Investigation of association between LINC00673 rs11655237 C>T and Wilms tumor susceptibility

Background Wilms tumor (WT) is the most common pediatric renal malignancy. Previous genome‐wide association studies have identified that the LINC00673 rs11655237 C>T polymorphism is associated with the risk of several types of cancer. However, few studies have investigated the association between LINC00673 rs11655237 C>T and WT susceptibility. Method We genotyped LINC00673 rs11655237 C>T in 145 patients with WT and 531 cancer‐free controls recruited from southern Chinese children. The strength of association was estimated by odds ratios (ORs) and 95% confidence intervals (CIs). Results Our study indicated that there was no significant association between LINC00673 rs11655237 C>T polymorphism and WT risk under all the tested genetic models (CT vs CC: adjusted OR = 0.94, 95% CI = 0.63‐1.40; TT vs CC: adjusted OR = 0.60, 95% CI = 0.22‐1.59; TT/CT vs CC: adjusted OR = 0.89, 95% CI = 0.61‐1.31; and TT vs CC/CT: adjusted OR = 0.61, 95% CI = 0.23‐1.61). Further stratified analysis detected no significant association, either. Conclusion In conclusion, we failed to find any association between the LINC00673 rs11655237 C>T polymorphism and WT risk. This finding needs to be verified in larger studies and other populations.

some alterations in certain genes associated with genitourinary tract development may predispose to WT. However, the molecular mechanisms for this differentiation failure in the tumor are still indefinite.
Childs et al 5 examined the impacts of variation at 2p13.3, 3q29, 7p13, and 17q25.1 on cancer susceptibility. They showed that a rs11655237C>T polymorphism was significantly associated with pancreatic cancer risk; this polymorphism is located in a gene encoding a long intergenic non-coding RNA (lincRNA) LINC00673 at 17q25.1 region. The rs11655237C>T was the most significant polymorphism in that study. In addition, it was reported that rs11655237C>T in exon 4 of LINC00673 formed a target site for miR-1231 binding, consequently restraining the LINC00673's tumor-suppressing function and reducing the susceptibility of pancreatic cancer. 6 Moreover, LINC00673 is also associated with the risk of non-small-cell lung cancer (NSCLC), gastric cancer, breast cancer, hepatocellular cancer, tongue squamous cell carcinoma, and neuroblastoma. [7][8][9][10][11][12][13][14] In total, these results suggest that LINC00673 rs11655237C>T is implicated in a broad spectrum of tumors. Nevertheless, the association between LINC00673 rs11655237 C>T polymorphism and WT susceptibility is not yet reported. So we enrolled 145 cases and 531 cancer-free controls to evaluate the impact of LINC00673 rs11655237 C>T polymorphism on WT risk.

| Genotyping
Total genomic DNA was extracted from peripheral blood leukocytes with the TIANamp Blood DNA Kit (TianGen Biotech Co.). 22 Genotyping was conducted blind to the status of the case or the control. The TaqMan real-time PCR was performed as previously described. [25][26][27] Besides, approximately 10% of the DNA samples were randomly selected and re-genotyped. The result of reproducibility was 100%.

| Statistical analysis
The differences in the demographic and genotypic information between WT cases and controls were compared using chisquared test. The association between LINC00673 rs11655237 C>T and WT susceptibility was evaluated by calculating the odds ratios (ORs) and 95% confidence intervals (CIs) with unconditional multivariate logistic regression analyses. P-values < 0.05 were considered as statistically significant. All statistical analyses were two-sided and performed using SAS software (Version 9.4; SAS Institute).

| LINC00673 rs11655237 C>T polymorphism and WT susceptibility
The demographic characteristics of participants were described in Table S1. The genotype frequencies of the LINC00673 rs11655237 C>T polymorphism in WT cases and controls are shown in Table 1.
There was no significant deviation from the Hardy-Weinberg equilibrium in the controls (P = 0.279). Besides, we found that there was no significant association under all the tested genetic models (CT

| Stratified analysis
Further stratified analysis by age, gender, and clinical stages was conducted ( Table 2). The result showed no significant genetic association between the LINC00673 rs11655237 C>T polymorphism and WT risk in the subgroups defined by age, gender, or clinical stages.

| D ISCUSS I ON
Our study firstly explored the relevance between LINC00673 rs11655237 C>T polymorphism and WT susceptibility, and the result indicated that the LINC00673 rs11655237 C>T polymorphism was not associated with WT in a southern Chinese population.
LincRNAs, as the largest subclass in the non-coding transcriptome, are non-coding transcripts longer than 200 nts. Like the miRNAs, LincRNAs also play important roles in human disorders, especially tumors, and exhibit distinct gene expression patterns in primary tumors and metastases 28,29 . LincRNAs expression is strikingly tissue-specific, when compared with coding genes. 30 In the past decades, LincRNAs are known to play key roles in the process of imprinting, metastasis, deregulation of tumor suppressors, and pseudogene pairing. 31 the statistical power. Second, as a retrospective study, selection bias and information bias were inevitable. In the end, only one polymorphism of LINC00673 was studied, and in the future, more potentially functional polymorphisms need to be explored for their association of WT risk.
In conclusion, our result indicated that there was no significant association between the LINC00673 rs11655237 C>T polymorphism and WT risk in the southern Chinese population. In the future, welldesigned prospective studies that include larger sample sizes and different ethnics should be performed to validate our findings.

ACK N OWLED G M ENTS
This study was supported by grants from the National Natural