Molecular Epidemiology of Childhood Leukemia (Aka The California Childhood Leukemia Study)

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.

Cases must be children ages 0-14 newly diagnosed with leukemia (any type) at one of
participating hospitals. They must live in the state of California at diagnosis, never
have been diagnosed with a prior cancer and have a parent or guardian that speaks English
or Spanish.

Controls are matched on the case child's DOB, gender, mother's race, parent's Hispanicity.
In order to be eligible, they must have no history of cancer, have a parent or guardian
that speaks English or Spanish and they must live in the state of California.