book club review, or non-fiction readers. For readers who enjoyed The Immortal Life of Henrietta Lacks and Being Mortal, this selection will likely appeal as well.

Disclosure: I received an ARC at no cost from the author/publisher for review purposes.

Fatal Inheritance is both an extensively-researched account of 60 years of cancer research and a heartbreaking memoir about the legacy of cancer in the author’s family. This book is fascinating and devastating. My mother had three different primary cancers before she died in 2012. Her third cancer, peritoneal, was incurable, with a survival rate of 12-18 months. Fortunately, she was able to be part of a phase two drug trial, and at the time of her death, she was one of two patients who had been on the drug for more than 100 weeks. Targeted therapy kept the cancer at bay for as long as it could, and she loved almost three years after her diagnosis. I felt very connected to the author’s story and to the other families whose painful experiences paved the way for a better understanding of the causes of cancer and more sophisticated ways of treatment. I’m grateful to NetGalley and Henry Holt for the opportunity to read and review the digital ARC.

This was nonfiction with a connection to the author and well done and well explained the scientific parts

This was a fascinating and interesting story about hereditary cancer. I liked that while it was interesting and informative, the importance of being screened, how it was discovered, etc was also highlighted well.

4.5 stars

Cancer is a disease in which some of the body’s cells grow uncontrollably and spread to other parts of the anatomy. Cancer often manifests as tumors, and the earliest mention of breast tumors occurred over 5,000 years ago, in papyrus documents from ancient Egypt. The illness was named by the ancient Greek physician Hippocrates in 370 BCE, who called the lumps karkinomas (carcinomas).

Over the years, cancer has been attributed to a variety of factors, including viruses, environmental carcinogens, chemicals, smoking, sunlight, diet, and more. Heredity was also suggested as a causative factor, but most medical researchers dismissed the idea until Dr. Frederick Pei Li and Dr. Joseph Fraumeni Jr. demonstrated that some families have an unusually high incidence of cancer, and that a propensity for the disease is inherited.

The author, award-winning journalist Lawrence Ingrassia, comes from a cancer-prone family. Ingrassia lost his mother Regina to breast cancer when she was 42; his sister Angela to abdominal cancer at age 24; and his sister Gina to lung cancer at age 32. Ingrassia's nephew Charlie, who got his first cancer at age two and later had a cancerous leg amputated, died at age 39; and Ingrassia's brother - Pulitzer-Prize winning reporter Paul Ingrassia (Charlie's father) - developed several different cancers and died at age 69. Lawrence's father Angelo worked as a research scientist, and - for a long time - the family thought their cancers might be related to chemicals Angelo brought home on his clothes. Later, the Ingrassias learned their family carried a faulty gene.

Heredity wasn't on the radar as a factor in cancer until Dr. Frederick Pei Li and Dr. Joseph Fraumeni Jr. began working together at the National Cancer Institute in Maryland. In 1966, the two researchers came across the unusual case of Ned and Darrel Kilius. At age 23, Ned was diagnosed with leukemia and soon afterward his ten-month-old son Darrel developed a soft-tissue tumor called a rhabdomyosarcoma on his arm. When Li and Fraumeni looked into the Kilius family tree (with the help of Ned's mother Irma), they discovered the clan was unusually susceptible to malignancies.

The scientists learned that Ned's uncle Charles and cousin Joyce died of lung cancer, and even more significantly, Charles' baby grandson Michael had had a soft tissue rhabdomyosarcoma in his shoulder. Ingrassia writes, "Li and Fraumeni were astonished: Not only did there seem to be a lot of cancers in the [Kilius] family, but two second cousins had been diagnosed as babies with the same rare soft-tissue cancer. That was virtually unheard of.....There are only five cases of rhabdomyosarcoma reported annually for every one million children in the United States."

To make a long story short, Ned Killius died at age 24, and Li and Fraumeni continued to collect information and medical records for the Kilius clan. The numerous malignancies in the family convinced the scientists their cancers were hereditary. Li and Fraumeni also located other cancer-ridden families, and expanded their studies to include them. As a result, the researchers became even more convinced of a genetic factor in certain groups. Li and Fraumeni published scientific papers in 1969 and 1975, and presented their research at genetics conferences, but were met with skepticism from most cancer researchers. Nevertheless, a few additional scientists jumped onto the 'hereditary factor' bandwagon, and more and more evidence accumulated.

