Abstract
Background Recently, unexpected autoimmune regulator (AIRE) implication in the scenario of several cancers, including breast cancer (BC), has emerged. This study aims to explore for the first time the possible association between AIRE gene rs2075876 G>A variant and BC risk in a sample of the Middle East population.
Method In this case-control study, we genotyped AIRE rs2075876 G>A variant in 200 unrelated patients with BC and 340 cancer-free controls using a real-time allelic discrimination polymerase chain reaction. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to estimate the strength of association under several genetic models. In silico analysis of AIRE was also executed.
Results The minor allele (A) frequency of the specified variant accounted for 0.28 in the controls. G/G homozygote was significantly more frequent among patients (94%) compared to controls (66%) (P < .001). After adjusting confounding variables, individuals with A allele conferred protection against developing BC under allelic model (OR = 0.33, 95% CI = 0.20-0.55), recessive model (OR = 0.25, 95% CI = 0.10-0.60), dominant model (OR = 0.12, 95% CI = 0.05-0.29), and homozygote comparison (OR = 0.20, 95% CI = 0.08-0.50). In silico analysis revealed AIRE enrichment in several cancer-related pathways. Kaplan-Meier plotter for the cancer databases showed association of AIRE expression with prognosis in triple-negative BC (HR = 2.44, 95% CI = 1.44-4.15, log-rank P-value < .001).
Conclusion The AIRE rs2075876 G>A variant showed association with BC risk in the study population. Further large-scale replication studies in different ethnicity are warranted to confirm the findings.