WDR4 Gene Variant Linked to Prostate Cancer Risk in Genetic Study

A single-letter change in a gene that helps regulate RNA chemical modifications may influence a person’s susceptibility to prostate cancer, according to a study published in the journal Frontiers in Genetics. Researchers from Huaian First People’s Hospital and Nanjing Medical University report that a genetic variant known as rs8130270, located within the WDR4 gene, showed a statistically significant association with prostate cancer risk in both a discovery and an independent validation population. The m7G pathway has previously been implicated in tumor development and in immune responses, but whether inherited variants in m7G-related genes contribute to prostate cancer risk had not been systematically clarified.

The research team set out to address that gap by combining gene expression analysis, genetic association testing, and single-cell transcriptomics. The investigators began by carrying out differential expression analysis on mRNA levels to identify m7G-related genes that might be relevant to prostate cancer risk. Once candidate genes were identified, they turned to logistic regression, a statistical method commonly used in genetic association studies, to examine whether common polymorphisms in those genes were linked to the likelihood of developing prostate cancer.

Crucially, the researchers applied this approach in two stages: a discovery stage to detect initial signals, and a validation stage in an independent population to confirm that the associations were not statistical flukes. In the discovery stage, the variant was associated with prostate cancer risk with an odds ratio of 0.89, a 95 percent confidence interval of 0.82 to 0.96, and a false discovery rate-adjusted P value of 2.65 times 10 to the power of minus 2. An odds ratio below 1 in this context indicates that the variant was less common among prostate cancer cases than among controls, suggesting a protective association rather than a risk-increasing one.

The confidence interval, which does not cross 1, indicates that the association reached conventional statistical significance after correction for multiple testing. Importantly, the association held up in an independent population, where the variant again showed a significant relationship with prostate cancer susceptibility, with an odds ratio of 0.98, a 95 percent confidence interval of 0.97 to 1.00, and a P value of 4.16 times 10 to the power of minus 2. The direction of the effect was consistent across both stages, although the magnitude of the odds ratio differed between the two populations, a pattern that underscores the value of replication in separate cohorts.

To probe the mechanism behind the association, the researchers examined whether rs8130270 acts as an expression quantitative trait locus, or eQTL. In prostate tissue, such an eQTL effect was indeed observed between rs8130270 and WDR4, suggesting that the variant may influence prostate cancer susceptibility by regulating how much WDR4 is expressed. The authors note that this points to a potential regulatory relevance of the variant to WDR4 expression, although the precise functional pathway linking the variant to cancer biology remains to be fully worked out.

The study also found that WDR4 expression is significantly higher in prostate cancer tissues than in normal prostate tissue. When the researchers examined clinical outcomes, they observed that prostate cancer patients with high WDR4 mRNA levels had worse overall survival, with a hazard ratio of 1.67 and a 95 percent confidence interval of 1.06 to 2.64, corresponding to a P value of 2.00 times 10 to the power of minus 2. A hazard ratio above 1 indicates that higher expression was associated with a greater risk of death during the follow-up period.

This survival analysis is observational in nature, and the association between expression and survival does not by itself prove that WDR4 drives tumor progression, but it is consistent with the idea that the gene plays a meaningful role in the disease. One of the more distinctive aspects of the study is its use of single-cell transcriptome sequencing data to map where WDR4 is active within the tumor immune microenvironment. The analysis showed that the WDR4 gene was expressed across various immune cell subsets, and that at the single-cell level, WDR4 expression levels differed between normal and metastatic tissues.

Because the m7G pathway is known to affect immune responses, this pattern of expression across immune cells raises the possibility that WDR4 could influence how prostate tumors interact with the immune system, although the study did not establish a causal role for the gene in immune regulation. Taken together, the findings suggest that rs8130270 in WDR4 is associated with prostate cancer susceptibility and may have regulatory relevance to WDR4 expression. The authors caution that their claims are their own and do not necessarily represent those of their affiliated organizations or the publisher.

Subject of Research: Association of genetic variants in the m7G-related gene WDR4 with prostate cancer susceptibility

Article Title: Genetic variants in WDR4 influencing m7G modification are associated with prostate cancer susceptibility

Article References: Jiang, H., Diao, S., Zhao, J., & Liu, X. (2026). Genetic variants in WDR4 influencing m7G modification are associated with prostate cancer susceptibility. Frontiers in Genetics, 17, 1867208. https://doi.org/10.3389/fgene.2026.1867208

Image Credits: AI Generated

DOI: 10.3389/fgene.2026.1867208

Keywords: prostate cancer, WDR4, m7G modification, genetic variants, rs8130270, eQTL, single-cell transcriptomics, cancer genetics, RNA modification, overall survival, immune microenvironment, logistic regression