Klusek Justyna, Lewitowicz Piotr, Nowak-Starz Grażyna, Witczak Bartosz, Oblap Ruslan, Kozieł Dorota, Nasierowska-Guttmejer Anna, Klusek Jolanta, Jóźwik Artur, Rogula Tomasz, Kocańda Kamila, Głuszek Stanisław
Collegium Medicum, Jan Kochanowski University, 25-369 Kielce, Poland.
Faculty of Medicine, Lazarski University, 02-662 Warszawa, Poland.
J Clin Med. 2025 Jun 2;14(11):3912. doi: 10.3390/jcm14113912.
Colorectal cancer (CRC), the most common malignancy of the gastrointestinal tract, is the second leading cause of cancer-related deaths worldwide. In this context, investigating low-penetrance gene variants associated with the increased risk of CRC represents a novel and crucial approach to enhancing prevention strategies and clinical surveillance. By focusing on these genetic variants, there is potential for more accurate prediction of individual CRC risk, which could contribute to the refinement of current screening and prophylactic programs. The aim of this case-control study was to explore the association between SIRT1 polymorphisms and CRC risk. We analyzed three SNPs-rs12778366 (T/C), rs3758391 (C/T), and rs7895833 (A/G)-in the promoter region of the SIRT1 gene, which may influence SIRT1 expression and thus play a role in cancer development. Our study included 200 patients with colorectal adenocarcinoma and 115 controls. Genomic DNA was extracted from blood samples, and SIRT1 SNP analysis was performed using the qPCR method and endpoint genotyping. Univariate regression analysis revealed a slightly increased risk of developing CRC in individuals with minor alleles of the analyzed polymorphisms; however, the observed differences were not statistically significant. Although our findings did not reveal statistically significant differences in SIRT1 gene polymorphism frequencies between the CRC group and the control group, we observed a tendency that suggests further investigation in larger cohorts is warranted. This research underscores the importance of understanding low-penetrance genetic factors in CRC, highlighting their potential to inform more personalized and effective prevention strategies.
结直肠癌（CRC）是胃肠道最常见的恶性肿瘤，是全球癌症相关死亡的第二大主要原因。在此背景下，研究与CRC风险增加相关的低 penetrance 基因变异代表了一种新颖且关键的方法，可用于加强预防策略和临床监测。通过关注这些基因变异，有可能更准确地预测个体的CRC风险，这有助于完善当前的筛查和预防计划。本病例对照研究的目的是探讨SIRT1基因多态性与CRC风险之间的关联。我们分析了SIRT1基因启动子区域的三个单核苷酸多态性（SNPs）——rs12778366（T/C）、rs3758391（C/T）和rs7895833（A/G），这些可能会影响SIRT1的表达，从而在癌症发展中发挥作用。我们的研究包括200例结直肠腺癌患者和115名对照。从血样中提取基因组DNA，并使用qPCR方法和终点基因分型进行SIRT1 SNP分析。单变量回归分析显示，具有所分析多态性次要等位基因的个体患CRC的风险略有增加；然而，观察到的差异无统计学意义。虽然我们的研究结果未显示CRC组和对照组之间SIRT1基因多态性频率存在统计学上的显著差异，但我们观察到一种趋势，表明有必要在更大的队列中进一步研究。这项研究强调了了解CRC中低 penetrance 遗传因素的重要性，突出了它们为更个性化和有效的预防策略提供信息的潜力。
