Association between SIRT1 rs3758391 genetic variant and susceptibility to pancreatic and gastric cancer

BackgroundThe SIRT1 gene encodes a NAD⁺-dependent deacetylase that regulates apoptosis, metabolism and genomic stability through interaction with p53 and other transcription factors.Functional single nucleotide polymorphisms within SIRT1 may alter gene expression and affect cancer susceptibility.The rs3758391 and rs369274325 polymorphisms have been implicated in various malignancies; however, their role in pancreatic and gastric cancer remains unclear.Methods This case-control study included 94 patients with pancreatic ductal adenocarcinoma (PDAC), 38 patients with gastric cancer (GC), and 74 healthy controls, all of Greek origin.Genomic DNA was extracted from peripheral blood samples.Genotyping was performed by RFLP-PCR for rs3758391 and tetra-primer ARMS-PCR for rs369274325.Genotype and allele frequencies were compared using χ 2 test and odds ratios (ORs) with 95% confidence intervals (CIs).Results A significant association was identified between SIRT1 rs3758391 and PDAC and GC susceptibility.The TT genotype was overrepresented among PDAC patients, while the TC genotype conferred a protective effect against both PDAC (P=0.0039;OR 0.35, 95%CI 0.17-0.62)and GC (P=0.0059;OR 0.26, 95%CI 0.10-0.66).The C allele was more frequent in healthy controls compared to PDAC patients (P