Family tree includes a genetic time bomb

Five months before dying of a rare form of stomach cancer, Sandra McNamara uncovered a devastating family legacy.

Her illness was closely linked to a genetic mutation. She had it, and that meant her three sisters and their children might have it too.

McNamara picked up the phone and started calling relatives in Chicago, Boston and Denver. You need to know: This cancer is hereditary, she said. Get tested.

The disclosure threw the family into turmoil as relatives evaluated their choices, including whether to have their stomachs surgically removed as a preventive measure.

Few families have grappled as dramatically or extensively with their genetic heritage as McNamara’s, though tests for other mutations, such as those linked to breast cancer, have been available for years. Many more people will find themselves in similarly wrenching situations in the years ahead as genetic tests proliferate and scientists learn more about the genetic basis of disease.

With advance knowledge of their potential destinies, people will ponder whether to share the information with parents, siblings and children and how best to respond to worrisome risks.

The story of McNamara’s family provides a glimpse of how complicated and life-changing these genetic revelations promise to be.

The threat in their case was hereditary diffuse gastric cancer, which hides in the stomach and forms small tumors scattered like needles in a haystack. That means it’s difficult to catch through screening, the way women try to find early breast cancer with a mammogram. By the time symptoms occur, the disease has typically reached a serious stage.

For people with the mutation, however, the alternative to screening is terrifying. The only current option to prevent this cancer is removal of the entire stomach -- an extraordinarily radical step, although it could save their lives.

Ultimately, McNamara’s family opted for genetic testing. Six female relatives learned they carried the stomach cancer mutation. Four of those six pursued stomach surgery; two opted for regular screenings. All are still confronting the consequences of their decisions.

Five sisters

McNamara was the second of five sisters, a dignified, religious woman who loved to paint and who had worked for years in human resources at Walgreen’s before retiring in Glenview, Ill.

The sisters knew there was cancer in the family. But when McNamara’s father died of stomach cancer in 1961, it was an illness people didn’t discuss. Fourteen years later, when one of her sisters died of the same disease, it seemed like a fluke.

In late 2004, McNamara was diagnosed with breast cancer. While still on chemotherapy, McNamara returned to Evanston Hospital with abdominal pains. Doctors discovered advanced stomach cancer.

Scott Weissman, a genetics counselor at the hospital, had a hunch McNamara might have hereditary diffuse gastric cancer, a rare condition identified only seven years earlier.

About 100 families of various ethnicities have been identified with this disease worldwide, said Dr. David Huntsman, a genetic pathologist at the British Columbia Cancer Agency in Canada.

Testing would show McNamara carried a telltale genetic mutation linked with the cancer. The mutation -- a coding error in the genetic software that resides in cells -- lies on the CDH1 gene, which is responsible for making a protein that binds cells together.

The implications were clear: McNamara’s father probably had the mutation, as did the daughter who died.

For the surviving sisters, this was a potentially deadly inheritance: 70% of people with the mutation develop hereditary diffuse gastric cancer by age 75, research shows. The only treatment is stomach-removal surgery, sometimes accompanied by chemotherapy and radiation.

Outcomes are dismal. According to Dr. Jennifer Obel, an Evanston Hospital oncologist, just 10% of patients with diffuse gastric cancer are alive five years after diagnosis.

Opting for test

Telling her family about the genetic mutation would be McNamara’s final gift -- an effort to save them from the suffering that awaited her.

Her three surviving sisters took the news in stride, aided by a large dose of denial. Still, all decided to get tested.

Linda Green, then 69 and living in Batavia, Ill., was sure she was OK -- but if, God forbid, there was a problem, she’d want her three kids to know.

In Denver, Judy Bulow, then 59, also was convinced she was safe. But she too wanted to know.

“I was hoping I wouldn’t have it; that I’d be fine,” said Martha Lassy, who lives in Geneva, Ill.

McNamara left it up to her sisters to disclose the medical discovery to their families. But she reached out to three members of the next generation: the children of her fourth sister, Bonnie Gosse, who had died of stomach cancer 30 years earlier, at age 33.

The news was overwhelming. “It brought back all the stuff from my childhood, when Mom died,” said Julie Gosse, who grew up in Elgin, Ill., and now lives in Denver.

“My initial feeling was shock. But this pulled the pieces of the puzzle together -- what had happened to my grandfather and my mom, and what was happening to my aunt,” said Julie’s brother, Jeff, who lives outside Chicago.

“I was completely devastated,” said Aimee Mury, Julie’s sister, who lives near Boston.

The parallels with the past were frightening. When her mom got sick, Mury was 5 and just starting kindergarten. Now, the oldest of Mury’s three children, Xander, was 4 and getting ready for school.

(The youngest generation has yet to be tested for the mutation.)

Over the summer of 2005 and into early fall, Mury couldn’t decide what to do. She began to get regular stomachaches. “I just couldn’t deal with it,” she said.

Death claimed her beloved Aunt Sandra in early November, and in the weeks that followed, Mury couldn’t fight off the anxiety. Terrible scenes rose in her dreams at night; during the day, she fought dizziness. A sense of doom was palpable, yet still she hadn’t gotten the genetic test.

