Qu Yan, Shao Na, Yang Wenjing, Wang Jianbo, Cheng Yufeng
Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, People's Republic of China,
Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, People's Republic of China.
Onco Targets Ther. 2019 Apr 3;12:2495-2503. doi: 10.2147/OTT.S191155. eCollection 2019.
The main aim of this study was to investigate the association of polymorphisms in long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) with the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese population.
A total of 245 ESCC patients and 490 gender- and age-matched cancer-free controls were genotyped for four tag single nucleotide polymorphisms (SNPs) of MALAT1 (rs3200401 C > T, rs1122709 C > G, rs664589 C > G, and rs619586 A > G). Statistical analyses including chi-squared test and logistic regression were performed to identify the association between the tag SNPs and risk of ESCC, and false discovery rate (FDR) <25% was applied to adjust for multiple comparisons.
We found that rs3200401 C > T polymorphism of MALAT1 was significantly associated with increased risk of ESCC (CT vs CC: adjusted OR =1.59, 95% CI =1.07-2.35, =0.021; TT vs CC: adjusted OR =2.27, 95% CI =1.04-4.96, =0.039; dominant model [CT+TT vs CC]: adjusted OR =1.68, 95% CI =1.16-2.43, =0.006). In the stratified analysis, rs3200401 TT and CT/TT genotypes were associated with increased risk of ESCC compared with CC genotype in subgroup of never drinking (TT vs CC: adjusted OR =2.34, 95% CI =1.02-5.34, =0.044; CT/TT vs CC: adjusted OR =1.52, 95% CI =1.02-2.26, =0.041). However, compared with AA genotype, MALAT1 rs619586 GG was associated with decreased risk of ESCC in ever drinking subgroup (GG vs AA: adjusted OR =0.38, 95% CI =0.15-0.99, =0.049). The results remained significant after FDR adjustment (FDR value <0.25) except for the comparison between rs619586 GG and AA genotype in ever drinking subgroup.
Taken together, our findings proposed that polymorphism rs3200401 C > T in MALAT1 gene is associated with increased risk of ESCC. Since the association between rs619586 A > G polymorphism and ESCC risk was not significant after FDR adjustment, there was a minor possibility that rs619586 A > G might be a protective factor for ESCC.
本研究的主要目的是在中国人群中调查长链非编码RNA转移相关肺腺癌转录本1（MALAT1）的多态性与食管鳞状细胞癌（ESCC）风险之间的关联。
对245例ESCC患者和490例年龄及性别匹配的无癌对照进行MALAT1的4个标签单核苷酸多态性（SNP）（rs3200401 C>T、rs1122709 C>G、rs664589 C>G和rs619586 A>G）基因分型。进行包括卡方检验和逻辑回归在内的统计分析，以确定标签SNP与ESCC风险之间的关联，并应用错误发现率（FDR）<25%来调整多重比较。
我们发现MALAT1的rs3200401 C>T多态性与ESCC风险增加显著相关（CT与CC：调整后的OR=1.59，95%CI=1.07-2.35，P=0.021；TT与CC：调整后的OR=2.27，95%CI=1.04-4.96，P=0.039；显性模型[CT+TT与CC]：调整后的OR=1.68，95%CI=1.16-2.43，P=0.006）。在分层分析中，与CC基因型相比，rs3200401 TT和CT/TT基因型在从不饮酒亚组中与ESCC风险增加相关（TT与CC：调整后的OR=2.34，95%CI=1.02-5.34，P=0.044；CT/TT与CC：调整后的OR=1.52，95%CI=1.02-2.26，P=0.041）。然而，与AA基因型相比，MALAT1 rs619586 GG在曾经饮酒亚组中与ESCC风险降低相关（GG与AA：调整后的OR=0.38，95%CI=0.15-0.99，P=0.049）。除了曾经饮酒亚组中rs619586 GG与AA基因型的比较外，FDR调整后结果仍然显著（FDR值<0.25）。
综上所述，我们的研究结果表明MALAT1基因中的多态性rs3200401 C>T与ESCC风险增加相关。由于FDR调整后rs619586 A>G多态性与ESCC风险之间的关联不显著，rs619586 A>G有可能是ESCC的一个保护因素。
