Pediatric Colorectal Carcinoma is Associated With Excellent Outcome in the Context of Cancer Predisposition Syndromes.

INTRODUCTION: Colorectal carcinoma (CRC) is the second most common adult cancer in Germany, however, it is extremely rare in children and adolescents. In these patients, previous literature describes aggressive behavior and diagnosis at advanced stage. METHOD: Thirty-one patients with CRC age ≤ 18 years and treated between 1990 and 2012 have been identified through the structures and registries of the German Society for Pediatric Oncology and Hematology. RESULTS: The age range was 9-18 years (median 13.5 years); the median follow-up time was 43.9 months (range 1-124 months). Twenty-six patients (84%) were tested for a genetic tumor syndrome (GTS); of these, 11 patients (35% of all patients) tested positive (eight cases of Lynch syndrome, one patient with familial adenomatous polyposis, two patients with constitutional mismatch repair deficiency). An unfavorable histology was reported in 55% of the records (n = 17), a poor differentiation (grade III) in 68% of carcinoma (n = 21). Overall survival (OS) and event-free survival at 5 years was 52.0% and 65.6%, respectively. Five-year survival according to stage was 100% in stage II (n = 2), 100% in stage III (n = 13), and 12.9% in stage IV (n = 15; P < 0.001). Five-year OS in patients with and without a defined GTS was 100% and 36.5% (P = 0.019), respectively. CONCLUSION: Children and adolescents with CRC are frequently diagnosed in advanced stages and have an unfavorable prognosis. In this study, a high percentage of pediatric CRC patients presented with a tumor predisposition syndrome and showed an especially favorable OS.

Rare malignant pediatric tumors registered in the German Childhood Cancer Registry 2001-2010.

BACKGROUND: The German Childhood Cancer Registry (GCCR) annually registers approximately 2,000 children diagnosed with a malignant disease (completeness of registration >95%). While most pediatric cancer patients are diagnosed and treated according to standardized cooperative protocols of the German Society for Pediatric Oncology and Hematology (GPOH), patients with rare tumors are at risk of not being integrated in the network including trials and reference centers. PROCEDURE: A retrospective analysis of all rare extracranial solid tumors reported to the GCCR 2001-2010 (age <18 years) was undertaken using a combination of the International Classification of Childhood Cancer (ICCC-3) and the International Classification of Diseases-Oncology (ICD-O-3). Tumors accounting for <0.3% of all malignancies were defined as rare (approx. 6 cases/year and registered malignancy). RESULTS: According to this definition 1,189 rare extracranial solid tumors (18.2% of all malignant extracranial solid tumors) were registered, among these 232 patients (19.5% of rare tumor cases), were not included in preexisting GPOH studies/registries. Within 10 years, the number of registered non-GPOH-trial patients with a rare tumor increased. CONCLUSIONS: Though most of the GCCR-registered patients with rare malignant tumors are treated within GPOH trials, there is a considerable number of patients that have been diagnosed and treated outside the structures of the GPOH. These patients should be reported to the recently founded German Pediatric Rare Tumor Registry (STEP). Active data accrual and the development of appropriate structures will allow for better registration and improvement of medical care in these patients.

Focused screening of a panel of cancer-related genetic polymorphisms reveals new susceptibility loci for pediatric acute lymphoblastic leukemia.

BACKGROUND: A genetic predisposition to acute lymphoblastic leukemia (ALL) in childhood is well established. Currently known risk loci, however, explain only one third of the estimated total risk related to common genetic variations. PROCEDURE: We genotyped 1,421 polymorphisms in 407 candidate genes from the SNP500Cancer database (National Cancer Institute) using the Illumina Cancer SNP Panel. We investigated 78 cases (aged 0-19 years at diagnosis, and mixed ethnic background) of childhood B-precursor ALL and compared genotype data with those of 1,417 HapMap controls. To account for the ethnic diversity of the study population, structured association by genetically matching cases and controls using identity-by-state similarity was used. Case-control association analyses were performed using Cochran-Mantel-Haenszel tests, adjusted for the population substructure. RESULTS: Common variations rs6966 (3' UTR of PPP1R13L, chr 19q13.32, P = 4.55 × 10(-9)) and rs414580 (intron 2 of MSR1, chr 8p22, P = 6.09 × 10(-8)) were significantly associated with ALL. These SNPs remained significant after adjustment for multiple testing. The SNP rs6966 tags a haplotype block which includes SNPs in PPP1R13L and ERCC2 genes, which are related to DNA repair and cell survival. rs6966 and rs414580 conferred allelic odds ratios of 3.74 (95% confidence interval [CI] 2.31-6.04) and 3.93 (95% CI 2.31-6.69), respectively. CONCLUSIONS: These findings reveal two independent novel susceptibility loci for childhood ALL.