“It hit me, what am I doing? I’ve got three little kids. I know how horrible this cancer is,” said Mury, 38 at the time. She made an appointment with a genetics counselor.

Fear confirmed

The test results confirmed the women’s worst fears: All three surviving sisters and their deceased sister’s daughters had the genetic mutation, which also significantly raises their risk of breast cancer.

Green got the call from Evanston Hospital four days before her sister died.

“I can’t tell you how devastating it is to know you have this awful, deadly disease in your family and now it could kill your children or your grandchildren or your sisters,” said Green.

In Chicago and Denver, doctors outlined a grim scenario. For unknown reasons, women with the mutation have a higher risk of contracting hereditary diffuse stomach cancer than men (83% vs. 67%).

That didn’t explain why all the men in McNamara’s extended family would test negative for the genetic aberration, however.

“We think that was random,” said Weissman, the genetics counselor.

Because existing screening methods aren’t very good at detecting the disease in its early stages, the best preventive measure available is total prophylactic gastrectomy -- removal of the patient’s stomach.

The person’s esophagus is then surgically attached directly to her intestines, affecting how and what she eats every day for the rest of her life.

Little long-term data exists about the consequences of this difficult surgery. Mostly, it’s been performed on older cancer patients near the end of their lives. At the time of the discussions, physicians in Chicago and Colorado hadn’t tried the surgery on patients with the family’s type of cancer.

The sisters in the older generation each weighed the alternatives. Bulow, a soft-spoken children’s book buyer, realized she couldn’t live with the threat of the disease and elected to go ahead with surgery.

Green and Lassy decided against it. Lassy said she spoke with half a dozen people who’d had stomach-removal surgery. Some had adapted well; others were having a hard time.

Lassy elected to be screened for cancer every six months.

Next generation

Hardest for the sisters was facing the possibility that they had conveyed the cancer threat to the next generation.

Green put off the discussion until Christmas 2005. “I have to tell you, I have that gene that killed Sandra,” she remembers announcing.

For her daughter Laura Ciezadlo, it was bad enough to get the awful news on the holiday. But for her mother to have waited almost two months to disclose her test results, that was worse.

Ciezadlo, a brisk, efficient woman, immediately arranged to be tested at Evanston Hospital. The outcome she hadn’t wanted to confront arrived when Weissman called her in for the results.

“The wind gets knocked out of you,” she said. “I just put my head down and wept.”

Her own daughters were 5 months and 2 at the time.

“You wonder, what if I wait five years -- will they come up with a cure for this cancer?”

With her husband, Ciezadlo spent the next two months doing research and consulting with medical experts in Chicago and elsewhere.

Gradually the family moved from denial to acceptance. Mury was the first to schedule stomach surgery, at Massachusetts General Hospital in April.

Julie Gosse, her sister, put off her own surgery at Northwestern Memorial Hospital until the fall, so she could help Mury through the operation first. Bulow, whose two children are adopted, and Ciezadlo also decided to undergo the procedure. Insurance covered the surgery.

The family exchanged information through frequent phone calls and a family blog. “We went from near silence to a great coming together and sharing,” said Mury.

Their choices

None of the women says she regrets having the surgery. But adapting was harder than they expected.

Eating becomes a regimented exercise rather than a pleasure, Ciezadlo said. Every one to two hours, you sit down for a snack and then drink half an hour later. Chewing is mandatory, at least 25 times every bite, to make digestion easier.

“Frankly, you never want to eat again,” Ciezadlo said.

For her, a typical day starts with toast and peanut butter at 6:30 a.m. Two hours later comes oatmeal, followed by half a cup of peanuts. Lunch is typically chicken and chips, followed in the afternoon by peanuts and a granola bar. Dinner is usually a hamburger or more chicken and cooked vegetables, with a handful of Teddy Grahams before bed.

There is a lot of physical discomfort, especially at the start. Gas pains and intestinal problems are common. At night, Ciezadlo sleeps on a wedge pillow elevated at 30 degrees to keep digestive fluids from surging back into her esophagus.

Bulow has had complications that sent her back to the hospital; she is still trying to recover her strength.

Mury dropped 17 pounds off her already slender frame and was weak for a long time. But she was lucky. Doctors found a cancer nodule in her stomach, a sign that she may have warded off disaster just in time.

Psychologically, it was hard to give up activities Mury had shared with her husband, such as rock climbing. Depression and anxiety flooded in as her body began to recover and she faced what had happened.

That meant confronting her mother’s untimely death again and all she had lost. “I had always feared that I would die young of cancer,” she said. “It was such a relief to think I don’t have to.”

She’s not the only one mulling over the matter. Mury said her daughter Jasmine, now 5, brought up the subject.

“Mommy, I’m really sorry your mommy died. She didn’t get to the hospital in time to get her owie out, did she?” the girl asked.

“Yes, that’s what happened,” Mury remembered responding. “But things are different with me. They found my owie and I’m just fine.”