Finally, in 1982, "English cancer researchers who also were studying families with high levels of cancer published a paper that credited Li and Fraumeni for their groundbreaking work by naming the suspected syndrome after them for the first time. The article they wrote for the 'Journal of Medical Genetics' was titled 'Two Families with the Li-Fraumeni Cancer Family Syndrome'."

Once heredity was identified as a factor in some cancers, genetics researchers were hot on the trail of the gene that caused the ilnesses. Two scientists - Arnold Levine in America and David Lane in England - eventually zeroed in on the same gene, TP53 (called p53). Researchers learned that p53 was not an oncogene (a gene that causes cancer) but rather an anti-oncogene (a gene that suppresses cancer). "Rather than causing cancer, p53's normal function was both to prevent cells from becoming malignant and even to kill cancerous cells.....The mutation in p53 somehow turned off the gene's cancer-fighting powers, thus increasing the likelihood of tumors developing."

This ground-breaking discovery led to the search for cancer treatments and medicines, and raised the specter of testing individuals in Li-Fraumeni families for the defective p53 gene. Affected individuals generally pass the 'bad gene' to half their offspring, and some people want to know if they have it, while others don't. The problem is, since there's currently no 'cure' for the p53 gene, how does it help to know you have it? And should you have children if you know you're a carrier? Ingrassia addresses these issues generally, and as they relate to his own extended family.

Ingrassia also mentions another inherited cancer gene, called BRCA, which is linked to breast cancer. Women who carry the BRCA gene are at high risk for breast tumors, and for these females, knowing they have the gene may be beneficial. Ingrassia doesn't mention this in the book, but actress Angelina Jolie underwent a double mastectomy when she learned she has the BRCA1 gene. She's said her chances of developing breast cancer have now dropped from 87% to under 5%.

To summarize, Ingrassia writes a good bit about Li-Fraumeni families; the search for ways to prevent, treat, and cure cancer; start ups and Big Pharma; and more. The author also includes numerous anecdotes about the backgrounds and personal lives of the people involved - patients and scientists alike - so we get to know and care about them.

Ingrassia's family - and their battles with cancer - inspired the author to write this book, and their tales are liberally interspersed throughout the narrative. These stories are inspirational, moving, and heartbreaking. The Ingrassia family embraces the phrase "Fight Like Charlie", for Charlie Ingrassia, who began his battle with cancer when he was two-years-old, fought one malignancy after another all his life, and sadly succumbed at age thirty-nine.

This is an important book for many reasons, one of them being that some physicians still aren't familiar with Li-Fraumeni Syndrome. This can be remedied, in part, by gatherings like Li-Fraumeni Syndrome Awareness Day.

We have reason to be optimistic, because researchers and doctors have made great strides in combatting cancer, and the hard work continues every day.

Thanks to Netgalley, Lawrence Ingrassia, and Henry Holt & Company for a copy of the book.

A difficult book to read but also a great one. How much loss can one family have before they start trying to find out if there's something more to their DNA? Fantastically written and researched.

This is so much more than a memoir. The author's mother passes away at age 42 of breast cancer that she has been battling for a decade. There seemed to be a lot of cancer in his family but was it just bad luck. He weaves the story of his family and losing close family members with the finding of a rare mutation. Frederick Li and Joseph Fraumeni have this syndrome named after them. After coming across the Kilius family when both father and infant son are diagnosed and fighting cancer. In tracing their family history they find a line of cancer diagnoses. They do life long research into trying to identify the cause of the cancers and eventually into the genetics.

Perhaps because Mr. Ingrassia is a journalist and not a medical professional he was able to tell the story of his family and the others with hope and compassion and making the science easy to understand.

Thank you to Netgalley and Henry Holt for providing me with this digital copy.

A Fatal Inheritance is a fantastically researched journey through one of the most terrifying realities of today's world, cancer, and how it runs in some families and yet not others. Trying to unlock the code of why some members within a family get cancer, and others don't, but also more specifically why some families have clusters of cancers, meaning more than one cancer for one family member, compounded within the genetic line. This is the story of not only the families being researched because of the anomaly of how many cancers their family seems to have, but also the doctors and their drive to not only find the answers as to why this is happening, but also how to make it stop. Fascinating deep dive into genetics, but in a way that is very readable and understandable to anyone. The more we study and learn about the human body and genetics, the more I am surprised at how little we have really covered and how much more there is still yet to learn.
*I received a copy of this book from NetGalley. This review is my own opinion*

There are many reviews of this book that will be better than this one - if you are looking for a comprehensive break down of this magnificent book, those will be perfect for you [and I encourage you to seek them out]. THIS review is written, quite simply, from pure emotion.

