Genetics Provide One Family with a Death Sentence—and An Escape; Stanford Genetics Center, Preventive Surgery Help Save A Generation of the Bradfield Family

Business Wire, May 24, 2006

STANFORD, Calif. -- VIDEO: Footage of David Magnus, PhD, director of the Stanford Center for Biomedical Ethics, discussing the ethics of pre-emptive cancer surgery is available at http://mednews.stanford.edu/releases/2006/may/stomach-cancer.html

Golda Bradfield's death in 1960 from stomach cancer foreshadowed a legacy she would pass on to the next three generations of her family. She never knew that she had a mutation in a gene known as CDH1 that made stomach cancer almost inevitable. So far 21 of her 31 children, grandchildren and great-grandchildren have inherited that mutation.

Of Bradfield's seven children who unknowingly carried the CDH1 mutation, six died of stomach cancer, mostly in their 40s and 50s. It is not known whether the eighth child, who had no children, had the gene.

As Bradfield's 18 grandchildren watched their parents, aunts and uncles fall ill, the threat of stomach cancer seemed ever-present. "I felt like this big cloud was hovering over me since I was 13 when my mother was diagnosed," said Mike Slabaugh, Golda Bradfield's grandson who lives in Dallas. His mother died when he was 15. Because of that threat, Slabaugh said that he never married and never had children.

Despite his fears, Slabaugh is still alive, as are all but one of his 17 cousins. His generation's experience with cancer differed dramatically from that of their parents, who had little warning of when or if cancer might appear. Instead of living or dying at the whim of their genetics the cousins have turned recent genetic technology to their advantage. They have all been able to get tested for the CDH1 mutation.

For those who inherited the mutated version of the gene, knowledge means power. They had their stomachs removed before discovering signs of cancer, thus evading their genetic destiny.

The Bradfield family's experience with genetic testing is one that is becoming more common as research turns up increasing numbers of disease-causing genes. Groups such as the Cancer Genetics Clinic at the Stanford University School of Medicine now offer testing for many mutations and have projects under way to learn more about how to treat or prevent cancer in people who carry those mutations. According to assistant professor James Ford, MD, who leads the clinic, Stanford was among the first to begin counseling families with inherited genes that increase their chance of contracting stomach cancers--and offering some an operation to eliminate the risk of it ever occurring.

That was an offer the Bradfield cousins who tested positive for the CDH1 mutation accepted. Six of the cousins including Slabaugh had their stomachs removed at Stanford by surgeon Jeff Norton, MD. For them, as with others, testing meant an end to constant worries about the future. "The specter of gastric cancer is gone forever. When I wake up in the morning it's a day I wouldn't have had," Slabaugh said.

The Bradfield cousins and their families are meeting in Las Vegas on May 27 to celebrate overcoming the odds. For some, this reunion will be the first face-to-face meeting, despite regular e-mails and phone calls. In fact Linda Bradfield, one of the cousins who tested positive for the mutation, said the family only started communicating regularly after the diagnosis. "We weren't a close family," she said. "Its tied us together."

Stomach cancer has been known to run in families for centuries. In fact Napoleon Bonaparte's family is now thought to have carried the CDH1 mutation. However, it wasn't until 1998 that researchers in Australia discovered the gene in a New Zealand Maori family with extensive stomach cancer. Since then a few researchers around the world have begun offering testing for the mutation. Roughly 100 families have tested positive.

The CDH1 gene makes a protein called E-cadherin that normally dots the outside of cells, helping those cells bind to each other in a sheet. Golda Bradfield had one copy of the gene that made a normal E-cadherin protein and one that carried the mutation. Statistically speaking, each of her children had a 50/50 chance of inheriting either the mutated copy or the normal copy of the gene.

A family who tests together

The Bradfield cousins became aware that a mutation was responsible for their family's cancer risk in 2003 when the first cousin died of gastric cancer. His doctor sent a blood sample to David Huntsman at the University of British Columbia, who at the time was one of the few people offering a genetic test for mutations in the CDH1 gene.

Although the cousin had died by the time the result came back positive, his wife sent a letter to the remaining Bradfield relatives. In it she included information from UBC describing the CDH1 mutation and recommending genetic counseling for all family members.

Linda Bradfield in Anaheim Hills, Calif., was among the first to get tested. She and her sister Rita, visiting from Seattle, and third sister Stephanie from Newport Beach, Calif., had blood drawn on President's Day of 2004. Six weeks later they got the results. Rita and Linda were positive, Stephanie was not.