关键词: MTF1 variants Clinical features Demographic characteristics Lung cancer Stratification analysis Susceptibility

Mesh : Humans Lung Neoplasms / genetics Male Polymorphism, Single Nucleotide Female Genetic Predisposition to Disease Middle Aged Transcription Factors / genetics Asian People / genetics DNA-Binding Proteins / genetics Transcription Factor MTF-1 Case-Control Studies China / epidemiology Aged Genotype Risk Factors East Asian People

来  源:   DOI:10.1186/s12885-024-12516-y   PDF(Pubmed)

Abstract:
BACKGROUND: Metal-regulatory transcription factor 1 (MTF1), a conserved metal-binding transcription factor in eukaryotes, regulates the proliferation of cancer cells by activating downstream target genes and then participates in the formation and progression of tumors, including lung cancer (LC). The expression level of MTF1 is down-regulated in LC, and high expression of MTF1 is associated with a good prognosis of LC. However, the association between MTF1 polymorphism and LC risk has not been explored.
METHODS: The genotyping of MTF1 Single nucleotide polymorphisms (SNPs) including rs473279, rs28411034, rs28411352, and rs3748682 was identified by the Agena MassARRAY system among 670 healthy controls and 670 patients with LC. The odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistics regression to assess the association of these SNPs with LC risk.
RESULTS: MTF1 rs28411034 (OR 1.22, 95% CI 1.03-1.45, p = 0.024) and rs3748682 (OR 1.24, 95% CI 1.04-1.47, p = 0.014) were associated with higher LC susceptibility overall. Moreover, the effect of rs28411034 and rs3748682 on LC susceptibility was observed in males, subjects with body mass index (BMI) ≥ 24 kg/m2, smokers, drinkers, and patients with lung squamous carcinoma (OR and 95% CI > 1, p < 0.05). Besides, rs28411352 (OR 0.73, 95% CI 0.55-0.97, p = 0.028,) showed protective effect for reduced LC risk in drinkers.
CONCLUSIONS: We were first who reported that rs28411034 and rs3748682 tended to be relevant to increased LC susceptibility among the Chinese Han population. These results of this study could help to recognize the pathogenic mechanisms of the MTF1 gene in LC progress.
摘要:
背景:金属调节转录因子1(MTF1),真核生物中保守的金属结合转录因子,通过激活下游靶基因调节癌细胞的增殖,进而参与肿瘤的形成和进展,包括肺癌(LC)。LC中MTF1的表达水平下调,MTF1的高表达与LC的良好预后有关。然而,MTF1多态性与LC风险之间的关联尚未研究.
方法:AgenaMassARRAY系统在670名健康对照和670名LC患者中鉴定了MTF1单核苷酸多态性(SNP)的基因分型,包括rs473279,rs28411034,rs28411352和rs3748682。通过后勤回归计算比值比(OR)和95%置信区间(CI),以评估这些SNP与LC风险的关联。
结果:MTF1rs28411034(OR1.22,95%CI1.03-1.45,p=0.024)和rs3748682(OR1.24,95%CI1.04-1.47,p=0.014)与较高的LC总体易感性相关。此外,rs28411034和rs3748682对LC易感性的影响在男性中观察到,体重指数(BMI)≥24kg/m2的受试者,吸烟者,饮酒者,和肺鳞癌患者(OR和95%CI>1,p<0.05)。此外,rs28411352(OR0.73,95%CI0.55-0.97,p=0.028,)显示出降低饮酒者LC风险的保护作用。
结论:我们首先报道了rs28411034和rs3748682与中国汉族人群中LC易感性增加有关。本研讨的这些成果有助于辨认MTF1基因在LC进程中的致病机制。
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