Environmental and Molecular Epidemiology of Childhood Leukemia

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Investigator: Mignon Loh, MD
Sponsor: University of California Berkeley

Location(s): United States

Description

This study is a case-control study of incident childhood leukemia (all subtypes) diagnosed since mid-1995. Children newly diagnosed with leukemia are enrolled in the study. Criteria for inclusion in the study are: under 15 years of age, no prior cancer diagnosis, residency in the state of California at the time of diagnosis, and availability of an English or Spanish speaking parent or guardian. Pre-treatment biological specimens, including bone marrow and peripheral blood, are obtained for analysis in the UCB lab of Dr M. Smith. The lab will use Fluorescence In Situ Hybridization (FISH) to detect chromosome specific aneuploidy and translocations. A number of chromosomal translocations, including t(9;22) and t(8;21), are known to be centrally involved in the development of childhood leukemia. Molecular characterization of the cases with translocations may provide insight into the timing of critical exposures and the nature of the etiological agent involved.

One comparison subject (control) is recruited for each consenting case. For each case, four potential controls are randomly selected from California birth certificate files and matched on date of birth, gender, mother's race, parental Hispanicity, and county of residence. One of the four birth certificate controls is randomly selected to be recruited to participate in the study.

An in-depth personal interview asks a variety of questions, including: residential history; occupational and household exposure histories; mothers' reproductive history; events during index pregnancy and delivery; family history of illness; child's health and vaccination history, contact with other children; maternal and child exposure to cigarette smoke during pregnancy and since birth; maternal and child history of x-rays.

Saliva specimens are obtained from both cases and controls and their biological mothers. The saliva samples are sent to the study office and processed in the Genetic Epidemiology lab at UC Berkeley. DNA from cases and controls will be analyzed by polymerase chain reaction for genetic polymorphisms. Genetic polymorphisms will be examined in two glutathione transferase genes, M1 and Tl. Case samples of peripheral blood, bone marrow, and archived newborn blood will be also used to detect N-ras mutation.

Three tiers of an exposure assessment are being implemented. Tier 1 enrolls and interviews cases and controls seeking to identify risk factors, including residential and occupational chemical exposures. In Tier 2, cases and birth certificate controls that have not changed residence based on specific criteria are part of a reliability study, which seeks to determine if self-reported chemicals used at the time of interview are found in the home during a visual survey several months after interview. Tier 3 aims to document the potential for household exposures by sampling dust on the floor surfaces. The objective is to identify if there are differences in concentrations of pesticides, metals, polyaromatic hydrocarbons, cotinine, polychorinated biphenyls, and ethylenethiourea in the homes of cases and controls. Further, a case-case analysis will identify if cases with chromosomal translocations of interest live in homes with higher concentrations of target compounds than cases that do not have such translocations. These analyses will determine whether leukemic children with common genetic changes experience common exposures and whether these genetic changes have approximately the same temporal occurrence. Finally, we will evaluate whether children with and without leukemia differ with respect to susceptibility.