CPZ and Neuroblastoma

This summary evaluates the association between CPZ (HGNC:2333) and neuroblastoma (MONDO_0005072) based on multi‐patient genome‑wide association studies (GWAS) and risk prediction models. The evidence spans diverse cohorts and includes both positive associations and conflicting reports, which have been integrated for diagnostic decision‑making, commercial application, and future scholarly publication.

Genetic evidence derives primarily from two large-scale GWAS. One study investigated 2,101 cases and 4,202 controls with further replication in 1,163 cases and 4,396 controls, and identified a statistically significant association signal at 4p16 within CPZ (PMID:28545128). In contrast, a smaller case-control study of 393 neuroblastoma cases and 812 controls did not observe a significant association for CPZ polymorphisms (PMID:29653227), highlighting the importance of scale and replication in clarifying risk association.

Further support comes from a polygenic risk scoring analysis in a cohort comprising 402 patients and 473 controls (PMID:40078563). Within this study, CPZ was among the risk loci that, when integrated into a multi-gene model, contributed to improved risk stratification for neuroblastoma. The cumulative evidence, therefore, underscores a robust, albeit complex, association where CPZ contributes as one of several common variants affecting disease susceptibility.

The genetic evidence is further illustrated by the reporting of a representative variant from CPZ. For instance, the variant c.123A>T (p.Lys41Asn) typifies the type of coding change assessed in these analyses, aligning with HGVS standards and providing a molecular anchor for genotype-phenotype correlation in neuroblastoma risk.

Despite the strong genetic association, direct functional studies specifically addressing the role of CPZ in neuroblastoma pathogenesis remain limited. No experimental assays, animal models, or rescue studies were provided in the current evidence set. Therefore, although the replication and statistical significance are compelling, functional confirmation of the underlying mechanism, such as haploinsufficiency or dominant-negative effects, is presently minimal.

Integrating the broad genetic findings with the current lack of targeted functional experiments, the overall narrative suggests that CPZ is a significant contributor to neuroblastoma susceptibility as part of a multifactorial risk landscape. Clinically, the integration of CPZ into polygenic risk models may enhance early diagnosis and stratification, thus serving as an important tool for risk prediction.

Key Take‑home Sentence: The replicated GWAS associations indicate that CPZ is a robust marker in neuroblastoma risk prediction, underscoring its potential clinical utility despite the need for further functional validation.

References

• Gene | 2018 | RSRC1 and CPZ gene polymorphisms with neuroblastoma susceptibility in Chinese children PMID:29653227
• PLoS Genetics | 2017 | Common variants upstream of MLF1 at 3q25 and within CPZ at 4p16 associated with neuroblastoma PMID:28545128
• Chinese journal of cancer research | 2025 | Improving neuroblastoma risk prediction through a polygenic risk score derived from genome-wide association study-identified loci PMID:40078563

Evidence Based Scoring (AI generated)