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.

The association between miR-423 rs6505162 polymorphism and cancer susceptibility: a systematic review and meta-analysis

“…Two studies concluded that the A allele of the rs6505162 increased the risk of breast cancer, [22, 24] whereas the same allele presented a decreased risk of developing lung cancer and bladder cancer in two other studies [30, 32]. The inconsistent effect for the A allele was also observed among three esophageal cancer studies [26–28]. Meta-analysis, as a powerful statistical method, could provide a quantitative approach for pooling the results of different studies on the same topic and estimating the diversity.…”

HIV infection and domestic smoke exposure, but not human papillomavirus, are risk factors for esophageal squamous cell carcinoma in Zambia: a case–control study

“…There are no published data on the genetics and risk factors for OSCC in Zambia, although in studies within the region (South Africa and Uganda), smoking has been reported to play a major role in esophageal cancer 3 , 31 , 33 . However, there is a need to further evaluate the relationship between gene susceptibility and lifestyle risk factors such as smoking 34 . We found a highly significant association between cigarette smoking and OSCC.…”

A Genetic Variant in miRNA-219-1 Is Associated with Risk of Esophageal Squamous Cell Carcinoma in Chinese Kazakhs

“…Carcinogenesis and development of ESCC are complex biological processes involving multiple factors, including environmental risk factors. ESCC is a polygenic hereditary disease that can also be influenced by genetic factors [ 5 , 14 , 30 , 31 ]. Along with other researchers, we have long carried on the etiological and epidemiological investigation of numerous aspects of the high Kazakh ESCC incidence rate, which may include traditional habits and customs, such as eating hot meals, hard foods, yogurt knots, and tea; smoking; lack of folic acid; natural geographical environment [ 31 ]; genetic factors, such as PLCE1, hRFT1, and ECRG2 [ 14 , 32 , 33 ]; and microbial factors, such as HPV [ 34 ].…”

“…SNP in miRNA genes, a common type of genetic variation in the human genome, was associated with different types of cancer susceptibility [ 5 , 15 , 26 , 35 ], as SNP can play a predictive role in the risk of cancer development and clarify the pathophysiological mechanism of carcinogenesis. Several studies have linked the miR-219-1 SNP to cancer susceptibility [ 24 , 27 – 29 ].…”

“…Esophageal cancer (EC), an aggressive digestive tract malignancy, is one of the leading causes of cancer-related deaths worldwide [ 1 – 5 ]. The two major histologic types of EC are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) [ 1 , 3 , 6 – 8 ].…”