Interleukin-1β rs16944 Polymorphism and Human Cytomegalovirus Seropositivity as Genetic and Viral Risk Determinants of Female Breast Cancer

Document Type : Research Articles

Authors

1 Microbiology Department, Academic Center for Epidemiological Diseases, Kufa, Iraq.

2 Jabir ibn Hayyan University for Medical and Pharmaceutical Sciences, Iraq.

Abstract

Background: Breast cancer is the most frequently diagnosed malignancy in women worldwide. Human cytomegalovirus (HCMV) has been implicated as an oncomodulatory agent in mammary carcinogenesis, and the Interleukin1β −511C>T polymorphism (rs16944) is associated with altered inflammatory signaling and cancer susceptibility. Objective: To investigate the association between IL1β rs16944 polymorphism and HCMV and breast cancer risk in patients with fibroadenoma compared to healthy controls. Materials and Methods: We conducted a hospital-based case-control study that enrolled 120 Iraqi women: 60 with breast cancer, 30 with fibroadenoma, and 30 healthy controls. HCMV IgG levels were quantified using the VIDAS® immunoassay. Serum IL-1β and IL-6 levels were measured using sandwich ELISA. The rs16944 polymorphism was genotyped using Tetra-ARMS PCR, and HCMV DNA was confirmed using UL55 conventional PCR. Haematological parameters were assessed using automated analysis. Results: HCMV IgG seropositivity was significantly higher in breast cancer patients (81.7%) than in those with fibroadenoma (63.3%) and controls (60.0%) (p = 0.04), with HCMV DNA confirmed by UL55 PCR. Serum IL-6 levels were elevated in breast cancer (486.6 ± 228 pg/mL) and those with fibroadenoma (467 ± 225 pg/mL) compared to controls (184.5 ± 58.3 pg/mL; p < 0.0001). IL-1β levels were paradoxically lower in breast cancer patients (891 ± 178.4 pg/mL; p < 0.0001). The rs16944 TT genotype was more common in breast cancer (35.0%) than in controls (20.0%) (χ² = 10.20, p = 0.0377). Conclusion: HCMV seropositivity and the IL1β rs16944 TT genotype are independently associated with breast cancer in an Iraqi female cohort, indicating that the convergence of viral infection and pro-inflammatory genetic predisposition may potentiate carcinogenic risk. The paradoxical suppression of systemic IL-1β reflects cytokine compartmentalization in malignancy.

Keywords

Main Subjects