The miR-608 rs4919510 polymorphism may modify cancer susceptibility based on type

Abstract

Previous meta-analysis has not shown different effects of miR-608 rs4919510 polymorphism in specific cancer types and reported no significant association between rs4919510 and cancer risk among Chinese. However, more recent findings have been inconsistent. Therefore, we performed an updated meta-analysis to examine whether this polymorphism is associated with cancer risk based on ethnicity and type. A total of 18 case-control studies, comprising 12,517 cases and 15,624 controls, were included in our study. Surprisingly, in contrast with previous meta-analysis, a significant association between the rs4919510 polymorphism and cancer risk was observed in Chinese (CG vs CC: odds ratio = 1.11; 95% confidence interval = 1.04–1.19). In further stratified analyses based on cancer type, rs4919510 was significantly associated with an increased risk of papillary thyroid cancer (CG vs CC: odds ratio = 1.25; 95% confidence interval = 1.01–1.54) and exhibited borderline significant associations with increased risk of gastric cancer (GG vs CC: odds ratio = 1.27; 95% confidence interval = 1.00–1.62) and lung cancer (CG vs CC: odds ratio = 1.14; 95% confidence interval = 0.99–1.32), but a decreased risk of colorectal cancer (GG vs CC: odds ratio = 0.74; 95% confidence interval = 0.60–0.91). Moreover, the RegulomeDB database indicated that rs4919510 may affect the expression of two nearby genes ( SEMA4G and MRPL43 ), and the Cancer Genome Atlas database revealed that the expression level of SEMA4G was significantly lower in colorectal cancer and lung cancer tissues than that in adjacent non-tumour tissues, while the expression level of SEMA4G was significantly higher in gastric cancer tissues than that in adjacent non-tumour tissues. These findings provide evidence that the miR-608 rs4919510 polymorphism may modify cancer susceptibility in a type-specific manner. Furthermore, SEMA4G may function as an oncogene or tumour suppressor to regulate tumour development in a type-specific manner. Further studies with experimental evaluations are warranted.