Clear cell renal cell carcinoma (ccRCC) is the predominant subtype of renal tumor with unpredictable course and clinical outcome, accounting for about 2% of all malignant neoplasms. There is a need to develop new diagnostic and prognostic markers of the disease [1].
Single nucleotide polymorphisms (SNPs) are powerful tools for studying biological processes (>1%) and genetic architecture of diseases. SNPs are often localized in non-coding regions of the genome, including long non-coding RNAs (lncRNAs). The lncRNAs are transcripts longer than 200 nucleotides and lack the ability to encode proteins. It has been reported that lncRNAs play a key role in the regulation of gene expression and are involved in the pathogenesis of ccRCC [1].
The aim is to search for risk markers for the development of ccRCC based on the analysis of polymorphic variants in the genes of long non-coding RNAs.

The material for the study was 128 DNA samples of patients with ccRCC, Tatars by ethnicity and 134 healthy individuals. Genotyping was performed by TaqMan method.

The frequency of the rs11263432*C allele in LINC02952/LINC02953 genes in the group of patients with ccRCC amounted to 30.5%, rs11263432*T - 69.5%, in control: rs11263432*C - 39.2%, rs11263432*T - 60.8%. Thus rs11263432*T allele is risky (OR=2.32 (95%CI=1.1-5.3) p=0.04), rs11263432*C is a protective marker for ccRCC (OR=0.43 (95%CI=0.2-0.9) p=0.04). When analyzing rs4506680 in LINC02747/LINC02952 genes, no statistically significant results were found, but there was a trend towards an increased frequency of the rs4506680*T allele in the control group, which did not reach statistical significance, probably due to the small sample size. We also showed an association of the rs793096*T allele with the risk of developing ccRCC (OR=1.49 (95%CI=1.0-2.1) p=0.03), and the rs793096*C allele with a decreased risk of developing ccRCC (OR=0.67 (95%CI=0.5-1.0) p=0.03).

According to our data, rs11263432*T and rs793096*T alleles are risky (OR=2.32 (95%CI=1.1-5.3) p=0.04 and OR=1.49 (95%CI=1.0-2.1) p=0.035, respectively) with respect to the development of ccRCC. Similar results were reported in the GWAS study of renal cancer by Mark Perdue et al. which revealed their prognostic significance for ccRCC [2].
We did not find statistically significant associations of risk of ccRCC with rs4506680*T, which may be due to the small sample size. In a study [3], rs4506680*T was shown to be a risk marker for ccRCC. LINC02747 lncRNA is known to be highly expressed in ccRCC tissues and suppresses miR-608, a known oncosuppressor of ccRCC cells. The expression level of LINC02747 has been shown to be stage-dependent in ccRCC and negatively correlated with miR-608 expression. As a result of miR-608 suppression, the expression of TFE3 gene increases, and its hyperexpression may lead to the formation of chimeric oncogenes caused by translocations of chromosome Xp11.2 [3].

According to the results of the association analysis of polymorphic variants rs11263432, rs4506680, rs793096 in LINC02952, LINC02953, LINC02747, LINC02664 genes in patients with ccRCC and in controls, we can assume that polymorphic variants may be significant for predicting the development of ccRCC.

Gayyed MF, Soliman MM, El-Hussieny M. Clinical utility of MCM2 and CD44 expression in clear cell renal cell carcinoma. Pol J Pathol. 2020;71(4):339-346.
Purdue MP, Dutta D, Machiela MJ et al. Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions. Nat Genet. 2024 Apr 26;56:809–818.
Ju X, Sun Y, Zhang F, et al. Long Non-Coding RNA LINC02747 Promotes the Proliferation of Clear Cell Renal Cell Carcinoma by Inhibiting miR-608 and Activating TFE3. Front Oncol. 2020 Dec 23;10:573789.