Stan Walker was seven when groundbreaking research revealed a genetic mutation was killing members of his family.

It was their work with scientists that led to the diagnosis of the faulty gene, saving hundreds of families around the world, and eventually Walker himself.

Alanah Eriksen looks at that science - and what is still to be done.

Ann Framp was a nurse at Tauranga Hospital in the 1990s when members of the McLeod family kept coming in with stomach cancer.

At least 25 people had died over 30 years because of the disease. They had no idea why.

"I remember there was one young boy who was only 14 years old and he died of the cancer because by the time they got any symptoms, the cancer had spread," Framp said.

Some of the family believed they had had a makutu (curse) placed on them after selling their land several years before for quarrying purposes, and that the cancer was a punishment.

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Finally, some of the afflicted family members met at their marae, Tamapahore, on the outskirts of Papamoa, to discuss what could be done.

"They wanted to find a scientific reason for the cancer being so prevalent among their close relatives," Framp said.

In 1994, family member Maybelle McLeod got funding from the Health Research Council to employ a scientist to search for answers.

She contacted the University of Otago and started working with Professor Parry Guilford, who had an interest in human genetics. He had previously found a mutated gene that caused deafness.

Familial traits for gastric cancer have been recognised for more than 200 years. Evidence shows Napoleon Bonaparte and several members of his family were afflicted with it.

Genetic testing began in the 1950s and could detect the presence of disorders such as Down's syndrome.

But it wasn't until the 1990s that more sophisticated technology was available to discover specific mutations that led to diseases such as breast, ovarian, colon cancer and Huntington's disease.

The McLeod family helped in the scientific process by tracing their whakapapa back to 1915 using libraries, the registry of Births, Deaths and Marriages, hospital records and family members' gravestones.

Members of Walker's family soon after the gene was discovered in 1998: Janine Kakau, Huriana Taite, Maybelle McLeod and (Walker's grandfather) Rangi McLeod. Photo / Herald
Members of Walker's family soon after the gene was discovered in 1998: Janine Kakau, Huriana Taite, Maybelle McLeod and (Walker's grandfather) Rangi McLeod. Photo / Herald

In 1997, Guilford and his team discovered the genetic mutation that was responsible for the stomach cancer – the CDH1 gene.

"Groundbreaking"

It wasn't a surprise to Maybelle McLeod - she knew there had to be a scientific reason everybody kept getting sick - but the discovery meant they could now take action.

"I wasn't shocked that he found it, that's what he was looking for," she told the Herald on Sunday.

Family members could now have a blood test to identify whether they had the gene.

"This was groundbreaking for the family as they now could find out for sure if they were at risk of the cancer," Framp said.

A person with the mutated gene has a 75–80 per cent chance of developing stomach cancer by 80. The average age to develop it is 37.

Walker's family hail from Tamapahore Marea in Papamoa. Photo / Bay of Plenty Times
Walker's family hail from Tamapahore Marea in Papamoa. Photo / Bay of Plenty Times

Women with the gene also have a 39 per cent risk of breast cancer.

The test is carried out as young as 14 because the cancer can develop in the teens.

Once a person discovers they have the gene, they are booked in for a yearly gastroscopy to identify early signs of cancer.

Framp assisted in many gastroscopies on the affected family members.

"At Tauranga Hospital, we would have a morning reserved only for the family so they could have privacy and they could also support one another," she said.

If the cancer has developed, the only treatment is to remove the stomach.

Part of the small bowel is then fashioned to a create a new stomach. The patient can only eat very small portions of food, but over time the newly formed stomach stretches and they can tolerate more.

They lose large amounts of weight, their enjoyment of eating is affected and there are many foods they can no longer tolerate. They can also suffer from side effects such as fatigue, dizziness, diarrhoea and vomiting.

They must have vitamin B12 injections every three months rest of their lives.

Pop star Stan Walker's grandfather, Rangi McLeod, was one of the first in the family to have the blood test. It was discovered he had the faulty gene so he had a gastroscopy and it was confirmed he had stomach cancer.

"This was not a surprise to him as he had already lost so many of his family," Framp said.

McLeod agreed to be the first to have his stomach removed but he died following the surgery after complications.

Some family members have got their stomachs removed as a preventative measure.

"They decided they don't want to risk the cancer after seeing so any family members dying and they have their stomachs out before any signs of the cancer developed," Framp said.

"This is a very difficult decision for the family members as following the surgery, their quality of life is affected."

Research continues

When he found the gene, Guilford was already aware of two other Kiwi families who had seen several members die due to stomach cancer - one in Rotorua and another in Whanganui.

Otago University cancer researcher Professor Parry Guilford, who discovered the gene. Photo / Supplied
Otago University cancer researcher Professor Parry Guilford, who discovered the gene. Photo / Supplied

"Very quickly we were able to go to the other two families and found mutations," he said.

Another 17 families in New Zealand have since been diagnosed with the same gene, thanks to the work of Guilford and the family - 15 Māori, four Caucasian and one Arab family.

