Dataset Information

CASP8 SNP D302H (rs1045485) is associated with worse survival in MYCN-amplified neuroblastoma patients.

ABSTRACT:

Background

Neuroblastoma is a pediatric cancer that exhibits a wide clinical spectrum ranging from spontaneous regression in low-risk patients to fatal disease in high-risk patients. The identification of single nucleotide polymorphisms (SNPs) may help explain the heterogeneity of neuroblastoma and assist in identifying patients at higher risk for poor survival. SNPs in the TP53 pathway are of special importance, as several studies have reported associations between TP53 pathway SNPs and cancer. Of note, less than 2% of neuroblastoma tumors have a TP53 mutation at diagnosis.

Patients and methods

We selected 21 of the most frequently studied SNPs in the TP53 pathway and evaluated their association with outcome in 500 neuroblastoma patients using TaqMan allelic discrimination assays.

Results and conclusion

We investigated the impact of 21 SNPs on overall survival, event-free survival, age at diagnosis, MYCN status, and stage of the disease in 500 neuroblastoma patients. A missense SNP in exon 10 of the CASP8 gene SNP D302H was associated with worse overall and event-free survival in patients with MYCN-amplified neuroblastoma tumors.

SUBMITTER: Rihani A

PROVIDER: S-EPMC4263607 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

CASP8 SNP D302H (rs1045485) is associated with worse survival in MYCN-amplified neuroblastoma patients.

Rihani Ali A De Wilde Bram B Zeka Fjoralba F Laureys Geneviève G Francotte Nadine N Tonini Gian Paolo GP Coco Simona S Versteeg Rogier R Noguera Rosa R Schulte Johannes H JH Eggert Angelika A Stallings Raymond L RL Speleman Frank F Vandesompele Jo J Van Maerken Tom T

PloS one 20141211 12

<h4>Background</h4>Neuroblastoma is a pediatric cancer that exhibits a wide clinical spectrum ranging from spontaneous regression in low-risk patients to fatal disease in high-risk patients. The identification of single nucleotide polymorphisms (SNPs) may help explain the heterogeneity of neuroblastoma and assist in identifying patients at higher risk for poor survival. SNPs in the TP53 pathway are of special importance, as several studies have reported associations between TP53 pathway SNPs and ...[more]

PMID: 25502557

Similar Datasets

Project description:BackgroundNeuroblastoma is the most common pediatric solid tumor. MYCN-amplification is an important negative prognostic indicator and inherited genetic contributions to risk are incompletely understood. Genetic determinants of stature increase risk of several adult and childhood cancers, but have not been studied in neuroblastoma despite elevated neuroblastoma incidence in children with congenital overgrowth syndromes.MethodsWe investigated the association between genetic determinants of height and neuroblastoma risk in 1538 neuroblastoma cases, stratified by MYCN-amplification status, and compared to 3390 European-ancestry controls using polygenic scores for birth length (five variants), childhood height (six variants), and adult height (413 variants). We further examined the UK Biobank to evaluate the association of known neuroblastoma risk loci and stature.ResultsAn increase in the polygenic score for childhood stature, corresponding to a ~0.5 cm increase in pre-pubertal height, was associated with greater risk of MYCN-amplified neuroblastoma (OR = 1.14, P = .047). An increase in the polygenic score for adult stature, corresponding to a ~1.7 cm increase in adult height attainment, was associated with decreased risk of MYCN-amplified neuroblastoma (OR = 0.87, P = .047). These associations persisted in case-case analyses comparing MYCN-amplified to MYCN-unamplified neuroblastoma. No polygenic height scores were associated with MYCN-unamplified neuroblastoma risk. Previously identified genome-wide association study hits for neuroblastoma (N = 10) were significantly enriched for association with both childhood (P = 4.0 × 10-3 ) and adult height (P = 8.9 × 10-3 ) in >250 000 UK Biobank study participants.ConclusionsGenetic propensity to taller childhood height and shorter adult height were associated with MYCN-amplified neuroblastoma risk, suggesting that biological pathways affecting growth trajectories and pubertal timing may contribute to MYCN-amplified neuroblastoma etiology.

Dataset Information

CASP8 SNP D302H (rs1045485) is associated with worse survival in MYCN-amplified neuroblastoma patients.

Background

Patients and methods

Results and conclusion

Publications

CASP8 SNP D302H (rs1045485) is associated with worse survival in MYCN-amplified neuroblastoma patients.

Similar Datasets

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