Impact of Interleukin-12B Genotypes on Breast Cancer Risk

Breast cancer (BC) remains the leading cause of cancer-related mortality among women worldwide. Interleukin-12 (IL-12), a cytokine pivotal in immune regulation, has shown antitumor properties and may contribute to BC pathogenesis.

This study investigated the association between IL-12B rs3212227 polymorphism and BC risk in a Taiwanese population comprising 1,232 BC patients and 1,232 age-matched cancer-free controls.

Genotype frequencies among controls conformed to Hardy-Weinberg equilibrium (p=0.0581). Compared to the AA genotype, carriers of the AC (OR=0.88, 95%CI=0.73-1.06, p=0.2105) and CC (OR=0.84, 95%CI=0.68-1.04, p=0.1307) genotypes exhibited a non-significant reduction in BC susceptibility. Similarly, neither dominant (AC+CC versus AA: OR=0.87, 95%CI=0.73-1.03, p=0.1225) nor recessive (CC versus AA+AC: OR=0.90, 95%CI=0.75-1.09, p=0.3198) models reached statistical significance. Allelic analysis showed a marginally reduced risk associated with the C allele (OR=0.91, 95%CI=0.81-1.02, p=0.1038). Notably, age-stratified analysis revealed significant protective effects of the AC (OR=0.79, 95%CI=0.64-0.98, p=0.0331) and CC (OR=0.68, 95%CI=0.52-0.87, p=0.0034) genotypes in individuals aged ≤55 years, but not in older subjects. No significant associations were found between IL-12B rs3212227 and risk of triple-negative BC (TNBC) or non-TNBC subtypes (p for trend=0.2072 and 0.8291, respectively).

IL-12B rs3212227 is not a major genetic determinant of overall BC susceptibility in this population but may exert age-dependent protective effects. Further studies integrating IL-12 expression profiling and additional IL-12 pathway variants are warranted to clarify the immunogenetic basis of BC.