Association of MSH2, MSH6, and MLH1 polymorphisms with susceptibility and survival in lung cancer patients.

IF 1.7 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & genomics Pub Date : 2025-09-10 DOI:10.1007/s13258-025-01681-4

Jing Cheng, Chao Zuo, Dongli Yang, Yi Liu, Yu Wang, Yongchao Qiao

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引用次数: 0

Abstract

Background: Lung cancer (LC) is the leading cause of cancer-related deaths globally. Genetic variants in mismatch repair (MMR) genes, such as MutS homolog 2 (MSH2), MutS homolog 6 (MSH6) and MutL homolog 1 (MLH1), may influence individual susceptibility and clinical outcomes in LC.

Objective: This study investigated the associations of genetic polymorphisms in MSH2, MSH6, and MLH1 with susceptibility and survival outcomes in lung cancer patients in the Guangxi Zhuang population.

Methods: This study included a cohort of 192 LC patients and 262 healthy controls. The association of MSH2, MSH6, and MLH1 polymorphisms with susceptibility to small cell lung cancer (SCLC), lung adenocarcinoma (LUAD), and lung squamous carcinoma (LUSC) was evaluated using case-control methods, and protein expression differences were analysed by immunohistochemistry. The genotypes of genetic variations were detected using high-throughput SNP-scan technology. The Kaplan-Meier survival curve and log-rank test were used to assess the influence of individual genetic variants on prognostic outcomes in lung cancer patients.

Results: Multivariate logistic regression identified significant associations of rs2303428 and rs1042821 with increased lung cancer risk, especially in SCLC and LUSC. The GA and GG genotypes of rs1042821 were linked to higher SCLC risk (OR = 4.415 and 2.685; P = 0.019), the TC genotype of rs2303428 was associated with elevated LUSC risk (OR = 3.993; P = 0.034). No associations were found for rs1800734 or in LUAD. Immunohistochemistry showed increased MSH2 and MSH6 expression in risk genotypes, with no genotype-related changes in MLH1. In LUAD, the CC genotype of rs2300789 was associated with poorer overall survival compared to TC (P = 0.047), with no significant differences in other comparisons.

Conclusion: rs2303428 and rs1042821 polymorphisms were associated with increased lung cancer susceptibility and altered protein expression. Additionally, the CC genotype of rs2300789 was linked to poorer overall survival in LUAD.

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MSH2、MSH6和MLH1基因多态性与肺癌患者易感性和生存率的关系

背景：肺癌（LC）是全球癌症相关死亡的主要原因。错配修复（MMR）基因的遗传变异，如MutS同源物2 （MSH2）、MutS同源物6 （MSH6）和MutL同源物1 (MLH1)，可能影响LC的个体易感性和临床结果。目的：探讨广西壮族肺癌患者MSH2、MSH6和MLH1基因多态性与易感性和生存结局的关系。方法：本研究纳入了192例LC患者和262例健康对照。采用病例对照法评估MSH2、MSH6和MLH1多态性与小细胞肺癌（SCLC）、肺腺癌（LUAD）和肺鳞癌（LUSC）易感性的关系，并通过免疫组织化学分析蛋白表达差异。采用高通量snp扫描技术检测遗传变异的基因型。Kaplan-Meier生存曲线和log-rank检验用于评估个体遗传变异对肺癌患者预后的影响。结果：多因素logistic回归发现rs2303428和rs1042821与肺癌风险增加显著相关，尤其是在SCLC和LUSC中。rs1042821的GA和GG基因型与SCLC风险升高相关（OR = 4.415和2.685,P = 0.019）， rs2303428的TC基因型与LUSC风险升高相关（OR = 3.993, P = 0.034）。rs1800734或LUAD未发现关联。免疫组化显示MSH2和MSH6在危险基因型中表达升高，而MLH1基因型无相关变化。在LUAD中，与TC相比，rs2300789的CC基因型与较差的总生存率相关（P = 0.047），其他比较无显著差异。结论：rs2303428和rs1042821多态性与肺癌易感性增加和蛋白表达改变相关。此外，rs2300789的CC基因型与LUAD患者较差的总生存率有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genes & genomics 生物-生化与分子生物学

CiteScore

3.70

自引率

4.80%

发文量

131

审稿时长

6-12 weeks

期刊介绍： Genes & Genomics is an official journal of the Korean Genetics Society (http://kgenetics.or.kr/). Although it is an official publication of the Genetics Society of Korea, membership of the Society is not required for contributors. It is a peer-reviewed international journal publishing print (ISSN 1976-9571) and online version (E-ISSN 2092-9293). It covers all disciplines of genetics and genomics from prokaryotes to eukaryotes from fundamental heredity to molecular aspects. The articles can be reviews, research articles, and short communications.