A UC Berkeley-led research group will certainly seek triggers of leukemia — the most common cancer in youngsters — along with a new, four-year, $6 million grant from the Environmental Protection Agency and the National Institute of Environmental Good health Sciences.
(National Cancer Institute photo by Bill Branson)
The award marks the second round of funding for the Berkeley-based Focus for Integrative Research on Childhood Leukemia and the Environment (CIRCLE), directed by Catherine Metayer, a professor of epidemiology along with UC Berkeley’s School of Public Health.
The brand-new grant is one of 5 announced today (July 26) by the EPA for research centers focused on children’s environmental health, and CIRCLE is the only leukemia research Focus funded jointly by the agencies.
The incidence of childhood leukemia in the U.S. has actually increased by about 35 percent due to the fact that 1975, according to Metayer, citing cancer statistics from the National Cancer Institute’s Surveillance, Epidemiology, and End Outcomes Program, and leukemia is one of the leading triggers of childhood death in made countries.
With availability of much more efficient treatments, survival has actually increased dramatically. Survivors, however, face lots of difficulties later in life, including debilitating medical and psychosocial complications, which likewise trigger economic hardships for their families.
“Our target is to identify the triggers of childhood leukemia and to support prevention efforts by educating Good health practitioners, families and public Good health organizations on risk factors for leukemia,” Metayer said.
Focus on acute lymphoblastic leukemia
The grant will certainly enable the scientists to build upon recent victory linking the risk of obtaining childhood leukemia to individual environmental exposures. They will certainly focus their investigations on California’s ethnically diverse population, and on a sort of leukemia called acute lymphoblastic leukemia (ALL). all of accounts for four from 5 cases of childhood leukemia.
Studies indicate that all of in youngsters regularly begins prior to birth, in the mother’s womb, and that exposure of the fetus to cancer-causing chemicals may play a role in initiating the disease.
CIRCLE researchers have actually refined laboratory techniques that much more sensitively detect and quantify chemical exposures in biological samples from newborns and their mothers.
They likewise have actually pioneered analysis of residence dust as an estimate of exposure to chemicals prior to and after birth, and found that dust levels of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and polycyclic aromatic hydrocarbons (PAHs) are associated along with increased risk of childhood ALL.
PCBs are industrial chemicals previously implicated in others cancers. Their production has actually long been prohibited by law in the United States, however PCBs persist in the environment. PAHs are released by the burning of organic substances, ranging from gasoline to meat. PBDEs are flame retardants used in furniture, plastics and foam products.
Metayer, that is chair of the Childhood Leukemia Worldwide Consortium, likewise notes, “Researchers in lots of countries found that exposures to solvents, traffic, pesticides and tobacco smoke are associated along with the risk of making childhood leukemia, while folate supplementation by the mother prior to or throughout pregnancy appears to have actually a protective effect.”
With the brand-new funding, CIRCLE researchers will certainly expand the scope of their research, and investigate means in which chemical and nutrient exposures interact along with genes and the immune system to influence leukemia risk.
“We will certainly be conducting the initial study to characterize a broad range of chemical exposures to the fetus, the initial biomarker study to examine the impact of chemical exposures on the maternal immune status throughout pregnancy and its partnership to childhood all of risk, and the initial study to test suspected chemical sets off of leukemia in a mouse model of childhood ALL,” Metayer said.
Metayer and colleagues have actually led leukemia research collaborations due to the fact that 1995, predating the initial CIRCLE award in 2009. They have actually worked along with clinicians and families to build the California Childhood Leukemia Study along with the most comprehensive exposure data and biospecimen archives worldwide, and recently, they have actually used cancer registries and birth records to identify every childhood leukemia case in California due to the fact that 1988. Along with UC Berkeley scientists, CIRCLE collaborators contain scientists from UC San Francisco, Yale and Stanford universities.
Measuring chemical exposures in newborns
With the brand-new award, CIRCLE researchers will certainly conduct three significant projects. The scientists will certainly be analyzing archived blood specimens from pregnant women and neonatal blood spots from the California Department of Public Good health to measure in utero chemical exposures, to profile aspects of the immune system and to identify genetic alterations that lead to leukemia. They likewise will certainly be testing chemicals in mice and launching brand-new education and outreach efforts related to leukemia prevention.
In the initial project, co-led by Metayer and cancer epidemiologist Xiaomei Ma at Yale, the researchers will certainly explore exactly how the status of the maternal or neonatal immune system is affected by chemical exposures in the womb.
CIRCLE scientists and others researchers in recent years have actually found intriguing associations between the immune system and the progress of childhood leukemia. For instance, youngsters that produce all of tend to have actually much more significant infections throughout the initial year of life, and their mothers likewise are much more most likely to have actually suffered infections while pregnant, Metayer said. In addition, levels of individual immune system signaling molecules might be altered. As portion of this initial project, scientists will certainly measure levels of signaling molecules called cytokines, which are developed primarily by immune cells and suggestions guide immune responses.
The second project will certainly be led by UC Berkeley’s Stephen Rappaport, an expert in research on the “exposome,” which refers to the totality of exposures to an specific from within and from the outside environment over the path of a lifetime. Rappaport optimizes lab protocols for using a technique called mass spectrometry to quantify thousands of chemicals found in blood samples, analogous to the method geneticists now can easily scan the entire genome for mutations. The CIRCLE group could identify brand-new associations between prenatal chemical exposures and childhood leukemia using these refined methods.
The 3rd project, led by CIRCLE co-director Joseph Wiemels, an associate professor of epidemiology and biostatistics at UC San Francisco, focuses on the role of genetic variations that could confer leukemia susceptibility, too as on “epigenetic” modifications, a sort of chemical modification in DNA that might be influenced by chemical exposures. These changes could occur prior to or after birth, can easily be long lasting and influence the functioning of genes.
The brand-new award likewise funds a Community Outreach and Research Translation Core led by Mark Miller of the Western States Pediatric Environmental Good health Specialty Unit at UC San Francisco, along with the try of boosting environmental Good health literacy in various audiences, including Good health care providers and Latinos, and providing a scientific basis for making prevention programs for all of in children.
“The history of environmental Good health is rife along with examples of lessons learned late — chemicals along with early warning signs of Good health impacts that took lots of years or even decades to conclusively prove were hazards,” Miller said. In the meantime their usage continued and they accumulated in the environment. Well-known examples contain PCBs, DDT, lead and tobacco smoke.
“We have actually enough post now,” Metayer said, “to start to explore means in which to reduce children’s exposures that have actually been consistently linked to increased risk for childhood leukemia, and we will certainly go on to seek brand-new risk factors to much better guide future programs for prevention.”
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