Guilford's published research has been built on by doctors worldwide to diagnose other families. He estimates at least 500.

"And it all started in little old Mt Maunganui," Guilford said.

It was also the inspiration for an episode of US medical drama Grey's Anatomy.

In the early years, the patients' initial blood test was sent to Guilford and his team in Dunedin to confirm the gene.

They tested 150 members of Walker's family. Of those, 54 were found to have the gene. Of those, five decided to have preventative surgery, and 19 developed the cancer.

Of the 19, 16 had their stomach's successfully removed after early detection, one person died from complications (Rangi McLeod), one died after checks failed to pick up the cancer early enough and another person dropped off the screening process.

No other family member with the gene has died since, Guilford says.

Blood can now be tested at laboratories in Tauranga so there are likely hundreds more tests carried out over the years.

In total, Guilford's lab carried out 305 blood tests of the 20 New Zealand families until 2010.

In screening for the cancer, Dr David Shaw developed a technique which helped enhance the appearance of tiny lesions. Photo / Bay of Plenty Times
In screening for the cancer, Dr David Shaw developed a technique which helped enhance the appearance of tiny lesions. Photo / Bay of Plenty Times

In 2001, Dr David Shaw, a gastroenterologist at Tauranga Hospital until his death in 2013, found a way to diagnose the cancer at an earlier stage using dye to spray the inside of the stomach during a gastroscopy. It helped enhance the appearance of tiny lesions, turning them white.

"Up until then, you looked and hoped you might see a little lump," Framp said.

However the dye was taken off the market - much to the dismay of doctors. Now,
gastroscopes with magnification can look a bit closer for signs.

In about 2008, Guilford estimates, those affected by the gene became able to avoid passing it on to their children, via IVF.

Cells in the developing embryo can be tested for the mutation. If the embryo is found to have it, it won't be implanted in the mother. But it had ethical implications.

"It's not super-popular in New Zealand," Guilford said.

"Some people feel uncomfortable about making that decision on who to keep and who not to keep ... it gets very complex."

What's next?

Twenty years since the gene was discovered, research is still being done into the family's cancer.

"I have been stuck on this project ever since. It's fascinating," says Guilford, who is still at the University of Otago, in the Department of Biochemistry.

He is excited about the "micro-stomachs" he has been growing in his lab, on which he has been testing various drugs.

He is hoping to start a clinical trial with members of Walker's family within five years.

The end-game is to bring a drug to market that will kill off the cancer and mean they can keep their stomachs.

But the process will take several years.

Guilford also expects patients who have the mutation will eventually be able to have the faulty gene removed and replaced with a normal gene.

Gene therapy studies are being carried out around the world for various diseases but the process was still "a long way off".

Guilford is in contact with the family every couple of weeks and visits them yearly at a health clinic (Kimihauora), which was constructed at their marae in 2001.

It's run by Maybelle McLeod and offers family members support and information about the cancer.

Maybelle McLeod, left, and Aroha McLeod in 2000 on the site of a clinic built at the family's marae to provide support. Photo / Nicola Topping
Maybelle McLeod, left, and Aroha McLeod in 2000 on the site of a clinic built at the family's marae to provide support. Photo / Nicola Topping

Guilford attended the premiere of Walker's documentary last month, in which the singer revealed he had developed the cancer and followed his journey of having his stomach removed.

In it Walker said he often felt like giving up and thanked God every day he was alive.

"I feel like I'm going to suffocate sometimes. I have fevers every night before I go to bed, I wouldn't wish this on anybody," he said.

Walker, pictured soon after his surgery, with Prime Minister Jacinda Ardern, went from 102kg to 67kg. Photo / Instagram
Walker, pictured soon after his surgery, with Prime Minister Jacinda Ardern, went from 102kg to 67kg. Photo / Instagram

Nurse Ann Framp has moved across the ditch and is working as a clinical programme co-ordinator at the University of the Sunshine Coast.

She is now Dr Ann, having completed her PhD on the family's cancer.

Her six-year qualitative study involved interviewing eight family members - from age 18-60 - all of whom had had the gene and their stomachs removed.

"Living with a genetic illness is challenging in many ways. For those with a positive test, they have to decide how they are going to proceed and if they are going to have a yearly gastroscopy and hope they find early signs of the cancer, or make the huge decision to have their stomach removed and live with the side effects for the rest of their lives.

"For those who have a negative test, they can feel guilty they have been spared and they have to witness others in the family making the difficult decisions.

"They have to decide if they will have children who may also be at risk of inheriting the mutated gene. Those who already have children can feel guilty for passing the mutated gene on to them as they are unable to protect them."

Framp travelled back to New Zealand in March and presented her findings to some of the family members at the marae.

"Having the health centre at the local marae where family members work who have an in-depth knowledge of the ramifications of the cancer, and the support they receive from each other, helps them to deal with their affliction."