Brain Tumor.
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.
Dr. Frederick Pei Li (left) and Dr. Joseph Fraumeni Jr..
The author, award-winning journalist Lawrence Ingrassia, comes from a cancer-prone family.
Author Lawrence Ingrassia.
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.
Regina and Angelo Ingrassia with (left to right) Gina, Lawrence, Angela, and Paul.
Regina Ingrassia with Paul and Lawrence.
Pulitzer-Prize winning reporter Paul Ingrassia.
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.
A rhabdomyosarcoma (soft tissue tumor) can start as a small bump
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.
Ned Kilius died at age 24
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).
Scientist Arnold Levine
Scientist David Lane
The p53 cancer gene
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.
The BRCA breast cancer gene
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%.
Actress Angelina Jolie had a double mastectomy to avoid contracting breast cancer
To summarize, in this very readable book 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.
Charlie Ingrassia
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.
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.
Rating: 4.5 stars
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