Fang Shumei, Jin Xia, Wang Rui, Li Yan, Guo Wei, Wang Na, Wang Yimin, Wen Denggui, Wei Lizhen, Zhang Jianhui
Hebei Cancer Institute, Hebei Medical University, Shijiazhuang 050011, Hebei Province, China.
Carcinogenesis. 2005 Feb;26(2):481-6. doi: 10.1093/carcin/bgh327. Epub 2004 Nov 4.
Matrix metalloproteinases (MMPs) are proteolytic enzymes that regulate various cell behaviors in cancer biology, via their basic function of degradation of proteins. Genetic variations in several MMP promoters may influence transcription and expression of MMPs. The aim of this study is to assess the effects of the two single nucleotide polymorphisms (SNPs), the guanine insertion polymorphism in the MMP1 promoter and the adenosine insertion polymorphism in the MMP3 promoter, on risk of the development and lymphatic metastasis of non-small cell lung carcinoma (NSCLC). The MMP1 and MMP3 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 243 NSCLC patients and 350 control subjects in North China. The overall genotype and allelotype distribution of both the variants in cancer patients and controls was not significantly different (all P values are above 0.05). However, stratification analysis showed that smoking individuals with the MMP3 5A allele had a >1.5-fold increased risk to develop NSCLC, compared with those harboring the 6A homozygous [the age and gender adjusted odds ratio (OR) = 1.68, 95% confidence interval (CI) = 1.04-2.70]. In addition, the frequency of the MMP3 5A homozygote in NSCLC patients with lymphatic metastasis was significantly higher than that in lymph node negative ones (5.7 versus 0%, P = 0.04). Moreover, the MMP 1G/5A haplotype significantly increased the risk of lymphatic metastasis (OR = 3.36, 95% CI = 1.42-7.94), compared with the 2G/6A haplotype. The present result suggested that the MMP3 promoter polymorphism may modify susceptibility to NSCLC, and the MMP 1G/5A haplotype may predicate the risk of lymphatic metastasis of this tumor.
基质金属蛋白酶（MMPs）是一类蛋白水解酶，通过其降解蛋白质的基本功能，在癌症生物学中调节多种细胞行为。几种MMP启动子的基因变异可能会影响MMPs的转录和表达。本研究的目的是评估两种单核苷酸多态性（SNP），即MMP1启动子中的鸟嘌呤插入多态性和MMP3启动子中的腺苷插入多态性，对非小细胞肺癌（NSCLC）发生和淋巴转移风险的影响。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析对中国北方243例NSCLC患者和350例对照者的MMP1和MMP3 SNPs进行基因分型。癌症患者和对照者中两种变异的总体基因型和等位基因型分布无显著差异（所有P值均大于0.05）。然而，分层分析显示，与携带6A纯合子的吸烟者相比，携带MMP3 5A等位基因的吸烟个体发生NSCLC的风险增加了1.5倍以上[年龄和性别调整后的优势比（OR）=1.68，95%置信区间（CI）=1.04-2.70]。此外，发生淋巴转移的NSCLC患者中MMP3 5A纯合子的频率显著高于无淋巴结转移患者（5.7%对0%，P=0.04）。此外，与2G/6A单倍型相比，MMP 1G/5A单倍型显著增加了淋巴转移风险（OR=3.36，95%CI=1.42-7.94）。目前的结果表明，MMP3启动子多态性可能会改变对NSCLC的易感性，而MMP 1G/5A单倍型可能预示该肿瘤淋巴转移的风险。
