Arreola Cruz Alejandro, Navarro Hernández Juan Carlos, Cisneros Garza Laura Estela, Miranda Duarte Antonio, Mata Tijerina Viviana Leticia, Hernández Garcia Magda Elizabeth, Peñuelas-Urquides Katia, González-Escalante Laura Adiene, Bermúdez de León Mario, Silva Ramirez Beatriz
Department of Gastroenterology and Hepatology, High Specialty Medical Unit 25, Mexican Social Security Institute, Monterrey 64320, NL, Mexico.
Department of Genomic Medicine, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City 14389, Mexico.
Int J Mol Sci. 2025 Aug 1;26(15):7409. doi: 10.3390/ijms26157409.
Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer with an increasing incidence worldwide. Single nucleotide polymorphisms (SNPs) may influence disease risk and serve as predictive markers. This study aimed to evaluate the association of (rs738409 and rs2294918), (rs780094), (rs641738), (rs2228603), and (rs58542926) SNPs with the risk of developing HCC in a Mexican population. A case-control study was conducted in unrelated Mexican individuals. Cases were 173 adults with biopsy-confirmed HCC and 346 were healthy controls. Genotyping was performed using TaqMan allelic discrimination assay. Logistic regression was applied to evaluate associations under codominant, dominant, and recessive inheritance models. -values were corrected using the Bonferroni test (pC). Haplotype and gene-gene interaction were also analyzed. The GG homozygous of rs738409 and rs2294918 of , TT, and TC genotypes of , as well as the TT genotype of , were associated with a significant increased risk to HCC under different inheritance models (~Two folds in all cases). The genotypes of and did not show differences. The haplotype G-G of rs738409 and rs2294918 of was associated with an increased risk of HCC [OR (95% CI) = 2.2 (1.7-2.9)]. There was a significant gene-gene interaction between (rs738409), (rs780094), and (rs641738) (Cross-validation consistency (CVC): 10/10; Testing accuracy = 0.6084). This study demonstrates for the first time that (rs738409 and rs2294918), (rs780094), and (rs641738) are associated with an increased risk of developing HCC from multiple etiologies in Mexican patients.
肝细胞癌（HCC）是肝癌最常见的亚型，在全球范围内发病率呈上升趋势。单核苷酸多态性（SNP）可能影响疾病风险并可作为预测标志物。本研究旨在评估[具体基因1]（rs738409和rs2294918）、[具体基因2]（rs780094）、[具体基因3]（rs641738）、[具体基因4]（rs2228603）以及[具体基因5]（rs58542926）的SNP与墨西哥人群发生HCC风险的相关性。在无亲缘关系的墨西哥个体中进行了一项病例对照研究。病例为173例经活检确诊的成年HCC患者，346例为健康对照。采用TaqMan等位基因鉴别分析进行基因分型。应用逻辑回归在共显性、显性和隐性遗传模型下评估相关性。P值采用Bonferroni检验（pC）进行校正。还分析了单倍型和基因-基因相互作用。[具体基因1]的rs738409和rs2294918的GG纯合子、[具体基因2]的TT、TC基因型以及[具体基因3]的TT基因型在不同遗传模型下均与HCC风险显著增加相关（所有情况均约为两倍）。[具体基因4]和[具体基因5]的基因型未显示出差异。[具体基因1]的rs738409和rs2294918的单倍型G-G与HCC风险增加相关[比值比（95%可信区间）=2.2（1.7 - 2.9）]。[具体基因1]（rs738409）、[具体基因2]（rs780094）和[具体基因3]（rs641738）之间存在显著的基因-基因相互作用（交叉验证一致性（CVC）：10/10；检验准确性 = 0.6084）。本研究首次证明，[具体基因1]（rs738409和rs2294918）、[具体基因2]（rs780094）和[具体基因3]（rs641738）与墨西哥患者多种病因导致的HCC发生风险增加相关。
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