Genes Linked to Childhood Cancer Risk
Reported August 24, 2009
(Ivanhoe Newswire) — Scientists have identified inherited variations in two genes that account for 37 percent of childhood acute lymphoblastic leukemia (ALL), the most common childhood cancer.
The study offers the first proof based on a complete survey of the human genome that inheritance plays a role in childhood ALL. Mary Relling, Pharm.D., St. Jude Pharmaceutical Sciences chair and the paper’s senior author, estimated that individuals who inherited variations in genes known as ARID5B or IKZF1 are almost twice as likely to develop ALL as those without the variations. Even then, she said, the risk remains low. ALL strikes roughly one in every 75,000 Americans. Sixty percent are children and teenagers.
“The genetic variations alone are not enough to cause the cancer. Like all cancers, pediatric ALL is a multi-factor disease,” Relling was quoted as saying. “But these findings may give us a handle on the mechanism of the disease and drug responsiveness to it.”
In a study published by the Institute of Cancer Research in Surrey, England, at the same time, exactly the same genes, ARID5B and IKZF1, were confirmed to be altered in British children with ALL.
St. Jude researchers collaborated with colleagues from the Children’s Oncology Group (COG), an international group of medical institutions that cooperate in research studies and clinical trials of childhood cancer treatment.
The new evidence tying inherited variation in IKZF1 to an increased risk of developing ALL underscores the need for medications targeting variations in this gene, Relling said.
Both ARID5B and IKZF1 play important roles in normal development of lymphoid or white blood cells, she said. ARID5B belongs to a family of genes that make transcription factors, which help regulate gene activity. “If they have an inherited variation that affects the function of those genes, these are plausible pathways for how a normal lymphoid cell could be disrupted and transformed into a cancer cell,” Relling said.
Inherited variations in ARID5B might also influence patient response to chemotherapy, particularly to the drug methotrexate. “We found this same inherited variation also affected accumulation of the drug in leukemia cells. It accumulates better. That allows us to use a lower dose and still cure the leukemia,” Relling explained. “These findings may identify a new marker that could be used to help decide on doses of methotrexate in patients with varying ARID5B status.”
SOURCE: Nature Genetics, August 16, 2009
