Unveiling the association of sirtuin1 (SIRT1) gene polymorphisms rs3758391 and rs12778366 with the risk, clinicopathological characteristics and susceptibility of breast cancer in Bangladeshi population

Abstract

Breast cancer (BC) is one of the most prevalent malignancies and a leading cause of cancer-related mortality among women worldwide. Genetic variation in the SIRT1 (Sirtuin-1) gene has been implicated in cancer susceptibility; however, evidence regarding its association with breast cancer in the Bangladeshi population remains limited. This study aimed to investigate the association of SIRT1 polymorphisms (rs3758391 and rs12778366) with breast cancer susceptibility and clinicopathological characteristics, while also evaluating demographic and hematological parameters among Bangladeshi women. A hospital-based case-control study was conducted involving 199 histopathologically confirmed breast cancer patients and 100 healthy controls. Genotyping of rs3758391 and rs12778366 was performed using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) technique. Logistic regression analysis was employed to estimate crude and age-adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Herein, significant differences in genotype distributions were observed between cases and controls for both polymorphisms. For rs3758391, individuals carrying the TT genotype showed significantly higher odds of breast cancer under the codominant model (adjusted OR = 4.30, 95% CI: 1.60–11.55, p = 0.004) and recessive model (adjusted OR = 4.76, 95% CI: 1.80–12.59, p = 0.0003) after adjustment for age. In contrast, although the TC + CC genotype of rs12778366 demonstrated increased odds in the dominant model before adjustment (OR = 1.76, p = 0.038), the association lost statistical significance after age adjustment (p = 0.06). Haplotype analysis revealed a significant global association before age adjustment, which became non-significant after adjustment. Among clinicopathological characteristics, rs12778366 TC genotype was significantly associated with progesterone receptor positivity (OR = 3.20, 95% CI: 1.3–8.12, p = 0.012), while no associations were observed with tumor stage. Hematological analysis demonstrated significantly lower hemoglobin levels and elevated erythrocyte sedimentation rate (ESR), neutrophil percentage, plateletcrit (PCT), and mean platelet volume (MPV) in breast cancer patients compared with controls. In conclusion, SIRT1 rs3758391 may serve as a potential genetic susceptibility marker for breast cancer in Bangladeshi women, whereas the association of rs12778366 appears less robust after age adjustment. Larger studies and functional investigations are warranted to validate these findings.