title: MicroRNA polymorphisms and environmental smoke exposure as risk factors for oesophageal squamous cell carcinoma.
abstract: 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.
authors.affiliation: 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.
authors.forename: Yabing
authors.initials: Y
authors.lastname: Wang
authors.forename: Matjaz
authors.initials: M
authors.lastname: Vogelsang
authors.forename: Georgia
authors.initials: G
authors.lastname: Schäfer
authors.forename: Marco
authors.initials: M
authors.lastname: Matejcic
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Parker
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D013019:South Africa; D014028:Tobacco Smoke Pollution / Q000009:adverse effects
chemical_list: D035683:MicroRNAs; D014028:Tobacco Smoke Pollution