# Effect of HVEM/CD160 Variations on the Clear Cell Renal Carcinoma Risk and Overall Survival

## TL;DR

This study shows that genetic variations in HVEM and CD160 genes are linked to increased risk and survival outcomes in clear cell kidney cancer.

## Contribution

The study identifies specific gene polymorphisms in HVEM and CD160 associated with ccRCC risk and survival for the first time.

## Key findings

- Heterozygosity in rs2231375 and rs2234167 increases the risk of clear cell renal carcinoma.
- In women, HVEM SNPs rs8725 and rs1886730 are also linked to higher ccRCC risk.
- The rs1886730 SNP is associated with overall survival in ccRCC patients.

## Abstract

Renal cell carcinoma (RCC) accounts for approximately 90–95% of all kidney cancers in adults, with clear cell RCC (ccRCC) being the most frequently identified subtype. RCC is known for its responsiveness to immunotherapy, making it an area of significant research interest. Immune checkpoint (IC) molecules, which regulate immune surveillance, are established therapeutic targets in RCC. The aim of this study was to analyze the influence of HVEM and CD160 gene polymorphisms on ccRCC susceptibility and patient overall survival (OS) over a ten-year period of observation. We genotyped three HVEM single nucleotide polymorphisms (SNPs): rs1886730, rs2234167, and rs8725, as well as two CD160 SNPs: rs744877 and rs2231375, in 238 ccRCC patients and 521 controls. Our findings indicated that heterozygosity within rs2231375 and/or rs2234167 increases ccRCC risk. Furthermore, in women, heterozygosity within HVEM SNPs rs8725 and rs1886730 is also associated with an increased ccRCC risk. The presence of a minor allele for rs1886730, rs2234167, rs8725, and rs2231375 was also correlated with certain clinical features of ccRCC. Moreover, rs1886730 was found to be associated with OS. In conclusion, our study highlights an association between HVEM and CD160 polymorphisms and the risk of developing ccRCC as well as OS.