Polymorphisms in the promoter regions of matrix metalloproteinases 1 and 3 and cancer risk: a meta-analysis of 50 case-control studies
Polymorphisms in the promoter regions of matrix metalloproteinases 1 and 3 and cancer risk: a meta-analysis of 50 case-control studies
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DOI：
10.1093/mutage/gep041
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发表时间：
2010-01-01
期刊：
影响因子：
2.7
通讯作者：
Yu, Long
中科院分区：
文献类型：
--
作者：
Peng, Bo;Cao, Lihuan;Yu, Long
基质金属蛋白酶（MMP）1和MMP 3是降解细胞外基质的酶，并且已经被暗示在癌症发展中起重要作用。MMP 1 - 1607 1G > 2G和MMP 3 - 1171 5A > 6A基因多态性与癌症风险的关系已被广泛研究。然而，这些研究的结果仍然是不确定的。在这里，我们对> 38000名受试者进行了荟萃分析，以更好地评估所谓的关联。对于MMP 1，发现-1607 2G/2G基因型携带者患结直肠癌的风险增加[2G/2G vs 2G/1G + 1G/1G，比值比（OR）= 1.48，95%置信区间（CI）]。（1.26-1.74），P-异质性= 0.066，I-2 = 49.3%]，头颈部癌[2G/2G vs 2G/1G + 1G/1G，OR = 1.61，95%CI（1.26-2.07），P-异质性= 0.002，I-2 = 64.7%]和肾癌[2G/2G vs 2G/1G + 1G/1G，OR = 1.82，95%CI（1.38-2.39），P-异质性= 0.589，I-2 = 0.0%]的风险。MMP 3基因-1171 5A > 6A多态性与癌症风险无相关性[6A vs 5A，OR = 1.00，95%CI（0.95-1.05），P-异质性= 0.124，I-2 = 24.9%]和个体癌症亚组，但按吸烟状况分层分析表明，在隐性遗传模式下，该多态性对吸烟者和非吸烟者的影响不同。总之，我们的研究表明，MMP 1 - 1607 2G可能与某些类型癌症的癌症风险增加有关，MMP 3 - 1171 5A > 6A可能不是癌症的主要风险因素，但它可能受到某些环境因素的影响。未来的研究需要更大的样本量来进一步评估这些关联。
Matrix metalloproteinase (MMP) 1 and MMP3 are enzymes that degrade the extracellular matrix and have been implicated to play an important role in cancer development. Many studies have been carried out on the association between polymorphisms of MMP1 -1607 1G > 2G and MMP3 -1171 5A > 6A and cancer risk. However, results from these studies remain inconclusive. Here, we performed a meta-analysis of > 38 000 subjects to better assess the purported associations. For MMP1, -1607 2G/2G genotype carriers were found to have an increased risk of colorectal cancer [2G/2G versus 2G/1G + 1G/1G, odds ratio (OR) = 1.48, 95% confidence interval (CI) (1.26-1.74), P-heterogeneity = 0.066, I-2 = 49.3%], head and neck cancer [2G/2G versus 2G/1G + 1G/1G, OR = 1.61, 95% CI (1.26-2.07), P-heterogeneity = 0.002, I-2 = 64.7%] and renal cancer [2G/2G versus 2G/1G + 1G/1G, OR = 1.82, 95% CI (1.38-2.39), P-heterogeneity = 0.589, I-2 = 0.0%] risk. For MMP3, no association was found between -1171 5A > 6A polymorphism and cancer risk in the overall group [6A versus 5A, OR = 1.00, 95% CI (0.95-1.05), P-heterogeneity = 0.124, I-2 = 24.9%] and individual cancer subgroups, but stratified analysis by smoking status showed that this polymorphism had different effects on smokers and non-smokers under recessive genetic model. In summary, our study suggests that MMP1 -1607 2G may be associated with an increased cancer risk for certain types of cancers, MMP3 -1171 5A > 6A may not be a major risk factor for cancer, but it may be modified by certain environmental factors. Future studies with larger sample sizes are warranted to further evaluate these associations in more detail.