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Background: Treatment characteristics such as cranial radiation therapy (CRT) do not fully explain adiposity risk in childhood acute lymphoblastic leukemia (ALL) survivors. This study was aimed at characterizing genetic variation related to adult body mass index (BMI) among survivors of childhood ALL. Methods: Genetic associations of BMI among 1458 adult survivors of childhood ALL (median time from diagnosis, 20 years) were analyzed by multiple approaches. A 2‐stage genome‐wide association study in the Childhood Cancer Survivor Study (CCSS) and the St. Jude Lifetime Cohort Study (SJLIFE) was performed. BMI was a highly polygenic trait in the general population. Within the known loci, the BMI percent variance explained was estimated, and additive interactions (chi‐square test) with CRT in the CCSS were evaluated. The role of DNA methylation in CRT interaction was further evaluated in a subsample of ALL survivors. Results: In a meta‐analysis of the CCSS and SJLIFE, 2 novel loci associated with adult BMI among survivors of childhood ALL (LINC00856 rs575792008 and EMR1 rs62123082; PMeta < 5E–8) were identified. It was estimated that the more than 700 known loci explained 6.2% of the variation in adult BMI in childhood ALL survivors. Within the known loci, significant main effects for 23 loci and statistical interactions with CRT at 9 loci (P < 7.0E–5) were further identified. At 2 CRT‐interacting loci, DNA methylation patterns may have differed by age. Conclusions: Adult survivors of childhood ALL have genetic heritability for BMI similar to that observed in the general population. This study provides evidence that treatment with CRT can modify the effect of genetic variants on adult BMI in childhood ALL survivors. Adult survivors of childhood acute lymphoblastic leukemia, particularly those treated with cranial radiation, are at increased risk for obesity. This study provides evidence that the body mass index in adult survivors of childhood acute lymphoblastic leukemia is a genetically heritable trait similar to that in the general population and that the effect of genetic loci from the general population may be modified by treatment with cranial radiation. [ABSTRACT FROM AUTHOR]

Background: In recent years, there has been growing awareness of the distinct characteristics of adolescents and young adults (AYA) diagnosed with cancer. Soft-tissue sarcoma (STS) accounts for approximately 1% of all cancers diagnosed in adults and 8% of cancers diagnosed in AYA. To the best of our knowledge, only a few sarcoma registers include data regarding histological subtype, age at diagnosis, and detailed clinical information. Therefore, little is known regarding clinical presentation and outcomes in AYA diagnosed with STS.Methods: Using the Scandinavian Sarcoma Group Central Register, data were obtained regarding 4977 patients who were diagnosed with STS for the period between 1986 and 2011. AYA (those aged 18-39 years) were compared with older adults (OA; those aged 40-80 years) with respect to clinical presentation, treatment, and outcome.Results: There were 868 AYA and 4109 OA. Overall and by STS subtype, there were significant differences noted between AYA and OA with regard to presentation, treatment, and survival. The distribution of STS subtypes was different between OA and AYA (eg, OA were more likely to be diagnosed with malignant fibrous histiocytoma compared with AYA [34% vs 16%; P < .001]). OA also were more likely to have tumors measuring ≥5 cm (68% vs 56%; P < .001) and a higher malignancy grade (75% vs 67%; P < .001). In the majority of STS subtypes AYA had significantly better overall survival and less disease recurrence compared with OA, but this finding was not true for those with malignant peripheral nerve sheath tumors.Conclusions: There are several differences between AYA and OA with STS with regard to presentation, treatment, and survival, and such differences must be taken into consideration when designing clinical trials. Additional work also is needed to characterize the potential biological mechanisms underlying these differences. [ABSTRACT FROM AUTHOR]

Background: Curative therapy places childhood cancer survivors at increased risk for second primary malignancies (SPMs). However, there have been few population-based attempts to characterize differences between outcomes of SPMs in childhood cancer survivors and outcomes of first primary malignancies (FPMs).Methods: Clinical and demographic information about childhood cancer survivors who developed SPMs and individuals with comparable FPMs was extracted from the Surveillance, Epidemiology, and End Results program. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models comparing the overall survival (OS) of individuals with and without a history of childhood cancer. OS was evaluated both overall and for specific cancers diagnosed in 50 or more childhood cancer survivors. Models accounted for potential confounders, including sex, race, age, treatment decade, histology, and disease stage.Results: Compared with individuals with FPMs (n = 1,332,203), childhood cancer survivors (n = 1409) with an SPM experienced poorer OS (HR, 1.86; 95% CI, 1.72-2.02) after the study had accounted for cancer type, age, sex, race, and decade of diagnosis. A history of childhood cancer remained a poor prognostic factor for all specific cancers evaluated, including breast cancer (HR, 2.07; 95% CI, 1.63-2.62), thyroid cancer (HR, 3.59; 95% CI, 2.08-6.19), acute myeloid leukemia (HR, 2.38; 95% CI, 1.87-3.05), brain cancer (HR, 2.09; 95% CI, 1.72-2.55), melanoma (HR, 2.57; 95% CI, 1.55-4.27), bone cancer (HR, 1.88; 95% CI, 1.37-2.57), and soft-tissue sarcoma (HR, 2.44; 95% CI, 1.78-3.33).Conclusions: Compared with individuals without a prior cancer diagnosis, survivors of childhood cancer with an SPM experienced inferior outcomes. Survival disparities were observed for the most frequent SPMs diagnosed in childhood cancer survivors. [ABSTRACT FROM AUTHOR]