Chou An-Kuo, Hsiao Chieh-Lun, Shih Tzu-Ching, Wang Hwei-Chung, Tsai Chia-Wen, Chang Wen-Shin, Liu Liang-Chih, Way Tzong-DER, Chung Jing-Gung, Bau DA-Tian
Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan, R.O.C.
Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
Anticancer Res. 2017 Sep;37(9):4973-4977. doi: 10.21873/anticanres.11908.
BACKGROUND/AIM: The matrix metalloproteinase (MMP) family of enzymes are in charge of degradation of various components of the extracellular matrix and their functional genetic polymorphisms may be associated with cancer susceptibility. The functional polymorphisms in the promoter region of MMP7 (A-181G and C-153T) have been reported to influence the binding capacity of nuclear proteins and may contribute to genetic susceptibility to cancer. In this study, we focused on investigating the contribution of the genotypes of MMP7 (A-181G and C-153T) to breast cancer in Taiwan.
These two polymorphisms were genotyped in 1,232 patients with breast cancer and 1,232 controls by polymerase chain reaction-restriction fragment length polymorphism methodology.
The odds ratios (ORs) after adjusting for age, family history of cancer, smoking and alcohol drinking status for those carrying AG and GG genotypes at MMP7 promoter A-181G were 1.22 (95%CI=0.91-1.63, p=0.2235) and 2.84 (95%CI=1.64-7.48, p=0.0007) respectively, compared to those carrying the wild-type AA genotype. Supporting this finding, the adjusted OR for those carrying the G allele at MMP7 promoter A-181G was 1.57 (95%CI=1.29-1.93, p=0.0008), compared to those carrying the wild-type A allele. There was no polymorphic genotype at MMP7 C-153T found among any of the investigated individuals.
Our findings suggest that the MMP7 A-181G polymorphisms may play a role in determining personal cancer susceptibility and GG genotype at MMP7 A-181G may serve as a biomarker for early detection and prediction of breast cancer in Taiwanese.
背景/目的:基质金属蛋白酶(MMP)家族的酶负责细胞外基质各种成分的降解,其功能性基因多态性可能与癌症易感性相关。据报道,MMP7启动子区域的功能性多态性(A-181G和C-153T)会影响核蛋白的结合能力,并可能导致癌症的遗传易感性。在本研究中,我们着重调查MMP7(A-181G和C-153T)基因型对台湾地区乳腺癌的影响。
采用聚合酶链反应-限制性片段长度多态性方法,对1232例乳腺癌患者和1232例对照者进行这两种多态性的基因分型。
在MMP7启动子A-181G位点,调整年龄、癌症家族史、吸烟和饮酒状况后,携带AG和GG基因型者的优势比(OR)分别为1.22(95%可信区间=0.91-1.63,p=0.2235)和2.84(95%可信区间=1.64-7.48,p=0.0007),而携带野生型AA基因型者。支持这一发现的是,在MMP7启动子A-181G位点携带G等位基因者的调整后OR为1.57(95%可信区间=1.29-1.93,p=0.0008),而携带野生型A等位基因者。在所有被调查个体中,未发现MMP7 C-153T位点的多态基因型。
我们的研究结果表明,MMP7 A-181G多态性可能在决定个体癌症易感性方面发挥作用,MMP7 A-181G位点的GG基因型可能作为台湾地区乳腺癌早期检测和预测的生物标志物。