THURSDAY, June 6, 2002 (HealthDayNews) -- Researchers have found a gene with one of the strongest links yet to testicular cancer, the most common tumor in young men.
The gene, hiwi, appears to be significantly overactive in about 63 percent of men with a form of testicular cancer called seminoma, according to a new study by Duke University scientists. It acts as a regulator for other genes and proteins involved in the manufacture of sperm in men and eggs in women.
Intriguingly, the researchers found in a second study that animal evidence also suggests unusually quiet hiwi may be linked to sterility, although this has yet to be demonstrated directly in people.
"It's basically a one-plus-one is more-than-two situation," said Haifan Lin, a Duke cell biologist and co-author of the two studies. "If it's overactive, it leads to cancer. If it's underactive, it leads to infertility."
Testicular cancer occurs in about 1 percent of men. If caught early, up to 95 percent of the cases are curable. However, treatment often requires removing the testes, rendering men infertile.
Understanding the genetics of the disease may one day help prevent it entirely or correct the errors that lead to tumors, thus preserving a man's ability to have children, Lin said.
In the first study, reported in today's issue of the journal Oncogene, Lin's group analyzed testicular cancer cells from 35 men with the disease, 19 of whom had seminomas. The rest had nonseminomas, another form of tumor that can be especially deadly.
The hiwi gene was normal in nonseminoma cells. But in 12 of the 19 men with seminomas, its activity was sharply higher -- between three and 16 times more than normal, Lin said.
Most suspected genes for testicular cancer are involved in about 10 percent of tumors, Lin said. So at more than 60 percent, hiwi seems to be much more of a player.
However, another gene, TGTC1, may increase the risk of testicular cancer 50-fold in the men who carry it. This gene has been narrowed to the X (or female sex) chromosome, but has yet to be identified despite two years of searching.
Joseph Nadeau, an expert in cancer genetics at Case Western Reserve University, said that struggle reflects the difficulty in linking specific genes to testicular tumors. "It shows one of the strongest patterns of inheritance, and yet it seems to be so genetically complex that most cases are sporadic," Nadeau said.
Until the Duke researchers can prove that inheriting hiwi leads to testicular cancer, the gene must be considered merely one of many candidates for susceptibility to the disease, he said.
In the second study, appearing in tomorrow's issue of Developmental Cell, Lin's group found that the mouse version of hiwi, a gene called miwi, marshals the production of sperm in male rodents. The researchers showed that male animals missing miwi had much smaller testicles than their normal cage mates and they produced no sperm.
Miwi belongs to a family of genes known as piwi, which Lin first discovered in fruit flies. These genes help control a wide range of reproductive functions.
The next step, Lin said, is to look for signs of defective or absent hiwi in sterile or infertile men. Lin said he's hopeful that the gene flaw will be present, because it's a consistent feature of reproductive trouble in many animal species and even some plants.
What To Do
For more on testicular cancer, try the The Testicular Cancer Resource Center, the UrologyChannel, or the National Cancer Institute.
For more on infertility, check out the American Society for Reproductive Medicine.
