Review of "A Fatal Inheritance: How a Family Misfortune Revealed a Deadly Medical Mystery" by Lawrence Ingrassia

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).


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

Review of "Slough House: Slough House #7" by Mick Herron

This is the 7th book in Mick Herron's 'Slough House' (Slow Horses) series, about British MI5 agents who've made a serious mistake and are relegated to working in a dilapidated building called Slough House. The novels in this series are best read in order because of the continuing story arc.



*****

The man in charge of Slough House is former spy master Jackson Lamb, an offensive slob who slings insults at people, smokes too much, eats too much, and has terrible hygiene. Regardless, Lamb feels compelled to look out for his 'joes' (agents), even if he thinks they're idiots.



By now Diana Taverner has been first chair at Regents Park for a while, and she's a force to be reckoned with. Unfortunately, Lady Di's ambition, hubris, and impatience led her to make a big mistake.



The Russians had used the nerve agent Novichok to kill a person on British soil, so Diana retaliated by engineering an assassination in Russia.



To finance the hit, Diana (secretly) took money from a cabal of wealthy British citizens, and two members of the syndicate, politically ambitious Peter Judd.....



.....and media tycoon Damien Cantor, seem to think Diana owes them - and they're not shy about asking for favors.



Diana has pulled another shady stunt as well. She's 'disappeared' Slough House and all its personnel from Regents Park's records, and hasn't explained why. Meanwhile, some of the slow horses notice they're being followed, and two former slow horses have been murdered. It's clear Jackson Lamb and his joes need to take some action.



In the meantime, the slow horses stay true to form. Catherine Standish hands out/organizes the boring assignments created by Lamb - like making lists of people who borrow 'suspicious' library books;



River Cartwright ditches his paperwork, but races into action when necessary;



Louisa Guy tries to follow the rules more than most of the slow horses;



Lech Wicinski makes it his business to suss out who's following him;



Shirley Dander's cocaine addiction and hot temper cause trouble;



and Roddy Ho makes us laugh with his deluded narcissism, but does good work with his computer hacking skills.



There's plenty of action in this book, and some big surprises. This thriller is a must read or fans of the series.

Rating: 4 stars

Review of "The New Couple in 5B: A Novel of Suspense" by Lisa Unger

Rosie and Chad Lowan are young marrieds living in the Village in New York City.

Rosie is a writer and Chad is an actor, and the couple - though struggling financially - take the time to care for Chad's dying Uncle Ivan.



Ivan resides in the Windermere - a luxury NYC apartment building with a reputation for supernatural occurrences, murders, and suicides.



When Uncle Ivan dies, Rosie and Chad are surprised to discover that Ivan cut his daughter Dana out of his will and left his Windermere apartment (5B) - worth millions of dollars - to them.



When the Lowans move in, Rosie immediately starts to feel uncomfortable about the intrusive neighbors; the ubiquitous surveillance cameras; the Alexa-like intercom system; and the general atmosphere of 'big brother is watching you.



Rosie also thinks she might have encountered a ghost boy in the basement.



Bad things start to happen, and the story is fairly predictable from there.

For me this book is too slow and too reminiscent of Rosemary’s Baby by Ira Levin. Also, I don't like books where the female protagonist is too naive to see what's right in front of her eyes. In other words, TSTL (too stupid to live).

This isn't a bad book and many suspense fans would probably enjoy it. It's just too derivative for me.

Rating: 3 stars

Review of "Oye: A Novel" by Melissa Mogollon

Most of this tragicomic novel is composed of phone conversations between Miami high school senior Luciana Domínguez.....

.....and her sister Mari, a sophomore at George Washington University in Washington, D.C. We only 'hear' Luciana's side of the conversation, interspersed with occasional remarks to or from other people.



The phone conversations tell us a lot about Luciana and her family, who come from Colombia.

Luciana has been an indifferent student since freshman year, and now worries she won't get into college. She's attracted to girls, and recalls the scene when she came out to her mother: "[Mom] literally threw herself on the floor, grabbed my foot, and started stomping on her own neck with it saying. WHO. YOU. ARE. IS. KILLING. ME."



Luciana is a little overweight, and her mother Elena - who's well-meaning but annoying - constantly advocates exercise and a better diet. Luciana has never had a romantic relationship; has a gay best friend called Nico; and in many ways, is the steel center of the family.



