ArticleGenes & genomics2025
Association of MSH2, MSH6, and MLH1 polymorphisms with susceptibility and survival in lung cancer patients.
Article in Genes & genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundLung 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.
objectiveThis 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.
methodsThis 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.
resultsMultivariate 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.
conclusionrs2303428 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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