When courage is the cure

One family's battle with a rare stomach cancer shows the great promise and hard realities of gene science

Karen Chelcun Schreiber of Madison, Wis., had surgery at Massachusetts General Hospital to remove her stomach. (Wiqan Ang for the Boston Globe)

Her mother died from stomach cancer at the age of 52.

Her brother was stricken with the same disease at 56.

Bad luck or bad genes, Karen Chelcun Schreiber wondered. A blood test gave her the answer: She carried an inherited gene that made it likely that someday she, too, would develop a form of cancer that moves with devastating stealth and speed.

So Schreiber, a 50-year-old from Madison, Wis., traveled to Boston last month to have her stomach removed - in the name of prevention - a life-altering measure taken without hesitation by a woman whose determination was forged in the crucible of loss.

She almost certainly is not the last in her family to endure the surgery, the best hope for stopping a rare cancer sewn into her clan's genes. One of her other brothers has tested positive, too. And one of her sons. And a niece and a nephew, and, perhaps, other relatives yet to be screened.

The story of Schreiber and her family is the story of cancer and genetics in the 21st century, as an avalanche of genomic information confronts a growing number of families with wrenching decisions about how much they want to know, when they want to know it, and what they should do.

"The question is, how much of a gambler are you? I am certainly not willing to gamble with my life," said Schreiber, eyes animated, voice strong less than three weeks after surgery at the Massachusetts General Hospital Cancer Center. "All I know is 83 percent - that was my chance of getting cancer. That was enough for me."

For most of human history, our genetic recipe remained a mystery. But genomic research has advanced dramatically in recent years, yielding clue after clue about why some people come down with life-threatening illnesses and others don't.

Consider breast cancer. Scientists have identified genes that can so powerfully predict some women's odds of developing the disease that patients choose to have their breasts removed before cancer can strike.

"In the area of genetics and prevention, everything is an option," said Dr. Banu Arun, a specialist in cancer genetics at the M.D. Anderson Cancer Center in Houston. "We as healthcare providers do not tell them, 'Do this, do that.' It's a very personal decision."

There was no such choice for Elaine Chelcun, Schreiber's mother, when she was diagnosed with stomach cancer in 1982 and died within months. It would be 16 years before the genetic roots of the disease were discovered, nearly 9,000 miles away in New Zealand.

For decades, members of an indigenous community known as the Maoris watched with alarm as stomach cancer swept through, killing at least one person a year. At first, elders feared it was a curse imposed for the desecration of a burial ground. Later, they began to suspect that it was something amiss in their genes.

So in the mid-1990s they sought out a scientist to help uncover their secret and, just maybe, stop their suffering. They found Parry Guilford, a specialist in molecular genetics at the University of Otago in Dunedin, New Zealand.

Guilford and his colleagues collected blood from the living and examined tissue from the dead, looking for a genetic fingerprint shared by those with stomach cancer. Far faster than they expected - in less than two years - they identified the culprit: a mutation in a gene called E-cadherin, which also elevates the risk of breast cancer.

"It was a family under incredible pressure - there was no expectation to live a long life," Guilford said in a telephone interview from his office. "As one of the senior guys said when we found the gene, now the nightmare is almost over."

The nightmare would begin anew for the Chelcun family in 2007.

Greg Chelcun, Schreiber's older brother, was months away from retiring as a high school math teacher when he started experiencing intestinal problems.

Immediately, he thought of his mother. Immediately, he thought of stomach cancer. Doctors were dubious. After all, they said, stomach cancer is rare. What's the chance it would strike twice in the same family?

The symptoms persisted. Tests showed no evidence of cancer. His gallbladder was removed, providing temporary relief before Chelcun fell dreadfully ill and wound up in an emergency room and then an operating room.

Diagnosis: advanced stomach cancer.

In some people with the disease, cancer cells clump together to form a protruding mass. Chelcun had a different kind, which burrows just beneath the stomach's lining, making it especially tricky to diagnose until the cancer has already spread.

Chelcun's wife and Schreiber took to the Internet and happened upon medical reports describing something known as hereditary diffuse gastric cancer. It is so rare that doctors suspect only 100 families in the United States harbor the genetic mutation that sparks the disease.

Chelcun was tested first. Positive. The implications were clear.

"For me to go through this is one thing," said Chelcun, whose cancer is being kept in check by chemotherapy. "But to think that now the whole family is going to be at risk was almost worse."

Schreiber knew right away she wanted to be screened. A genetic counselor called with the results as Schreiber stood in a Milwaukee mall. Positive, like her brother.

Schreiber, who retired three years ago from her job in technology and accounting at a law firm, knew what that meant: She would have her stomach removed. She chose Dr. Sam Yoon to perform the operation at Mass. General, where six patients had already undergone the preventive procedure.

"All my patients, they've been profoundly affected by losing their parents, brothers, and sisters to this," Yoon said. "Everyone who's come to talk about surgery has wound up getting surgery."

The Sept. 12 operation, paid for by Schreiber's health insurance, lasted a little more than three hours. Yoon removed her stomach and connected her esophagus directly to her intestines in a delicate plumbing job that involved moving part of the gut.

"I didn't know before this that a person could live without a stomach," Schreiber said.

The stomach acts principally as a storage vessel, allowing food to slowly drain into the intestines. In patients such as Schreiber, the small intestine assumes that role, slowing the transit of food so that it can be digested.

At first she is limited to soft foods. Eventually, her diet will resemble what it was before the surgery - but she will have to eat smaller meals punctuated by snacks and, if she's like the typical patient, she may lose up to 20 percent of her weight.

So far, six members of the family have been screened. All have tested positive. When she got her result, Johanna Chelcun, Greg Chelcun's 24-year-old daughter, remained stoic until realizing what it meant for her hopes of becoming a mother. If her stomach were removed, it would be difficult to get enough nutrition to support a pregnancy.

"That was the only point in my appointment with my genetic counselor that I cried," she recalled. She has decided to put off the operation for now, but if she does have a child, there's a 50-50 chance the baby will inherit the mutation.

In contrast, her cousin Dan Crawford, who is eight years older and Schreiber's son, said he plans to have stomach surgery within two years. Men with the mutation are slightly less likely than women to develop cancer, but their risk remains high.

In the case of his mother, Schreiber's stomach was examined after removal by a specialist in gastrointestinal pathology. Dr. Gregory Lauwers made 174 slides containing pieces of the stomach, so that he could examine it in minute detail under a microscope.

At three spots, he saw the traces of trouble: Small, but unmistakable, it was cancer in its infancy. But, he said, they got it, all of it.

Stephen Smith can be reached at stsmith@globe.com.