The association of miR‐27a rs895819 polymorphism with colorectal cancer risk in Chinese population

Abstract Background Besides environment and living habits, such as a sedentary lifestyle, smoking and drinking, genetic variation also plays an important role in the development of colorectal cancer (CRC). This study was aimed to investigate the role of miR‑27a rs895819 polymorphism on CRC risk in Chinese population. Methods In a case‐control study including 208 CRC and 312 age‐ and gender‐matched healthy control subjects, the rs895819 polymorphism was genotyped using the TaqMan allelic discrimination assay. Furthermore, a pooled analysis based on eligible studies was performed by using the STATA software. Results Logistic regression analysis showed that the rs895819 polymorphism was not associated with CRC risk. However, a pooled analysis based on five studies from Chinese population showed a statistically significant association between the rs895819 polymorphism and CRC risk (GG vs AA: OR = 1.56, 95% CI = 1.27‐1.92, Pz < .01; (AG + GG) vs AA: OR = 1.14, 95% CI = 1.01‐1.30, Pz = .04; GG vs (AG + AA): OR = 1.54, 95% CI = 1.27‐1.88, Pz < .01; G vs A: OR = 1.20, 95% CI = 1.09‐1.33, Pz < .01). Conclusion Our study suggests that miR‑27a rs895819 polymorphism plays an important role in CRC risk in Chinese population and may serve as a valuable biomarker for predicting an individual's susceptibility to CRC.

Besides environment and living habits, such as a sedentary lifestyle, smoking, and drinking, genetic variation also plays an important role in the development of CRC. 6,7 Rs895819 polymorphism is a single nucleotide polymorphism (SNP) located in the terminal loop of pre-miR-27a and has been reported to be associated with the risk of cancer, such as non-small cell lung cancer, cervical cancer, diffuse large B-cell lymphoma, and CRC. [8][9][10][11] Although several studies have suggested that the rs895819 polymorphism was associated with CRC risk in Chinese population, these results need to be further confirmed. [11][12][13] Hence, we conducted a case-control study and pooled analysis to investigate the effect of the rs895819 polymorphism on CRC risk in Chinese population. according to the manufacturer's instruction. The miR-27a rs895819 polymorphism was detected using the TaqMan allelic discrimination assay. The primer and probe sequences and reaction conditions were used according to a description of previous literature. 14 In addition, 10% samples were randomly selected to DNA sequencing.

| A case-control study
The results showed 100% concordance.

| A pooled analysis
PubMed, Embase, and CNKI databases were independently retrieved by two investigators to obtain eligible literatures on the association of rs895819 polymorphism with CRC risk in Chinese population. Flowchart of study selection was shown in Figure 1. The following search terms were used: "MIR27A or miR-27a", "rs895819 or polymorphism or variant" and "colorectal cancer or CRC". Last retrieval date was on April 2, 2020. Eligible literatures should meet all the following criteria: (a) case-control design for assessing the association of the rs895819 polymorphism with CRC risk among Chinese population; (b) detailed genotype data for calculating pooled odds ratio (OR) and 95% confidence interval (CI); (c) P value for Hardy-Weinberg equilibrium (P HWE ) in the control group > .05. The relevant data, including the first author's name, publication year, country, cancer type, genotyping method, and genotype frequency distribution of the rs895819 polymorphism in cases and controls, were extracted independently by two investigators (Table 1). In addition, two investigators independently assessed the quality of each qualified study using the quality assessment criteria. 15,16 Quality scores of each study ranged from 0 to 15. Studies with scores ≤9 were categorized into low quality, while those with scores >9 were considered as high quality. Any discrepancies would be resolved by discussion.

| Statistical analysis
In the case-control study, chi-square test and Student's t test were used to compare the gender and age distribution between cases and

| RE SULTS
In the current case-control study, there were no significant differences in the distribution of age or gender between cases and

| D ISCUSS I ON
In recent years, the role of miR-27a rs895819 polymorphism on CRC risk has been investigated in Chinese population. [11][12][13]18,19 Bian et al found that GG genotype of the rs895819 polymorphism was positively associated with an increased risk of CRC in codominant (GG vs AA) and recessive (GG vs AA/GA) models, indicating that GG genotype of the locus might increase CRC risk in Chinese population. 11 Jiang et al found that GG genotype of the rs895819 polymorphism was associated with an increased risk of CRC in Chinese population, and individuals with A allele (AA/AG) were significantly associated with a decreased risk for CRC. 12

| CON CLUS ION
Our study observed a significant association between miR-27a rs895819 polymorphism and CRC risk in Chinese population. The rs895819 polymorphism might serve as a valuable biomarker for predicting an individual's susceptibility to CRC.