My heart immediately broke for the author - I cannot even imagine losing almost all of my family over the years [starting with his Mom when he was 10 {I believe} ], and his story alone is devastating and heartbreaking.

THEN, he takes you down the rabbit hole of the discovery of genetic cancer [Li-Fraumeni Syndrome] and the endless [and often seemingly hopeless] work those men [Dr. Frederick Pei Li and Dr. Joseph Fraumeni Jr., whom the syndrome is named after] and ALL the amazing Dr.s that have come [and continue to come] since, in search of a cure [and a why].

We also meet the families afflicted with this syndrome [especially "Family A", who are essentially ground zero in this story], and on the emotions that flowed then. The amount of cancer and death amongst these families is unfathomable, and by the end of the book, you will be as dry as a desert from all the tears you have shed. And them you read the final chapter and just when you think you cannot cry one more year the ending will completely wreck you and you will never look at your family and those around you that you love the same way again.

I was privileged to receive an audiobook ARC and I am so glad I did - the narrator [now one of my favorites] did an excellent job and even his voice broke at times at the sorrow being played out in these pages. His own humanity added to the story and made it that much better.
I must also compliment the narrator's ability to whip off all the medical terms correctly, even in the emotional parts. Some of the tests [and research] and cancer names are tongue -twisting on a good day, and Mr. Wayne handled them with dexterity and perfection. Very well done.

#fightlikecharlie

Thank you to NetGalley, Lawrence Ingrassia, Roger Wayne - Narrator, Henry Holt & Company, and Macmillan Audio for providing the eBook and audiobook ARC's in exchange for an honest review.

I learned a lot about how they figured out some cancers are genetic. The stories about the specific people affected by gene mutations made this a readable nonfiction story.

https://www.goodreads.com/review/show/6475027035

Fascinating. Ingrassia, partly because he's wound his own family history into his work, has written an accessible and informative volume about cancer research. Thanks to Netgalley for the ARC. It was an unexpectedly engrossing read,

“A heartbreaking story of family loss and an inspiring story of scientific achievement”
The quote above is author Lawrence Ingrassia’s summary description of cancer research during the last six decades, especially the Li-Fraumeni syndrome that is the focus of A Fatal Inheritance. It is also an excellent description of his book, which was outstanding on both topics and which I would recommend to a very broad audience.
The stories of the families who experience the results of their “fatal inheritance” were heartbreaking even for me, and I do not know any of the people affected. It is hard to imagine being a member of the family and living through it, and I suspect that the author, who DID live through it in his own family, shed more than one tear as he wrote them. The illnesses and deaths are hard to take, such as the eight-year-old girl battling her second cancer, but there are also other understandable but perhaps less expected episodes. I was touched by a father recommending that his son, who had experienced several cancers growing up and lost several relatives to cancers, not marry and have children. The son responds that if his father had done that he himself would not be sitting there that day! In another family with widespread cancer a woman happily tells her family that a test has shown she does not have the gene in question only to be greeted with anger by her cousin’s obviously envious husband.
The descriptions of the scientific research, controversies, and discoveries were equally compelling. For a layperson like me, the heat of the disputes between the scientists who were pursuing genetic connections to cancer and those who were certain the cancers were caused by viruses was fascinating and eye-opening. I learned quite a bit about the subject, which was presented in a way that readers unfamiliar with this field of biology can understand, but I did not feel, as I often do, that the author was talking down to me. It made me smile and admire the researchers even more to read about their gathering of data like family histories in the years before the internet and largescale computers simplified such pursuits to such a degree that we tend today to take it for granted. Also impressive was the cost of such research, e.g., Warner Lambert pledged FORTY million dollars to help pay for simply the last phase of clinical trials for a test of a new drug.
Having a family member develop cancer is difficult for any family. The distress caused when multiple members suffer and often die from cancer is hard to imagine, especially when the cancer develops in young children, as it often does in Li-Fraumeni syndrome. I thank the author for sharing his family’s story and for educating readers like me on the connection between genes and cancer.
I received an advance review copy of A Fatal Inheritance from NetGalley and Henry Holt and Company.

