Doctors Find ‘Crystal Ball for Childhood Cancer’ in Gene Study

As a doctor who treats young children affected by cancer, Dr. James Downing always gets asked the same question by distraught parents. “Every parent asks me why their child came down with cancer,” the president and CEO of St. Jude Children’s Research Hospital says. “I used to say by and large it was just bad luck. There are a lot of cells dividing, whether in utero, during early development or even puberty. Mistakes can occur, and you get cancer. It’s rare, but it’s bad luck.”

Now he knows that may not be entirely true. In a paper published in the New England Journal of Medicine Wednesday, Downing and his colleagues report that there are a surprising number of genes that can predispose children to developing cancer, before they take their first breath. Such mutations in the cells they inherit from their mothers and fathers, called germ line mutations, can contribute to cancer even in families where there isn’t a strong family history of tumors.

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Downing and his group began with the 565 genes identified by genetics experts as being implicated in cancer, and focused in on 60 genes that can cause cancer if a child inherits one mutated copy from one parent. They compared aberrations in these 60 genes among a group of 1,120 people who had childhood cancers and two other groups, one made up of healthy adults and another of people with autism, who were not diagnosed with cancer and served as controls.

About 8.5% of the people with childhood cancers showed germ line genetic mutations, or genetic changes that they inherited from their parents and put them at higher risk of getting tumors. The cancers that affected these people ranged from solid tumors affecting the brain and bone to leukemia and central nervous system malignancies. By comparison, only 1.1% of the people in the groups not affected by cancer possessed these mutations.

“This is like a crystal ball for childhood cancer,” says Downing. The fact that only 40% of the children with these mutations had a family history of cancer shows that asking about family members with the disease may not be enough to assess whether a child is at risk of getting cancer. In perhaps 60% of cases, it’s possible that family history would not reveal any increased risk of childhood cancer.

Downing admits that at the moment, “the crystal ball is pretty cloudy.” For some of the genes, there is strong scientific evidence that inheriting a mutated copy can lead to certain kinds of cancer. For others, it’s less clear. “We know cancer occurs but we don’t have accurate estimates of the risk of cancer actually occurring,” he says. “We know the risk is high enough that we want to do more frequent screening and follow them. But we just don’t know how high that risk is.”

The results are only the first step in what may ultimately become a standard way of screening children at birth. In the not too distant future, many experts anticipate that people’s genome sequences will be part of their medical records, a vital sign on par with their blood pressure, height and weight. Identifying genes that may predispose people to cancer might be a useful way of determining who needs more intensive screening and treatment and who might not be at elevated risk and can get screened less often.

It’s also likely to change how children who are diagnosed with cancer are treated. “Knowing that a child has a mutation may change the way we treat that patient — the kind of chemotherapy we give, the kind of surgical approach we use, or the kind of radiation treatment that’s given,” says Downing. In coming years, as the understanding of what these mutations mean and how they affect treatment becomes clearer, this information could change the care for patients diagnosed with cancer, and even help them to prevent it from developing in the first place.

Before that can happen, however, Downing says that interpreting and understanding such genetic information, especially figuring out which mutations may or may not predict cancer, will require extensive and good quality counseling about how genes work and the reality that our ability to apply what we learn about our genomes is still in the early stages.