BPIFA1 – Nasopharyngeal Carcinoma Susceptibility

BPIFA1 (also known as SPLUNC1) has emerged as a gene of interest in the susceptibility to nasopharyngeal carcinoma, a disease with a high incidence in Asian populations (PMID:22213098, PMID:28881764). Multiple independent studies have evaluated both the genetic association and the functional impact of BPIFA1 variants, thereby enhancing our understanding of its role in tumorigenesis.

Genetic evidence comes from case‐control studies performed in Malaysian Chinese cohorts. The initial screening with 81 NPC patients (PMID:22213098) and a subsequent replication study with 366 NPC patients (PMID:22213098) provided a combined analysis that demonstrated a significant association, with a reported SNP (rs2752903) and further fine mapping highlighting rs1407019 in an intronic enhancer region. In addition, a meta‐analysis confirmed these findings in an expanded patient population (PMID:28881764).

In the context of genetic evidence, one recurrent variant of interest in BPIFA1 is a promoter polymorphism formatted as a HGVS string: c.1888C>T (p.=). This variant, although located in the non‐coding promoter region, has been shown to modulate gene expression and correlates with altered NPC risk (PMID:33722345). The genetic data thus reflect a strong case–control association with consistent findings across multiple cohorts.

Experimental assessments further support the role of BPIFA1 in NPC susceptibility. In vitro studies have demonstrated that BPIFA1 is expressed as multiple isoforms in human nasal lavage fluid and that these isoforms display LPS‐binding activity, suggesting a role in the innate immune response of the upper airways (PMID:15158712). Complementary functional studies examining the promoter polymorphism have provided evidence of allele‐dependent differences in transcriptional activity, further reinforcing the molecular mechanism by which BPIFA1 influences NPC risk (PMID:33722345).

The integration of robust genetic association and functional experimental data supports a role for BPIFA1 in nasopharyngeal carcinoma susceptibility. While the genetic studies highlight significant associations across a large number of cases (PMID:22213098, PMID:28881764), the functional assays provide a mechanistic basis by demonstrating that the promoter variant leads to altered gene expression. No significant contradictory studies have been reported, underscoring the consistency of the association.

Key take‑home sentence: BPIFA1 is a promising genetic marker with both diagnostic and functional relevance for the risk stratification of nasopharyngeal carcinoma.

References

• Molecular carcinogenesis • 2012 • Identification of a functional variant in SPLUNC1 associated with nasopharyngeal carcinoma susceptibility among Malaysian Chinese PMID:22213098
• Oncotarget • 2017 • Detection of nasopharyngeal carcinoma susceptibility with single nucleotide polymorphism analysis using next-generation sequencing technology PMID:28881764
• Biochimica et biophysica acta • 2004 • PLUNC in human nasal lavage fluid: multiple isoforms that bind to lipopolysaccharide PMID:15158712
• The American journal of the medical sciences • 2021 • Functional Study of Polymorphism 1888 C>T in the Promoter Region of Human PLUNC Gene PMID:33722345

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