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.
Related
- Targeting the IL-23 pathway in inflammatory bowel disease: from cytokine inhibition to oral IL-23 receptor blockade.
- LL-37 and Citrullinated-LL-37 elicited Transcriptome and Cytokine Profiles in Human Bronchial Epithelial Cells: Citrullination dampens the inflammatory biosignature
- Cytokine profiles of aqueous humor from sequential bilateral cataract surgery: Impact of diabetes on inflammatory responses
- A transcriptomic atlas of macrophage polarization induced by inflammatory and reparative cytokines reveals cytokine-specific and synergistic polarization programs
- Unmet social needs in pediatric patients with inflammatory bowel disease linked to increased risk of missed appointments
BibTeX
@article{zheng2026joint,
title = {{Joint association of cytokine gene variants and circulating inflammatory markers with increased breast cancer risk}},
author = {Shuya Zheng and Fuqiang Cui and Jun Qin and Zhiqiang Liu},
journal = {Scientific Reports},
year = {2026},
month = sep,
doi = {10.1038/s41598-026-72258-8},
url = {https://www.nature.com/articles/s41598-026-72258-8},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Joint association of cytokine gene variants and circulating inflammatory markers with increased breast cancer risk
AU - Shuya Zheng
AU - Fuqiang Cui
AU - Jun Qin
AU - Zhiqiang Liu
PY - 2026
DA - 2026/09/30
JO - Scientific Reports
DO - 10.1038/s41598-026-72258-8
UR - https://www.nature.com/articles/s41598-026-72258-8
AB - 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.
SN - 2045-2322
ER -