second cancers and 82 had not.
When they scanned each patient's genome, focusing on 665,313 tiny genetic variations known as single nucleotide polymorphisms, they found three variations that appeared far more often in patients with second cancers. When they repeated the study using a different set of patients62 cases with second cancers and 71 withouttwo of the three markers were significant.
Those two markers were both from a small region known as 21q on chromosome 6. Both are positioned near a gene known as PRDM1.
The genetic variations closely associated with increased cancer risk, and with each other, appeared to decrease activation of the PRMD1 gene. They had no detectable effect any other genes. Cells with the protective version of both markers expressed PRDM1 after being exposed to radiation. Cells with the variants linked to subsequent cancers did not produce any PRDM1.
Previous studies have found that PRDM1 is involved in a variety of fundamental cellular processes, including proliferation, differentiation and apoptosiswhich can all go awry in cancer. The gene's activity is lost in many cancer types.
In Onel's small samples, only three percent of patients with both of the protective variants developed second cancers within 30 years; nearly 33 percent of those with both of the high-risk variations did.
"Taken together," the authors note, "our findings support a novel role for PRDM1 as a radiation-responsive tumor suppressor." PRMD1 may be important for understanding the causes of second cancers in survivors of pediatric Hodgkin's lymphoma as well as in other cancer patients treated with radiation therapy."
This study should also "bring some optimism" back to genome-wide association studies, Onel added. Most previous cancer-related markers found through GWAS have been "of little clinical value for predicting risk, response to therapy or survival." But by incorporating environmental exposure, suc
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| Contact: John Easton john.easton@uchospitals.edu 773-702-6241 University of Chicago Medical Center Source:Eurekalert |
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