Department of Respiratory Medicine, The First Affiliated Hospital of School of Medicine of Xi'an Jiaotong University, Yanta District, No. 277, Yanta West Road, Xi'an, 710061, Shaanxi, China.
Department of Blood Transfusion, The First People's Hospital of Yunnan Province, The Afiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, Yunnan, China.
BMC Cancer. 2024 Jun 28;24(1):778. doi: 10.1186/s12885-024-12516-y.
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.
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.
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/m, 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.
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.
金属调节转录因子 1(MTF1)是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来调节癌细胞的增殖,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,而 MTF1 高表达与 LC 的良好预后相关。然而,MTF1 多态性与 LC 风险之间的关联尚未得到探索。
采用 Agena MassARRAY 系统对 670 例健康对照和 670 例 LC 患者的 MTF1 单核苷酸多态性(SNP)包括 rs473279、rs28411034、rs28411352 和 rs3748682 进行基因分型。采用 logistic 回归计算比值比(OR)和 95%置信区间(CI),以评估这些 SNP 与 LC 风险的关系。
MTF1 rs28411034(OR 1.22,95%CI 1.03-1.45,p=0.024)和 rs3748682(OR 1.24,95%CI 1.04-1.47,p=0.014)与整体较高的 LC 易感性相关。此外,rs28411034 和 rs3748682 对 LC 易感性的影响仅见于男性、BMI≥24kg/m2、吸烟者、饮酒者和肺鳞癌患者(OR 和 95%CI>1,p<0.05)。此外,rs28411352(OR 0.73,95%CI 0.55-0.97,p=0.028)对饮酒者 LC 风险降低有保护作用。
我们首次报道 rs28411034 和 rs3748682 在中国汉族人群中与 LC 易感性增加相关。本研究结果有助于认识 MTF1 基因在 LC 进展中的致病机制。