Cancer Control Research
2R01CA054498-11A1
Breslow, Norman E.
LATE EFFECTS IN WILMS TUMOR SURVIVORS AND OFFSPRING
Abstract
DESCRIPTION (provided by applicant): This proposal is to continue the follow-up
of children and young adults who were successfully treated for Wilms tumor on
protocol studies of the National Wilms Tumor Study Group (NWTSG), as well as
their offspring. With current therapy, 90 percent of children treated for Wilms
tumor will be cured of their disease. However, survivors are at risk for
delayed complications of their disease and treatment that can compromise the
quality and duration of that survival. Therapy for Wilms tumor has changed over
time but still includes surgery, multi-agent chemotherapy, and (for some)
radiation therapy. As children are treated for Wilms tumor in early childhood,
it has taken many years of follow-up to appreciate some of these long- term
effects. For some, we are just beginning to better define these effects 10-20
years post treatment, The mechanisms underlying many of these long
term-complications remain unknown, and thus preventive strategies have yet to
be established. In addition, as we unravel the complex genetic heterogeneity
surrounding the etiology and pathogenesis of Wilms tumor, this may provide
important clues to the mechanisms underling long-term complications. With
respect to late effects, we will determine the incidence, spectrum and
mechanisms of disease, treatment and host-related risk factors for selected
life-threatening chronic toxicities in Wilms tumor patients. These include a)
congestive heart failure b) respiratory failure c) renal failure and d) second
malignant neoplasms (SMN). Related to this, we will determine the incidence and
cause of late mortality in Wilms tumor patients and compare with age and
sex-specific national population rates. Reproductive epidemiology will be
studied with respect to natality, pregnancy outcomes and complications, and
congenital or hereditary diseases in the offspring. By using established family
history data and pedigrees and following offspring of survivors, heritability
and recurrence risks will be estimated and clinical heterogeneity will be
explored. We will collaborate with molecular biologists by facilitating access
to particularly informative subgroups of Wilms tumor patients.
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