Genetic variants in a long noncoding RNA related to Sunitinib Resistance predict risk and survival of patients with renal cell carcinoma

OBJECTIVE: LncARSR (lncRNA Activated in RCC with Sunitinib Resistance, ENST00000424980) is a newly identified lncRNA to promote the sunitinib resistance of renal cell carcinoma (RCC), which may contribute to tumorigenesis and progression. This study aimed to explore the association of lncARSR tagSNPs with the risk and prognosis of RCC. METHODS: In this study, a 2‐stage case‐control study was performed to evaluate the association between 2 tagging SNPs (rs1417080 and rs7859384) and RCC susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by unconditional logistic regression analyses. Different survival time was estimated by the Kaplan‐Meier method and compared by the Log‐rank test. Hazard ratios (HRs) and their 95% CIs were calculated to determine predictive factors by Cox proportion hazards model. RESULTS: When combing discovery and validation sets together, rs7859384 was determined to be significantly associated with the decreased RCC risk with all P < 0.05 in 4 models (co‐dominant model, additive model, dominant model and recessive model). stratified analyses showed prominent risk effect of SNP rs7859384 GA/GG genotypes was found in clinical subgroups of stage I and stage II (P = 0.009, OR = 0.77, 95% CI = 0.64‐0.94) and individuals with clear cell RCC (P = 0.014, OR = 0.79, 95% CI = 0.65‐0.95). A protective effect of SNP rs7859384 GA/GG genotypes was observed among individuals with BMI > 24 (P = 0.025, OR = 0.74, 95% CI = 0.56‐0.96), without hypertension (P = 0.037, OR = 0.79, 95% CI = 0.63‐0.99), without family history of cancer (P = 0.048, OR = 0.83, 95% CI = 0.68‐1.00). Survival analyses revealed individuals with GA/GG genotypes had higher survival rate compared with the corresponding AA wild genotypes in the dominant model (log‐rank P = 0.005, adjusted HR = 0.34, 95% CI = 0.16‐0.73). CONCLUSION: This study suggests that rs7859384 of lncARSR was associated with RCC susceptibility and may act as a prognostic biomarker for patients with RCC.