Wang Yabing, Vogelsang Matjaz, Schäfer Georgia, Matejcic Marco, Parker M Iqbal
International Centre for Genetic Engineering and Biotechnology, Cape Town, South Africa Component, UCT Campus, Observatory, Cape Town, South Africa ; IIDMM and Division of Medical Biochemistry, UCT Faculty of Health Sciences, Cape Town, South Africa.
PLoS One. 2013 Oct 21;8(10):e78520. doi: 10.1371/journal.pone.0078520. eCollection 2013.
MicroRNAs (miRNAs) and related polymorphisms have been implicated in the susceptibility to oesophageal squamous cell carcinoma (OSCC). In our study, three miRNA-related SNPs: rs6505162 A>C (pre-miRNA of miR-423), rs213210 A>G (3'UTR of miR-219-1) and rs7372209 C>T (5'UTR of miR-26a-1) were investigated in the Black and Mixed Ancestry population groups in South Africa. The potential cumulative effects of these SNPs, as well as gene-environment interactions were also analysed. In Blacks, rs6505162 A>C was associated with OSCC under dominant, additive and recessive models with odds ratios (ORs) 1.353, 1.404, and 2.858, respectively. This locus showed very strong interactions with smoke inhalation from burning wood or charcoal used for heating and cooking in very poorly ventilated areas (OR(GE)=7.855, P(GE)=9.17*10(-10) in the Black group). Furthermore, the miR-423-3p level was 1.39 fold up-regulated in tumour tissues compared to the adjacent normal tissue (paired t-test P value 0.0087). SNP-SNP interaction between rs2132210 and rs7372209 was found in both Black and Mixed Ancestry subjects. The AArs213210-CTrs7372209 genotype had a protective effect on OSCC risk (in the Black, OR=0.229, P=0.012; and the Mixed Ancestry groups, OR=0.230, P=0.00014). This study is the first to link SNPs in miR-423 together with environmental smoke exposure to risk for developing OSCC.
微小RNA（miRNA）及其相关多态性与食管鳞状细胞癌（OSCC）的易感性有关。在我们的研究中，对南非黑人及混合血统人群组中的三个与miRNA相关的单核苷酸多态性（SNP）进行了研究：rs6505162 A>C（miR-423的前体miRNA）、rs213210 A>G（miR-219-1的3'非翻译区）和rs7372209 C>T（miR-26a-1的5'非翻译区）。还分析了这些SNP的潜在累积效应以及基因-环境相互作用。在黑人中，rs6505162 A>C在显性、加性和隐性模型下与OSCC相关，比值比（OR）分别为1.353、1.404和2.858。该位点与在通风极差的区域使用木材或木炭燃烧取暖和烹饪时吸入烟雾表现出非常强的相互作用（黑人组中OR(GE)=7.855，P(GE)=9.17×10(-10)）。此外，与相邻正常组织相比，肿瘤组织中的miR-423-3p水平上调了1.39倍（配对t检验P值为0.0087）。在黑人和混合血统受试者中均发现了rs2132210和rs7372209之间的SNP-SNP相互作用。AArs213210-CTrs7372209基因型对OSCC风险具有保护作用（在黑人中，OR=0.229，P=0.012；在混合血统组中，OR=0.230，P=0.00014）。本研究首次将miR-423中的SNP与环境烟雾暴露联系起来，表明其与OSCC发生风险相关。
