Methylenetetrahydrofolate reductase polymorphic variants C677T and A1298C in rectal cancer in Slavic population: significance for cancer risk and response to chemoradiotherapy

• DOI: 10.3389/fgene.2023.1299599
• Publication Date: 2024-01-15T04:13:16Z
• Authors: Aleksandra Stanoj...; Jelena Spasic; Mladen Marinkovic; Suzana Stojanovic...; Radmila Jankovic; Ana Djuric; Jerome Zoidakis; Remond J. A. Fijn...; Sergi Castellvi-Bel; Milena Cavic
• Keywords: Chemoradiotherapy

Background: Methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms (SNPs) have been suggested as risk, prognostic, and predictive factors for colorectal cancer in various populations, but not validated so far. The aim of this study was to examine the association MTHFR C677T (rs1801133) A1298C (rs1801131) with risk rectal well response neoadjuvant chemoradiotherapy (nCRT) based on 5-Fluorouracil (5-FU)/leucovorin (LV) locally advanced setting. Patients methods: This case-control included 119 healthy controls 97 patients (LARC). For genotyping, restriction fragment length polymorphism analysis (PCR-RFLP) employed. Results: In silico highlighted that SNPs A1298T correlate gene expression, expression profile correlates stage. Using dominant recessive models, it found 677CC vs. 677CT+677TT increased development (odds ratio (OR): 2.27; 95% confidence interval (CI): 1.30-3.95, p = 0.002) 677CC+677CT compared 677TT (OR: 4.18, CI: 1.16-14.99, 0.014). 1298AA also shown 1298AC+1298CC (OR:2.0, 1.20-3.59, 0.035) Statistical combined genotypes protective role CT/AC genotype 3.15 1.576-6.279, while CC/AA showed an 2.499, 1.246-5.081, 0.016) carriers 677C/1298A haplotype had highest developing 1.74; 1.198-2.530, 677T/1298C seems provide a effect. 0.44; 95%CI 0.248-0.795, 0.003). No significant found. Conclusion: Our data point 667C allele 1298A alleles low-penetrance our population. To best knowledge, is first type performed Slavic population Western Balkan, population-based might be findings can used future meta-analyses construction genetic prediction panels.