Scientists at the Children's Research Hospital St. Jude identified genetic variations in four genes that are associated with an increased risk of acute lymphoblastic leukemia (ALL) in children of Hispanic origin. The study appears today in the journal Blood.
Genome is the ERG, a transcription factor, which is also mutated in leukemia cells of some patients with ALL. In this study, the researchers identified a heritable genetic variation in ERG, which contribute to all of the risks, especially among Hispanic children. This germline variants, carried in cells throughout the body, rather than the previously reported somatic mutations in cancer cells.
ALL is the most common childhood cancer in children and Hispanics, the highest incidence. They are also less likely than other children to survive.
"The better we understand the biology underlying these differences, the more we have a chance to develop more effective treatments for different groups of patients and more effective methods for tracking and monitoring the risk of disease," - said the corresponding author June D. Young, Ph.D. , an associate member of the Program of hematologic malignancies at the University of St. Jude's cancer and the Department of pharmaceutical Sciences.
Pedigree and risks
This study was conducted in collaboration with the Children's Oncology Group and one of the largest research focused on Latin American patients with ALL. Yang and his colleagues compared the common genetic variation in 940 genetically defined patients with ALL Hispanics registered in the clinical trials, and 681 people with the same origin without a diagnosis of ALL.
Ethnicity was determined on the basis of genetic variation representative of the European, African and Indian descent. Latin American ethnicity was defined as the presence of more than 10 percentage variations of the genes of Native Americans, as well as the presence of a larger number of variations of the genes of the Native Americans than African.
The researchers confirmed previous findings that genetic variation in the high-risk ARID5B, GATA3 and PIP4K2A more common in children of Hispanic origin and associated with an increased chance of developing ALL. The researchers also identified the high-risk variation in ERG, which have been associated with an increased risk of ALL 1.56 times the children of Hispanic origin. According to Yang said, the individual risk is still low.
The risk was highest (twice) for the children with the highest percentage of Native American ancestry, and the lowest (13 percent) for children with the lowest percentage. It was amazing, Young said, because researchers have discovered genes of leukemia showed that their influence on the genetic risk is generally the same for different ancestors.
In contrast, the researchers found no significant increased risk of ALL in African-American children with variations ERG high risk and only 12% increased risk in children of European origin.
"We found that variants of ERG at high risk are more common in Latin American children, but also have a stronger impact on Latinos," - Young said. More research is needed to understand the mechanism, including the possible unidentified environmental or other factors that may play a role.
ERG and risks
The findings also suggest that ERG is an important regulator of normal blood development as somatic mutations or variations in the germ line, which disrupt the function of genes that are currently involved in the development of leukemia. Patients with ALL of Hispanic origin in this study rarely had both germline and somatic variations ERG. Variations themselves are not overlap.