Testicular cancer. In this coloured transmission electron micrograph of a section through teratoma cancer cells in a testis, three rapidly dividing cancer cells are seen at centre left and right, and lower right. They have large, irregular nuclei (pale brown) and green cytoplasm
Several serious conditions of childhood may be the result of testicular tumours affecting older fathers, an Oxford University study suggests. Previous research has suggested that some disorders are the result of mutations accumulating with age in sperm-producing cells. However, this would not account for the degree to which the prevalence of some diseases increases in line with the father's age at conception.
Researchers led by Professor Andrew Wilkie of the Weatherall Institute of Molecular Medicine at Oxford University examined the impact of small testicular tumours. They found that these tumours encourage cells to divide and multiply and to produce more germ cells with mutations. The number of sperm carrying mutations therefore increases as men age. The findings may help to explain why, despite screening thousands of genes, scientists are unable to account for the genetic element of many diseases.
Professor Wilkie believes most men develop these tiny clumps of mutant cells in their testicles as they age. 'They are rather like moles in the skin, usually harmless in themselves,' he said. 'But by being located in the testicle, they also make sperm, causing children to be born with a variety of serious conditions.'
The researchers identified two genes affected by this process. These genes are associated with disorders linked to stillbirth, as well as Apert, Noonan and Costello syndromes and a number of other conditions. Future research would need to look for other genes affected, the researchers said.
Goriely A, Hansen RMS, Taylor IB et al. Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for congenital disorders and testicular tumors. Nature Genetics 2009; 41: 1247-52