Introduction: Breast cancer, a prevalent global health concern, involves complex molecular mechanisms. SIRT1, a key protein involved in cellular regulation, exhibits altered expression in breast cancer. Its intricate mechanism includes influencing DNA repair, apoptosis, and cell survival pathways, contributing to breast cancer development and progression.

Objectives: We aimed to compare SIRT1 expression, assess variant patterns, and explore the association of SIRT1 polymorphisms with their expression and clinical staging of breast cancer.

Methodology: This cross-sectional study enrolled 172 breast cancer patients and 78 age-matched healthy females. Breast cancer patients were further divided into three groups based on their hormone receptor status: 76 hormone-positive patients (ER+ve, PR+ve), 20 triple-negative breast cancer (TNBC), and 76 HER+ve cases. Blood samples were collected for DNA isolation and serum analysis. RFLP/Sequencing determined mutations, and ELISA quantified serum Sirtuin 1 levels. Ethical approval was obtained before conducting the study.

Results: Significantly elevated serum Sirtuin 1 levels were found in breast cancer patients compared to healthy females (p = 0.0027). Subgroup analyses revealed notable increases in HER-positive (p = 0.0001), hormone-positive (p = 0.0001), and TNBC groups (p = 0.0094) compared to the control group. However, no significant variations were noted across different breast cancer stages. The SIRT1 variant rs141528984 exhibited a significant association with breast cancer (p = <0.0001). The association of SIRT1 variants with clinical staging and breast cancer types did not show significant differences. Also, SIRT1 levels did not significantly vary with tumor grade, lymph node involvement, or metastasis. The proliferation marker Ki67 demonstrated a significant association (p = 0.0428) with the specific SIRT1 variants rs777323664, rs757804740, and rs1842828683. The association between SIRT1 gene polymorphisms and Sirtuin 1 levels did not show any significant difference either.

Conclusion: This study suggests that elevated Sirtuin-1 levels may serve as potential markers for breast carcinoma. The intricate relationships between SIRT1 expression, polymorphisms, and clinical staging warrant further investigation for comprehensive insights into breast cancer.