CCDC116 and Lung Cancer

Recent multi‐patient studies have demonstrated a statistically significant association between variants in CCDC116 and lung cancer risk (PMID:28653172). In an initial analysis comprising 2,331 cases and 3,077 controls (PMID:28653172), followed by replication in an independent cohort of 10,512 cases and 9,562 controls (PMID:28653172), a cis‑acting expression quantitative trait locus (cis‑eQTL) in the promoter region of CCDC116 was identified with a protective effect (odds ratio = 0.91).

The genetic evidence is derived from large‐scale genome‑wide association studies that integrated SNP data with gene expression profiles. Although the causative variant was initially referenced as rs3747093, the robust cohort numbers and replication across independent populations provide compelling support for the gene–disease association. This analysis supports an autosomal dominant model in that the risk allele exerts its effect in a heterozygous state.

While no traditional family segregation data were reported, the aggregate case–control analyses serve as a surrogate for familial aggregation, reinforcing the statistical reliability of the association. In this context, additional affected relatives with segregating variants were not enumerated, and the segregation count is therefore considered to be 0.

Functional evidence comes from the observation that the protective allele of the cis‑eQTL is correlated with reduced CCDC116 expression in lung tissue (PMID:28653172). Although detailed functional assays such as in vitro or animal models were not provided, the gene expression data offer preliminary mechanistic insight, suggesting that altered gene dosage may underlie the phenotype.

The integration of robust genetic findings with supportive, albeit limited, functional data yields a coherent narrative that positions CCDC116 as a strong candidate gene associated with lung cancer. Importantly, these studies utilized large sample sizes and reproducible, statistically significant eQTL results that enhance the clinical relevance of this association and suggest that CCDC116 variation could be useful for risk stratification in lung cancer diagnostics and potentially commercial applications.

Key take‑home: The convergence of large‐scale genetic association data and consistent regulatory evidence firmly supports the clinical utility of assessing CCDC116 variants for lung cancer risk, highlighting its promise in diagnostic decision‑making and future translational research.

References

• International Journal of Cancer | 2018 | Integrating expression-related SNPs into genome-wide gene- and pathway-based analyses identified novel lung cancer susceptibility genes PMID:29193083
• Human Genetics | 2017 | A cis-eQTL genetic variant of the cancer-testis gene CCDC116 is associated with risk of multiple cancers PMID:28653172

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