This was a well written memoir as well as a history of cancer research. The author shares his personal family story of cancer in his family, intertwined with other families' stories of cancers occurring through out the family, and the history of researchers attempt to document and research why some families share a cancer trait. While the topic is hard, the author is able to show the power of research and medical advances to demonstrate hope for future generations. Interesting read.

Truthfully, I was reluctant to start this book after requesting it from the publisher through NetGalley for two reasons. I didn’t want to read a highly technical book like ‘ Code Breaker’ ( which I read but sludged through, UGH ). And I was concerned it might be overwhelmingly filled with grief and despair.
It was neither .
Initially, I was intrigued by the title, cover and premise of this book… and my intrigue was held through to the end of the book. The cover seems to illustrate ( literally) that the book is about a family… and yes, it’s about several families plagued with numerous multi-generational cancer diagnoses.
It’s easily digestible material, heavily peppered with stories of several families plagued by all too frequent, all too early ( childhood for example ) diagnosis through multi-generations of the families. The book starts off in personal and compelling tales that immediately drew me in and never felt overwhelmingly sad or lacking in purpose. The personal stories are hard to read about yet that’s the point… Cancer doesn’t discriminate but in this book’s stories it does crop up, often times with one family member getting a cancer diagnosis more than once ( sometimes several times ) through their lifetime… however long or short their life is.
I didn’t find the book as emotionally wrenching as one might think because the medical research elements help bring clarity and purpose to the more personal stories within the book. My interest never let up while reading the book and I found it easy and compelling to come back to each day. Educational, informative and engaging…

Thank you to the Publisher and NetGalley for the ARC of this novel. This book was difficult to read with the large group of people referenced, it was a bit too dry although it is a fascinating subject and you feel greatly for the families involved.

Many thanks to NetGalley and Henry Holt Publishers for the advance ebook copy of “A Fatal Inheritance” by Lawrence Ingrassia. Ingrassia interweaves his family’s tragic medical history, including the loss of his mother, his two sisters, his brother, and his nephew to cancer; with the scientific hunt for the causes of familial cancers. It was initially thought that familial cancers might be linked to viruses, environmental triggers; or a variety of other causes; but a team of determined researchers spent decades fighting professional disdain to unravel the DNA linkage that would expose the real cause of many familial cancers - mutations in DNA. This in turn would lead to the ability to test for these gene mutations, including the breast cancer genes BRAC1 and BRAC2. An incredibly compelling tale, I raced thru this book as one who - like millions of other Americans - has had family members affected by cancer: my husband and I lost 3 of our 4 parents to cancer. The chapters alternate between the scientific research, which might seem dense to the casual reader without a scientific or medical background, and the deeply affecting portions about Mr. ingrassia’s family. I would highly recommend to those with an interest in science and/or medicine as well as those with family’s affected by cancer.

A Fatal Inheritance: How a Family Misfortune Revealed a Deadly Medical Mystery by Lawrence Ingrassia is a very highly recommended deeply personal memoir of a family's medical tragedies merged with a medical thriller of cancer research as scientists work to discover answers.

Lawrence Ingrassia's family story is one where death from cancer is prevalent. In his family Ingrassia lost his mother, two sisters, brother, and nephew to different kinds of cancer at different points in their lives. In the 1960s his family became one of several that intrigued Dr. Frederick Pei Li and Dr. Joseph Fraumeni Jr. in their research into why some families experienced so many deaths by cancer. They began collecting records and analyzing data to understand cancer clusters in some families.

They published their results in a paper which showed that there was likely a genetic component involved and this discovery was named the Li–Fraumani Syndrome. Their paper was first published in the American Journal of Epidemiology, and wasn't widely known. Later genetic researchers were intrigued by the syndrome and with help from Li and Fraumani and the samples they collected from families they were able to discover a mutation in the p53 gene. This inherited mutation is responsible for the higher risk of cancer. Its discovery was groundbreaking in cancer research and offers hope for potential future research.

Ingassia does an excellent job sharing his family's and others deeply personal and emotional stories while also covering how the cancer research of Li and Fraumeni’s and others evolved. The merging of the personal tragedies with the ground breaking discoveries work well together and help create a tension and anticipation for some hopeful discovery for a future cure. The question of genetic research in regards to ethical considerations and personal privacy is also considered. Thanks to Henry Holt & Company for providing me with an advance reader's copy via NetGalley. My review is voluntary and expresses my honest opinion.

The review will be published on BookBrowseBarnes & Noble and Amazon.