Sarani Hosna, Taheri Mohsen, Jahantigh Danial, Keramati Mohammad Reza, Hashemi Seyed Mehdi, Bahari Gholamreza, Taheri Saba
Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Iran.
Children and Adolescent Health Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan , Iran.
Asian Pac J Cancer Prev. 2025 Jan 1;26(1):137-145. doi: 10.31557/APJCP.2025.26.1.137.
LIN28, a highly conserved RNA-binding protein, regulate a wide variety of post-transcriptional cellular processes. The current study aimed to identify genetic variants of five single nucleotide polymorphisms (SNPs) in the LIN28B gene (rs221634, rs22163, rs314276, rs9404590, and rs12194974) and their association with Breast cancer.
220 patients and 230 controls were genotyped by the RFLP assay for Lin28B gene variants. Odds ratio analysis was used to determine the association between Lin28B variants and breast cancer. Haplotype analysis was performed to determine the combined impact of the investigated variants on BC. Novel in-silico analysis were performed to predict the potential functions of these polymorphisms, as well.
Patients carrying all variant genotypes for lin28B rs221634 (codominant, dominant, recessive, and allelic inheritance models), rs221635 (codominant and dominant genotypes), and rs9404590 (codominant, dominant, and inheritance model). Significant associations between reduced cancer risk and rs12194974 and rs314276 were found in codominant, dominant, recessive, and allele inheritance models. According to haplotype analysis of rs9404590, rs12194974, rs314276, rs221634, and rs221635 SNPs ,the GGCTT, GGCAT, TGCAC, TGCTC, GGCAC, GGCTC, and GGAAC haplotypes are associated with an increased risk of BC, whereas the TACAT and TAAAT haplotypes were associated with a decreased risk of BC. The splicing enhancers (ESE) binding site was found to be altered by the SNPs rs9404590, rs12194974, and rs314276, according to in-silico analysis.
Breast cancer susceptibility appears to be linked to genetic variations in the Lin28B gene, and haplotypes in this region have been linked to increased risk.
LIN28是一种高度保守的RNA结合蛋白，可调节多种转录后细胞过程。本研究旨在鉴定LIN28B基因中五个单核苷酸多态性（SNP）（rs221634、rs22163、rs314276、rs9404590和rs12194974）的基因变异及其与乳腺癌的关联。
采用RFLP分析法对220例患者和230例对照进行Lin28B基因变异的基因分型。采用比值比分析确定Lin28B变异与乳腺癌之间的关联。进行单倍型分析以确定所研究变异对乳腺癌的综合影响。还进行了新的计算机模拟分析以预测这些多态性的潜在功能。
携带lin28B rs221634所有变异基因型的患者（共显性、显性、隐性和等位基因遗传模型）、rs221635（共显性和显性基因型）和rs9404590（共显性、显性和遗传模型）。在共显性、显性、隐性和等位基因遗传模型中发现rs12194974和rs314276与降低癌症风险之间存在显著关联。根据rs9404590、rs12194974、rs314276、rs221634和rs221635 SNPs的单倍型分析，GGCTT、GGCAT、TGCAC、TGCTC、GGCAC、GGCTC和GGAAC单倍型与乳腺癌风险增加相关，而TACAT和TAAAT单倍型与乳腺癌风险降低相关。根据计算机模拟分析，发现rs9404590、rs12194974和rs314276的SNP改变了剪接增强子（ESE）结合位点。
乳腺癌易感性似乎与Lin28B基因的遗传变异有关，该区域的单倍型与风险增加有关。
