Family history of cardiovascular disease and cardiovascular comorbidities risk in a pediatric cancer population.

Abstract

10518 Background: Survival rates for childhood cancer patients have improved dramatically, but the growing survivor population suffers from increased treatment-related toxicity including high risk for cardiovascular disease (CVD). While the link between chemotherapy and radiation to cardiotoxicity is well established, few studies seek to determine if an underlying familial risk for cardiovascular disease contributes or predicts this risk. The Utah Population Database (UPDB) is a genealogical resource linked to statewide cancer diagnoses and electronic medical data in which family history is objectively determined. Methods: We calculated the risk of subsequent CVD (ICD-9 401-449) in relatives of 5602 pediatric cancer patients diagnosed at ages 0-19 in Utah from 1966-2013 with no congenital CVD-related anomalies (ICD-9 745-747, 758-759). We identified 964 patients with subsequent CVD diagnoses. Cox models provided recurrence-risk estimates in first-degree relatives of patients compared to relatives of 5:1 matched controls. Results: Pediatric cancer patients were at 5-fold risk of CVD compared to controls ( P< 10-15). In pediatric patients with subsequent CVD, first-degree relatives were at 30% increased CVD risk compared to relatives of cancer-free controls (HR = 1.31, 95%CI 1.16-1.47; P< 10-5). In pediatric patients without CVD, only parents exhibited slight CVD risk (HR = 1.08, 95%CI 1.03-1.14; P= 0.002). In 685,000 individuals with a non-congenital CVD history, pediatric cancers among their first-degree relatives were associated with a similar increased risk of subsequent CVD, compared to pediatric cancers among relatives of controls with no CVD events (HR = 1.39, 95%CI 1.18-1.64, P< 10-4). Conclusions: The UPDB is powerful for investigating comorbidities in cancer patients and their families without recall bias from self-reported family medical history. A family history of CVD may increase risk of CVD-related comorbidities among pediatric cancer patients by 30-40% beyond that observed in patients without a CVD family history. This finding suggests that in addition to a cancer family history, a CVD-related family history should be assessed in children diagnosed with cancer.