基質金屬蛋白酶-8之基因型在中台灣與腎細胞癌風險的關聯

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外科; 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國防醫學院臨床醫學研究所; ⁵中國醫藥大學附設醫院泌尿部

The Linkage of Matrix Metalloproteinase 8 Genotypes on Renal Cell Carcinoma Risks 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 Center, Taipei, Taiwan, R.O.C.;

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

Purpose: Renal cell carcinoma (RCC) presents a formidable clinical challenge due to its aggressive behavior and limited therapeutic options. Matrix metalloproteinase-8 (MMP-8) has recently emerged as a potential biomarker and therapeutic target for various cancers. However, the genetic involvement of MMP-8 in RCC has remained largely obscure. This study aims to elucidate the role of MMP-8 genotypes in RCC susceptibility.

Materials and Methods: The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was employed to scrutinize the genotypes of MMP-8 C-799T (rs11225395), Val436Ala (rs34009635), and Lys460Thr (rs35866072) among 118 RCC patients and 590 controls. Furthermore, potential associations between MMP-8 genotypes and age, gender, smoking, alcohol consumption, hypertension, diabetes, and family history status in relation to RCC risk were assessed.

Results: No significant disparities in the distribution of MMP-8 rs11225395, rs34009635, and rs35866072 genotypes were observed between the RCC case and control cohorts (p>0.05). Individuals with CT and TT genotypes at MMP-8 rs11225395 exhibited 0.86- and 0.80-fold RCC risks, respectively (OR=0.57-1.31 and 0.42-1.55, p=0.5585 and 0.6228, respectively). Intriguingly, hypertensive individuals carrying the MMP-8 rs11225395 CT or TT genotype demonstrated an elevated risk for RCC compared to those with wild-type CC genotype (p=0.0440). No interactions of MMP-8 genotypes with age, gender, smoking, alcohol consumption, or diabetes status were evident (all p>0.05). No significant association was discerned for MMP-8 rs34009635 or rs35866072 genotypes.

Conclusions: MMP-8 genotypes appear to have a modest influence on individual susceptibility to RCC. Hypertensive patients with the CT or TT MMP-8 rs11225395 genotype may have an elevated risk of RCC.