Genetic Variations in MDM2 Gene Contribute to Renal Cell Carcinoma Susceptibility: A Genotype–Phenotype Correlation Study

Authors

Shu-Yu Chang
Wen-Shin Chang
Hou-Yu Shih
Chao-Hsiang Chang
Hsi-Chin Wu
Chia-Wen Tsai
Yun-Chi Wang
Jian Gu
Da-Tian Bau

Publication Date

1-8-2025

Journal

Cancers

Abstract

Background: This study aimed to investigate the polymorphic genotypes of MDM2 rs937282, rs937283, rs2279744, and rs769412, as well as the combined effects of MDM2 genotypes and environmental factors on RCC susceptibility.

Methods: A total of 135 RCC patients and 590 controls were recruited for MDM2 genotyping using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Quantitative PCR was performed to assess MDM2 mRNA levels among 30 healthy individuals and 22 RCC patients.

Results: MDM2 rs2279744, but not other polymorphisms, was significantly associated with an increased RCC risk (p = 0.0133). The MDM2 rs2279744 G allele was identified as a risk factor for RCC (odds ratio [OR] = 1.49, 95% confidence interval [CI] = 1.14-1.96, p = 0.0047). Among smokers (p = 0.0070), alcohol drinkers (p = 0.0233), individuals with hypertension (p = 0.0041), diabetes (p = 0.0225), and those with a family history of cancer (p = 0.0020), the MDM2 rs2279744 GT and GG genotypes exhibited increased RCC risks. However, this risk effect was not observed in non-smokers, non-drinkers, or individuals without hypertension, diabetes, or a family cancer history (all p > 0.05). Moreover, MDM2 mRNA levels were significantly higher in RCC patients compared to controls and varied among the rs2279744 genotypes, with GG genotype exhibiting the highest expression levels among both RCC patients and controls.

Conclusions: This study highlights the association between MDM2 rs2279744 genotypes and RCC risk, suggesting that genotype-associated MDM2 mRNA levels could contribute to early RCC detection. Further studies are warranted to elucidate the detailed mechanisms underlying the role of MDM2 in RCC development.

Keywords

genotype, MDM2, phenotype, renal cell carcinoma, single nucleotide polymorphism (SNP), Taiwan

DOI

10.3390/cancers17020177

PMID

39857959

PMCID

PMC11763691

PubMedCentral® Posted Date

1-8-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes