MRE11、RAD50 和 NBS1 基因型對中台灣膀胱癌易感性的影響

廖丞晞^1,2,3,4 張文馨^2,3 張兆祥⁵ 蔡佳紋^2,3 包大靝^2,3,4

¹國軍臺中總醫院外科部泌尿科; ²中國醫藥大學生物醫學研究所; ³泰瑞法克斯癌症研究室; ⁴國防醫學大學臨床醫學研究所; ⁵中國醫藥大學附設醫院泌尿部

The Contribution of MRE11, RAD50, and NBS1 Genotypes to Bladder Cancer Susceptibility in mid-Taiwan

Cheng-Hsi Liao^1,2,3,4 , Wen-Shin Chang^2,3 , Chao-Hsiang Chang⁵, Chia-Wen Tsai^2,3,and Da-Tian Bau^1,2

¹ Division of Urology, Department of Surgery, Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C.;

² Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C.;

³ Terry Fox Cancer Research Laboratory;

⁴ Graduate Institute of Medical Sciences, National Defense Medical University, Taipei, Taiwan, R.O.C.;

⁵ Department of Urology, China Medical University Hospital, Taichung, Taiwan, R.O.C.;

Purpose: Genome instability is a hallmark of cancer, often accelerated by defects in DNA damage responses. MRE11‑RAD50‑NBS1 (MRN) complex plays a crucial role in sensing and repairing DNA damage; however, there is limited literature on the involvement of MRN genotypes in bladder cancer (BLCA) susceptibility. This study aimed to elucidate the impact of MRN genotypes on the risk of BLCA.   

Materials and Methods: We genotyped 14 single nucleotide polymorphisms (SNPs) in MRN genes, including rs684507, rs2155209, rs10831234, rs13447720, rs601341 in MRE11, rs17166050, rs17772583, rs6871536, rs3798134, rs2244012 in RAD50, and rs1805794, rs2735383, rs1063053, rs1063054 in NBS1, among 375 BLCA cases and 375 controls, and evaluated their contributions to BLCA susceptibility in mid-Taiwanese population.   

Results: Among these SNPs, only NBS1 rs2735383 was significantly associated with BLCA risk (p for trend=0.0053), with both CG and CC genotypes conferring higher risks (OR=1.48 and 1.95, respectively). Subgroup analysis showed that NBS1 rs2735383 was associated with BLCA risk in individuals older than 55 years (OR=2.29, p=0.0053), smokers (OR=2.56, p=0.0026), alcohol drinkers (OR=3.25, p=0.0005), and those with muscle‑invasive disease (OR=1.97, p=0.0243), but not in younger individuals, non‑smokers, non‑drinkers, or non‑muscle‑invasive cases.

Conclusions: NBS1 rs2735383 genotype may serve as a genetic biomarker for BLCA susceptibility, particularly in high risk subpopulations, including elders, smokers, drinkers, and those with muscle‑invasive disease.