With an eye for the family tree

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Care of patients with hereditary colon cancer is rapidly developing, largely thanks to the efforts of Professor Annika Lindblom. For 30 years, she has refined the treatment of this disease through her research and achieved a major breakthrough when she found the gene for Lynch syndrome.

Annika Lindblom has paved the way for a whole new approach to treatment of hereditary colon cancer.

"My focus is on reducing the incidence of cancer, especially among young patients and in families with hereditary cancer. That's why my discovery of the gene for Lynch syndrome, which causes colon cancer, was an important breakthrough," says Annika Lindblom, senior physician, Clinical Genetics, Karolinska University Hospital and a professor at Karolinska Institutet.

Since then care for patients at risk for hereditary colon cancer has significantly improved. This group is offered colonoscopy screening to detect cancer as early as possible, as well as preventive surgery, since studies show that colonoscopy and lab diagnostics produce good results. But the journey to reach this point has been long.

"In the 1990s we tried various methods to identify these patients through primary care centers and similar strategies to offer them screening services such as colonoscopy. At that time we were criticized for worrying people unnecessarily and for recommending prophylactic surgery. The belief was that 'you shouldn't surgically remove healthy body parts.' But, that was then; the view now is quite different."

How do you find the hereditary connection?

"If you have an eye for the connections in a pedigree, a family tree, it is quite clear when a disease is hereditary. The correlation is of course easier to see in large families than in small ones. Another common sign of heredity is that people fall ill at an earlier age than usual."

When Annika Lindblom started investigating colon cancer 20 years ago, she soon clearly recognized the hereditary connection. Many families also understood this connection, even without confirmation from the healthcare system, since the disease recurred within the family.

"At the same time, it has been a bit of a pioneering initiative both to bring awareness to other parts of the healthcare system and to promote the benefits of screening. Initially we encountered resistance to our recommendation of regular colonoscopies to be able to detect cancer as early as possible. For example, I remember how one surgeon stood up when I was invited to present a lecture, and exclaimed: 'What a load of crap' But I quickly became immune to such protests, which ultimately diminished over time."

What is the next step in treatment of patient groups with hereditary colon cancer?

"The methods are still a bit unrefined and I hope we can find ways to improve them. The best method today is prophylactic surgery to remove healthy organs at risk, including the breasts, ovaries and colon. In addition, a vaccine for some groups, including for Lynch syndrome, may already be possible, but it is too expensive to produce."

It has also been shown that aspirin may reduce the risk of colon cancer.

"In rare cases, it may be an option to offer aspirin, if patients can tolerate it, but not everyone can. At the same time, we need to keep the doses low because it can cause substantial side effects. More studies are needed in this area to find the appropriate dose."

Annika Lindblom also mentions pre-implantation genetic diagnosis (PGD) as a possibility to select embryos without the trait for hereditary cancer.

"Some families have an extremely traumatic history, with many family members suffering from serious illness at an early age. In such cases PGD may be an option, but that presumes both that the individual has a serious hereditary disease and that there is a known serious underlying mutation."

Facts

About Lynch syndrome

Lynch syndrome increases the risk of colon cancer. In Sweden about 700 people suffer from Lynch syndrome. About 300 people with Lynch syndrome come to Gastrokliniken (Department of Gastrointestinal Diseases) at Karolinska for regular monitoring. The purpose of this screening program is to detect cancer at an early stage so it can be removed.

The group of patients with a different kind of hereditary colon cancer, but where no gene has been identified, is much larger. These patients participate in screening programs at several other hospitals.

Family tree for hereditary colon cancer

The family tree is made up of several generations, including both men and women. The black marks show those who have been diagnosed with cancer – many earlier than usual. Each generation has people who have fallen ill. The tree shows a clear hereditary pathway, as well as how commonly cancer occurs. The family tree, a pedigree, is an important and simple tool both for research and for contact with patients.

Prizewinning clinical research

Annika Lindblom was awarded the 2014 prize for her "Breakthrough in clinical research." The research prize was established by the Stockholm County Council Research Council. The prize was awarded because "Annika Lindblom has focused on explaining hereditary colon cancer for 30 years. By combining first-class molecular research with clinical management, she has essentially eliminated colon cancer as a cause of death in families where half their members previously died from this disease."

The expert group that assessed her work describes a clinically relevant research line consistently implemented over a long period. The pieces of the puzzle have fallen into place one by one, resulting in outstanding clinical relevance.

"It feels great for several reasons. The award shifts the focus to the patients. Research shows that it is important to detect hereditary cancer early and to offer prevention and counseling. The results have meant a lot to affected families. And of course it's great to be recognized for all the work that lies behind the results," says Annika Lindblom.