Scientists have identified two genetic variations that account for 57 percent of cases of thyroid cancer, a finding that could lead to earlier detection among people at high risk for the disease.
The report, from the Icelandic company Decode Genetics, may also lead to a resurgence of interest in the quest for the genetic roots of other common maladies like heart disease and schizophrenia. Genetic variants for many such diseases have been identified, but most have turned out to account for a disappointingly small percentage of cases.
A scientific team led by Julius Gudmundsson of Decode Genetics reported Friday in the journal Nature Genetics that the two variants each lie at a site on the human genome near genes that control development of the thyroid gland. The variants are changes in a single chemical unit of the genome, which is some three billion units in length.
Compared with people who have neither variant, “the risk associated with these variants was almost sixfold, which is quite extraordinary,” said Dr. Erich M. Sturgis, a head and neck surgeon at the M. D. Anderson Cancer Center in Houston who was not connected with the research.
Dr. James A. Fagin, chief of endocrinology at the Memorial Sloan-Kettering Cancer Center in New York, said the new study was a significant advance, noting that the Decode Genetics scientists had bolstered their results by replicating the findings among Icelanders in two other populations of European descent, in Columbus, Ohio, and in Spain.
About 4 percent of people of European descent carry both variants, the scientists reported; they did not have information on other ethnic groups.
There are some 35,000 cases of thyroid cancer in the United States each year, but because of an effective treatment — removing the gland and giving patients replacement thyroid hormone — only about 1,500 people die of the disease. It would probably not be worth screening the whole population for the two new variants, at least not until the cost of genetic tests was substantially reduced.
But the test could be useful in groups at special risk, including families where one member has thyroid cancer, said Dr. Kari Stefansson, chief executive of Decode Genetics.
Dr. Fagin agreed that the ability to give such people more predictability “could be a real advantage.”
The Decode Genetics scientists found that subjects with the two variants had lower levels of thyroid-stimulating hormone in their bloodstream. That hormone, produced by the pituitary gland, directs the thyroid gland to generate its own hormones.
The thyroid-stimulating hormone also makes cells of the thyroid gland mature. Dr. Stefansson said it was conceivable that in people with the double variants the thyroid cells were not properly differentiated, and that the immature cells might be the cause of cancer. If so, supplying extra thyroid-stimulating hormone could make the cells mature and reduce the cancer risk.
Dr. Stefansson and other scientists emphasized that for now, that was just speculation.
Most genetic variants found to be associated with common diseases have turned out to account for just 1 percent or so of cases. Dr. Stefansson said the problem was that the variants had been expected to be common, and the gene chips used to analyze patients’ genomes were designed to look for common variants, not for rare ones. But it is the rare ones, he said, that now seem likely to account for most genetic disease. Evidently, natural selection winnows out disease-causing genes before they get to be common.
Dr. Stefansson said Decode Genetics had developed new and cost-effective methods to search the Icelandic population for rare variants. Those, he said, “will allow us to capture much more of the total genetic risk of common diseases.”
The next question will be to find out - one day, when a test is available - whether this is the case with Mum and I and, potentially, Katelyn.
Do I really want to know? :(