Molecular Epidemiology of Childhood Leukemia (Aka The California Childhood Leukemia Study)
Condition: Leukemia; Acute Myelocytic Leukemia; Acute Lymphoblastic Leukemia; Acute Myelogenous Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Observational

Summary: 
      This study is a case-control study investigating the causes of childhood leukemia in Northern
      California. The overall purpose of this epidemiologic study is to find specific genetic or
      environmental factors that may increase the risk of leukemia in children. The study is being
      conducted by Patricia Buffler, PhD at the School of Public Health - University of California
      Berkeley in collaboration with the California Department of Health Services and 16 hospitals
      located throughout the state of California. The study began in 1995 and will continue to
      2014.
    

Detailed 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.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Children diagnosed with leukemia and matched controls
      
Biospecimen description: 
      pre-treatment peripheral blood and bone marrow saliva
    
Keywords: Molecular Epidemiology; Case Control