As the story opens, it's September 2017 and Hurricane Irma is threatening Florida. Luciana and her mother are preparing to evacuate, and Luciana tells Mari that Dad has to stay in Miami to work.....



.....and Abue (grandma) can't be convinced to evacuate with them, no matter how much Luciana and her mother cajole, beg, persuade, and bribe the septuagenarian.



After some back and forth talk about Abue's safety, Luciana tells Mari, "FINE. Then just call and confess that she needs to evacuate so you don't feel guilty over not being home. THERE. I SAID IT..... We were invisible to you until Irma found us. But now you desperately need Abue to stay safe, so you don't have to come back or feel guilty if something happens."



This exchange presages Mari's ongoing behavior, which is to put her sorority sisters and college activities ahead of the family at every turn, much to Luciana's anger and dismay.

We learn that 75-year old Abue is determined to be seen as glamorous, beautiful, and affluent at all times. Abue had plastic surgery on her face, boobs, and butt; insists on always having perfect hair and makeup; dresses provocatively; has lots of boyfriends; puts her Publix groceries into Whole Foods bags to fool the neighbors; and wouldn't let the plumber fix her broken toilet for a month, because she'd dyed her hair the wrong color and was waiting for it to grow out.



In any case, Luciana and her mother flee from the hurricane and have an adventurous trip. Along the way they stop at the home of Cousin Susana, and Luciana tells Mari, "The second we got in, Mom started just randomly telling Susana about how she doesn't agree with the IUD treatment that my doctor suggested for my endometriosis....But she kept calling the IUD a DUI. And Susana's face was getting more and more worried, as Mom started walking around saying: Luciana's DUI this! And Luciana's DUI that!" (Afterwards, Luciana had to explain she wasn't an alcoholic.)



When the hurricane danger passes, Luciana and Elena return to Miami and are shocked to find Abue sick and jaundiced in her apartment. It seems Abue refused to evacuate because she was (secretly) feeling ill.



This starts the more serious part of the novel, where Abue is found to have a tumor that requires surgery and ongoing medical care. The narrative from this point on is both sober and amusing. For instance, the doctor tells the family "The surgery is going to be high risk....the tumor is beginning to obstruct her functions....this mass might be malignant....she will likely need chemo....etc." The diagnosis is devastating, and Luciana - who's especially close to her grandmother - makes herself the advocate for Abue, and looks out for Abue's best interests.



The family doesn't tell Abue how serious her condition is, and Abue walks around the hospital like a peacock strutting her feathers up and down the halls. The nurses think Abue is perfectly fine and hilarious, and Luciana tells Mari, "The only person that understands the situation at hand is this Haitian nurse named Junior. He loves to discuss astrology, and practice his Spanish with her. And he knows that Abue's performance is one whole long con. Junior even calls her 'diosa' (goddess) whenever he walks in 'Hola hola, diosa. How is my diosa goddess today'....She probably thinks the tumor is worth it....just for that."



Be that as it may, Abue needs home care between hospital stays, and she's installed in the Domínguez household, in Luciana's room. Abue's sister Luisa - whom Abue hates and hasn't seen in decades - volunteers to come help.



Luisa's visit provides some of the more revealing moments in the book. For example, we hear that Abue threatened to throw Luisa out the window if she ever actually came to visit; Abue tried to change her phone number when Luisa called to say happy birthday; and Abue insists Luisa planted the tumor decades ago...probably as a favor to their crooked mother.

The sibling visit doesn't actually go that badly, and it leads to revelations about Abue's early life in Colombia, which was difficult and sad.

The story moseys along through Thanksgiving, Christmas, and on into the next year, during which time Luciana takes care of Abue, and Abue reciprocates with affection and encouragement for Luciana. Luciana grows more confident as she finishes high school; plans for her future; tussles with Mari; and occasionally grabs Nico and goes to Ladies' Night - a club with a cute bartender.



I wouldn't call this a comic novel, but it has plenty of light moments in the midst of the drama. A fine debut, dedicated to all grandmothers.

Thanks to Netgalley, Melissa Mogollon, and Random House for a copy of the book.

Rating: 3.5 stars