|
|
| |
Childhood
Cancer Research Core |
| |
| Highlights
of Research Accoomplishments |
| |
Exposure Assessment |
Exposure assessment
is particularly problematic for epidemiological
studies of childhood cancer because of the
wide geographic spread of study subjects
and controls. The impracticality of direct
exposure assessment has forced investigators
to refine, as much as possible, the questionnaire
tools at their disposal. Where direct measurement
of environmental exposures have been possible,
studies have been designed to capitalize
on the opportunity. This applies to studies
on EMF exposure (carried out in Los Angeles
county by Dr. John Peters and others, and
nationally by Dr. Linet, in collaboration
with Dr. Robison and Dr. Buckley), radon
exposure (in collaboration with NCI and
NIEHS) and pesticide, PAH, metals and ETS
exposure (through house dust sampling).
The house dust study is particularly important,
in that it required coordination of the
efforts of USC investigators, with the subcontractors
at U. Minnesota (responsible for case-control
ascertainment and interviewing), at the
NCI (responsible for establishment of the
EMF cohort), at Westat (responsible for
sample collection), and at SouthWest Research
Institute and Chester Labnet (responsible
for performing all assays). The end result
was a unique data base that included extensive
interview information and comprehensive
analyses of contaminants of house dust in
550 homes. Five manuscripts are currently
in preparation, reporting the results of
analysis of these data, not only with respect
to the key hypothesis that exposure to one
or more component of house dust might increase
leukemia risk, but also to give new insights
into factors which correlate with high levels
of contamination of the home with any of
the analyzed materials.
|
Genetic susceptibility |
Interest in the role
of genetic susceptibility has grown steadily
over the last five years, and Dr. Van Tornout
has established a very active program in
this area. Current projects include studies
of neuroblastoma, brain tumors, and Ewing’s
sarcoma. Preliminary data indicate that
GST polymorphisms may be associated with
risk of neuroblastoma (GST-P1 null conferring
high risk) and brain tumors (associations
with GST-P1, GST-T1 and MTHFR). R01 applications
are in development for both these tumors
to investigate the role of genetic susceptibility.
For brain tumors, the involvement of MTHFR
raises the intriguing possibility of a gene-environment
interaction between this key enzyme of folate
metabolism and level of folate intake during
pregnancy. Consultation with the Biostatistics
Core was particularly vital in the design
of this study, since the study needed to
be able to address the potential role of
the case’s genotype, the mother’s
genotype, the case’s exposures and
the mother’s exposures, as well as
interactions. |
In addition, Dr. Buckley has collaborated
on a CCG study that showed clear evidence
of interaction between an environmental exposure
(induction chemotherapy, in AML patients,
given either by standard or intensively timed)
and a metabolic polymorphism (GST-P1) in determining
a patient’s risk of experiencing a lethal
toxicity.
|
Brain tumor
studies |
Dr. Preston-Martin is regarded as a foremost
authority on the etiology of childhood brain
tumors, with interest in this disease going
back almost twenty years. She coordinated
a highly ambitious multi-national case-control
study of brain tumors, including 1218 cases
and 2223 controls at 9 centers, and much of
her energies in recent years have been focused
on a complete and through analysis of the
data from that study. Among the publications
to come from the study have been manuscripts
on maternal consumption of cured meats and
vitamin supplements during pregnancy; exposure
to tobacco smoke; use of electric blankets
and water beds; and head injury. Additional
publications will cover: epilepsy and anticonvulsant
use; residential water source and nitrite/nitrate
content of household water as assessed from
dipstick measurements; medication use by mothers
during the pregnancy and by the children;
birth characteristics (including birthweight,
parental age, birth order and history of birth
defects in the index child or his siblings);
use of rubber baby bottle nipples and pacifiers;
child’s diet and other early exposures.
|
Second malignancies |
Of all the late effects
of cancer therapy, perhaps none is so interesting
to the cancer epidemiologist as second malignancy.
Investigation of second cancers can potentially
provide insight into both genetic predisposing
factors (for example, the high risk of osteosarcoma
in children with retinoblastoma, who carry
a constitutional rb mutation) and environmental
carcinogens. Dr. Bhatia has demonstrated
a long-standing interest in understanding
the determinants of risk for a second malignancy,
and was lead author on a key article published
in the NEJM on the alarming incidence of
second cancers, and particularly breast
cancer, in long-term survivors of Hodgkin’s
disease who had received radiation therapy. |
| |
|
|
