Yueh Te-Cheng, Wu Cheng-Nan, Hung Yi-Wen, Chang Wen-Shin, Fu Chun-Kai, Pei Jen-Sheng, Wu Ming-Hsien, Lai Yi-Liang, Lee Yi-Min, Yen Shiou-Ting, Li Hsin-Ting, Tsai Chia-Wen, Bau DA-Tian
Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C.
Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C.
Cancer Genomics Proteomics. 2018 May-Jun;15(3):207-212. doi: 10.21873/cgp.20079.
BACKGROUND/AIM: Matrix metalloproteinases (MMPs) play important roles in inflammation and carcinogenesis, but the genotypic role of MMP-7 has never been investigated in colorectal cancer (CRC) among the Taiwanese. Therefore, in this study we aimed to evaluate the contribution of MMP-7 genotypes to the risk of CRC in Taiwan.
In this case-control study, MMP-7 A-181G and C-153T promoter genotypes were determined and their association with CRC risk were investigated among 362 CRC patients and 362 age- and gender-matched healthy controls. In addition, the interaction of MMP-7 genotypes and personal behaviors were also examined.
The percentages of variant AG and GG for MMP-7 A-181G genotypes were 10.5% and 1.7% in the CRC group and 11.9% and 2.2% in the control group, respectively (p for trend=0.7145). The allelic frequency distribution analysis showed that the variant G allele of MMP-7 A-181G conferred a slight but non-significant decreased CRC susceptibility to the wild-type C allele (odds ratio (OR)=0.86, 95% confidence interval (CI)=0.64-1.31, p=0.37). Taiwanese all harbour the CC genotype at MMP-7 C-153T. As for the gene-lifestyle interaction, there were no obvious joint effects of MMP-7 A-181G genotype on the risk of CRC among ever smoker, alcohol drinker, non-smoker or non-drinker subgroups. No statistically significant correlation was observed between MMP-7 A-181G genotypic distributions and age, gender, tumor size, location or metastasis status.
The genotypes of MMP-7 A-181G may play an indirect role in determining personal susceptibility to CRC and prognosis. The further genotyping work on MMP-7 and other genes (such as other MMPs, oncogenes and tumor suppression genes) on CRC susceptibility and prognosis, should be taken into consideration spontaneously in the precision medicine era.
背景/目的:基质金属蛋白酶(MMPs)在炎症和致癌过程中发挥重要作用,但MMP - 7的基因分型在台湾地区结直肠癌(CRC)中的作用尚未得到研究。因此,在本研究中,我们旨在评估MMP - 7基因分型对台湾地区CRC风险的影响。
在这项病例对照研究中,我们测定了362例CRC患者和362例年龄及性别匹配的健康对照者的MMP - 7 A - 181G和C - 153T启动子基因分型,并研究了它们与CRC风险的关联。此外,还研究了MMP - 7基因分型与个人行为之间的相互作用。
CRC组中MMP - 7 A - 181G基因型的变异型AG和GG百分比分别为10.5%和1.7%,对照组分别为11.9%和2.2%(趋势p = 0.7145)。等位基因频率分布分析显示,MMP - 7 A - 181G的变异型G等位基因使CRC易感性相较于野生型C等位基因略有降低,但差异无统计学意义(优势比(OR)= 0.86,95%置信区间(CI)= 0.64 - 1.31,p = 0.37)。台湾地区人群在MMP - 7 C - 153T位点均为CC基因型。至于基因 - 生活方式的相互作用,在曾经吸烟者、饮酒者、不吸烟者或不饮酒者亚组中,MMP - 7 A - 181G基因型对CRC风险均无明显的联合效应。未观察到MMP - 7 A - 181G基因分型分布与年龄、性别、肿瘤大小、位置或转移状态之间存在统计学显著相关性。
MMP - 7 A - 181G的基因型可能在决定个体对CRC的易感性和预后方面发挥间接作用。在精准医学时代,应自发考虑对MMP - 7及其他基因(如其他MMPs、癌基因和抑癌基因)进行进一步基因分型研究,以探讨其对CRC易感性和预后的影响。