The Association of MEG3 Gene rs7158663 Polymorphism With Cancer Susceptibility

Abstract

Although the association of MEG3 gene rs7158663 polymorphism with cancer susceptibility has been investigated, the findings are inconsistent. The aim of this study was to analyze the association between the rs7158663 polymorphism and cancer susceptibility through a case-control study and meta-analysis. In a case-control study with 430 colorectal cancer (CRC) cases and 445 healthy controls, the rs7158663 polymorphism was genotyped by direct sequencing. STATA software was used to calculate the pooled odds ratio and 95% confidence interval in a meta-analysis including 4,649 cancer cases and 5,590 controls. Both the case-control study and meta-analysis showed that the rs7158663 polymorphism was associated with increased susceptibility to CRC. Individuals carrying the AA or GA genotype were more likely to develop CRC than those carrying the rs7158663 GG genotype. Interestingly, MEG3 expression was significantly lower in colorectal tissues of the AA or GA genotype compared to those of the rs7158663 GG genotype. In addition, the meta-analysis suggested that the rs7158663 polymorphism was also associated with increased susceptibility to breast cancer and gastric cancer. Bioinformatics analysis showed that the rs7158663 A allele contributed to the binding of hsa-miR-4307 and hsa-miR-1265 to MEG3. In conclusion, the current findings suggest that the MEG3 gene rs7158663 polymorphism may serve as a genetic marker for predicting the risk of cancers, such as breast cancer, gastric cancer and CRC. However, the sample size of the current study is still insufficient, especially in the subgroup analysis. Therefore large and well-designed studies are needed to validate our findings.

Association of lncRNA MEG3 rs941576 polymorphism, expression profile, and its related targets with the risk of obesity-related colorectal cancer: potential clinical insights

“…Evidence of the association of MEG3 genetic variants with CRC risk was unraveled in previous research 17 , 49 , 50 . The MEG3 rs7158663 variant is the most interesting polymorphic locus located on the MEG3 transcript 17 .…”

“…Evidence of the association of MEG3 genetic variants with CRC risk was unraveled in previous research 17 , 49 , 50 . The MEG3 rs7158663 variant is the most interesting polymorphic locus located on the MEG3 transcript 17 . Interestingly, this rs7158663 polymorphism was associated with CRC risk and serum MEG3 expression in Egyptian patients 50 .…”

Novel genetic variants in long non-coding RNA MEG3 are associated with the risk of asthma

“…MEG3 SNPs are associated with multiple diseases including asthma, inflammatory response, diabetes, stroke, and cancer ( Wallace et al, 2010 ; Han et al, 2018 ; Ghaedi et al, 2018 ; Ghafouri-Fard & Taheri, 2019 ; Gao et al, 2021 ; Zhu et al, 2021 ; Zhong et al, 2022 ). Pleiotropy ( i.e., shared genetic predisposition loci to different human diseases and traits) is pervasive in human genome ( Sivakumaran et al, 2011 ; Pickrell et al, 2016 ; Tian et al, 2022 ).…”

“…We selected four SNPs ( Fig. 2 ) that were either correlated with MEG3 expression or associated with other diseases in previous publications ( Han et al, 2018 ; Ghaedi et al, 2018 ; Ghafouri-Fard & Taheri, 2019 ; Gao et al, 2021 ; Zhu et al, 2021 ; Zhong et al, 2022 ). The MEG3 rs7158663 , rs3087918 , rs11160608 , and rs4081134 genotypes were determined using TaqMan assay with an ABI 7500 Real-Time PCR System (Applied Biosystems, Foster City, CA, USA) as previously described ( Pei et al, 2022 ).…”

“…Given that aberrant MEG3 expression is linked to asthma development, we hypothesize that genetic variants that affect MEG3 expression may be associated with the risk of developing asthma. Several SNPs in MEG3 have been reported in literature that may affect MEG3 expression and influence the risks of various diseases including inflammatory response, diabetes, stroke, and cancer ( Wallace et al, 2010 ; Han et al, 2018 ; Ghaedi et al, 2018 ; Ghafouri-Fard & Taheri, 2019 ; Gao et al, 2021 ; Zhu et al, 2021 ; Zhong et al, 2022 ). We therefore perform the first study to evaluate the associations of SNPs in MEG3 with the risks of asthma using a case control study design.…”