Description:
<jats:p> 9561 </jats:p><jats:p> Background: Using a unique genealogical resource, the Utah Population Database, we examined risk of cancer in 1st- through 3rd-degree relatives of 4,482 pediatric cancer cases ≤18 years old diagnosed between 1966 and 2009. We quantified cancer risk in relatives of children with cancer in order to determine evidence of a familial aggregation of cancer, identify high-risk pedigrees, and inform counseling protocols for genetic testing and screening. Methods: We estimated cancer risk in relatives of pediatric cases compared to random population controls matched 5:1 on sex, birth year, and birthplace. Odds ratios were calculated using conditional logistic regression, adjusting for number of biological relatives, their degree of relatedness, and their person-years at risk. We included all relatives of cases and controls with followup who linked to a pedigree of ≥2 generations; this approach has been shown to lead to unbiased risk estimates. As observations within families are non-independent, a robust variance estimator for cluster-correlated data was incorporated. Results: Mostly siblings, 1st-degree relatives (N=49 affected) of pediatric cases were at 2-fold increased risk of being diagnosed at age<19 with cancer themselves (p<10<jats:sup>-4</jats:sup>); siblings of cases diagnosed at age<5 had a 4-fold risk of pediatric cancer (p<10<jats:sup>-7</jats:sup>). Likewise, 2nd-degree relatives (N=61 affected) and cousins (N=105 affected) of cases had a ~2-fold risk of childhood cancer (p<10<jats:sup>-4</jats:sup>). Proband siblings were at increased risk for leukemia, brain tumor, epithelial neoplasia, and bone cancer. While 1st-degree relatives of pediatric cases had a slight increased risk of adult-onset cancer, when they do develop cancer they exhibit a 50% increased risk of a Li-Fraumeni Syndrome-related tumor diagnosis (N=142 affected relatives; p<10<jats:sup>-4</jats:sup>). Conclusions: Our findings provide evidence of familial aggregation of cancer and suggest a higher percent of pediatric cancers are related to hereditary syndromes than are adult cancers. We encourage a 3-generation family history be collected and routinely updated for all pediatric cancer patients, and those children with family histories of early-onset cancer be referred for genetic counseling and early surveillance when appropriate. </jats:p>