Joint association of cytokine gene variants and circulating inflammatory markers with increased breast cancer risk

Abstract The systemic inflammatory milieu, shaped by host genetics, is a key component of the tumor immune microenvironment. This paper anticipated to decode the crosstalk between germline variations in key cytokine genes and their corresponding circulating serum levels in relation to breast cancer risk. The present investigation was conducted involving 160 patients with newly diagnosed breast cancer and 280 matched healthy controls. Serum levels of important cytokines were quantified. Functional polymorphisms in their respective genes (e.g., IL1B -511 C/T, IL6 -1363G/T, IL10 -592 C/A, TNF − 308G/A) were genotyped using PCR-RFLP. Breast cancer patients exhibited significantly elevated levels in IL-1β, IL-6 and TNF-α (all p < 0.001). Multiple polymorphisms were associated with altered disease risk (e.g., IL1B -511TT: OR = 6.39, 95% CI: 2.94–13.87; TNF − 308AA: OR = 2.56, 95% CI: 1.50–4.37). Critically, risk genotypes correlated with higher corresponding serum cytokine concentrations. A significant synergistic interaction was observed between the IL6 genotype and circulating IL-6 level in modulating cancer risk. Our findings suggest a correlation between the germline mutational landscape of immune genes and a pro-tumor systemic immune microenvironment in breast cancer. A synergistic effect between genetic predisposition and inflammatory phenotype was observed. These results indicate that integrated genetic and inflammatory biomarkers may enhance risk assessment and stratification, although prospective validation is needed.