Researchers at King's College London and Hiroshima University have identified a specific gene linked to oropharyngeal squamous cell carcinoma through a genetic study of a family with 10 members who have developed the condition, according to research published in the American Journal of Human Genetics.
The study uncovered a mutation in the ATR gene, demonstrating the first evidence of a link between abnormality in this gene and an inherited form of cancer. The researchers say this finding raises new ideas about genetic factors linked to throat cancer and provides a platform for exploring the role of ATR more generally in cancer biology.
The researchers carried out a genome-wide linkage study in a U.S. family with an unusual hereditary condition affecting 24 members of the family over five generations. Characteristics include developmental abnormalities of hair, teeth, and nails, as well as dilated skin blood vessels. Strikingly, nearly every person with the condition involved in the study had developed oropharyngeal squamous cell carcinoma in their 20s or 30s, according to the researchers (AJHG, February 2012, Vol. 90:3, pp. 511-517).
The team took blood samples from 13 members of the family and from 13 unaffected people. After analyzing these samples they found a single mutation in ATR was present in all the people with the condition, but none of the unaffected people had the mutation. Ten of the 13 people with the condition had developed oropharyngeal cancer.
This is the first evidence connecting abnormalities in the ATR gene with susceptibility to this type of cancer, according to John McGrath of the King's College London Genetic Skin Disease Group at St John's Institute of Dermatology.
"We know that ATR encodes a protein critical to the way cells repair their DNA, and is therefore a vital mechanism," he said. "We now plan to investigate the cancer pathways in more detail to try to find new treatments."
