Though they may be short of stature, people with Laron syndrome — a genetic disorder that causes dwarfism — come up big on health. A new study has found that a population of Ecuadoreans with the disorder might be near-impervious to cancer and diabetes, and scientists hope to find a way to replicate those health benefits in the population at large. Laron syndrome is caused by a mutation to a single DNA molecule in the GHR gene, which regulates growth hormone proteins in the body. The mutation renders the gene defective and results in stunted growth. Several decades ago, researchers noticed that yeast and mice with defective growth hormone receptor genes live much longer and healthier lives than do their typically growing relatives. In the case of yeast, said Valter Longo, a gerontologist at the University of Southern California and one of the current study’s lead authors, dwarf varieties can live up to three times longer than normal yeast.
When Longo heard that his colleague, fellow co-author Jaime Guevara-Aguirre at the Institute of Endocrinology in Quito, Ecuador, was working with a population of people with Laron syndrome who never seemed to get chronically ill, Longo wondered if there could be some connection to dwarf mice’s and yeast’s longevity.
“Lots of people were working with yeast and mice,” Longo said, “but nobody was working on the human population.”
So Longo and his colleagues went to Ecuador to investigate the potential link. They looked at data collected over 22 years from approximately 100 Ecuadoreans with Laron syndrome and compared them with their relatives who grew up and lived in the same conditions.
The researchers found that none of those with Laron syndrome had been diagnosed with diabetes, compared with 5 percent of their relatives, and only one reported any tumorous growth — a woman had a benign ovarian tumor — compared with 17 percent of their relatives. She had the tumor removed and thereon remained cancer-free. The researchers reported their findings this week in the journal Science Translational Medicine.
Why might dwarfism protect against cancer and diabetes? Based on his work with mice and yeast, Longo thinks two different mechanisms might be at work.
A defective growth hormone gene interferes with the body’s ability to process insulin, leading to low insulin levels and lower risk for diabetes. As for cancer, when the researchers looked at tissue cells bathed in blood serum from people with Laron syndrome, the DNA in those cells seemed to be protected against mutations.
Longo said that current growth-hormone blocking medications used to treat acromegaly, a type of gigantism, might one day help prevent cancer or diabetes in people at high risk for those diseases, but much more testing will be needed before that becomes a reality.
“Dr. Longo and his colleagues have definitely placed the [growth hormone/insulin growth factor] axis as a major player in the development and/or progression of human diabetes and cancer,” said Ohio State University molecular biologist John Kopchick, who helped pioneer the growth hormone work in mice.
Karen Wernli, an epidemiologist at the Group Health Research Institute in Seattle, said she’d like further studies in this area to calculate what the expected rate of cancer in this population is in order to give a more accurate picture of what might be being prevented.
“It could be that these results are true,” she said, “or it could be that this population just has a lower rate of cancer in general … due to differences in environment or the way they are treated in their culture.”
dwarfism,dwarf,Laron syndrome,Laron,cancer,diabetes
