Meta-analysis links CD40 rs1883832 polymorphism to breast cancer susceptibility

Photo by Ashraful Islam / Unsplash

Frontiers in Medicine Published May 21, 2026 Medically reviewed May 21, 2026 DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Interpret cautiously: CD40 rs1883832 may influence breast cancer risk, but other polymorphisms show no significant association.

This meta-analysis, based on 10 studies (20 case-control studies), investigated the association between CD40 gene polymorphisms (rs1883832, rs4810485, rs1800686, rs3765459) and cancer susceptibility, with a focus on breast cancer. The primary outcome was the association between these polymorphisms and overall cancer risk, with secondary outcomes including differential CD40 expression between tumor and normal tissues, impact on overall survival, and distribution of mutant alleles across populations.

The main finding was that the rs1883832 polymorphism had a significant impact on breast cancer susceptibility, although specific effect sizes, confidence intervals, and p-values were not reported. In contrast, the other three polymorphisms (rs4810485, rs1800686, rs3765459) showed no significant correlation with tumor susceptibility. The analysis also explored CD40 expression patterns and protein-protein interaction networks, but quantitative results for these secondary outcomes were not provided.

The authors acknowledged several limitations: the study did not explore the potential application of CD40 in early diagnosis of breast cancer, did not clarify its impact on patient prognosis, and did not assess its feasibility as a biomarker. These gaps limit the direct clinical applicability of the findings.

Given the associative nature of the evidence and the lack of reported effect sizes, clinicians should interpret these results cautiously. The findings suggest a potential genetic link that warrants further investigation but do not support immediate changes in clinical practice.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

BackgroundCD40, a constituent of the tumor necrosis factor (TNF) receptor superfamily, exhibits variable expression across different cancer types. It plays a role in mediating tumor cell proliferation, apoptosis, and survival, as well as antitumor immune responses and the tumor microenvironment. Although some studies have suggested a potential association between CD40 gene polymorphisms and cancer risk, definitive conclusions remain elusive.MethodsWe conducted a comprehensive literature search across PubMed, Web of Science, Google Scholar, Embase, and relevant Chinese databases for studies published up to 3 February 2025. Our systematic analysis focused on elucidating the association between CD40 polymorphisms and cancer susceptibility, employing various comparative models and subgroup analyses. We analyzed the differential expression of CD40 between various tumor tissues and their corresponding normal tissues, as well as the impact of CD40 expression levels on the overall survival outcomes of cancer patients using the Gene Expression Profiling Interactive Analysis (GEPIA) database. Based on the NCBI database, we further investigated the distribution characteristics of the mutant allele for four single nucleotide polymorphisms (SNPs) in the CD40 gene across six major global populations. Additionally, we constructed a protein–protein interaction network for CD40 using the STRING database.ResultsBy analyzing 10 high-quality studies (comprising 20 case–control studies), we illustrate that the specific CD40 gene polymorphism (rs1883832) has a significant impact on breast cancer susceptibility. However, no significant correlation was found between the other three CD40 polymorphisms (rs4810485, rs1800686, and rs3765459) and tumor susceptibility.ConclusionOur study found a strong association between CD40 polymorphisms (rs1883832) and breast cancer risk. However, a limitation of this study is that it did not explore the potential application of CD40 in the early diagnosis of breast cancer, nor did it clarify its impact on patient prognosis or its feasibility as a biomarker. These critical issues will be key directions for future research.