Polymorphisms in the matrix metalloproteinase-1, 3, and 9 promoters and susceptibility to adult astrocytoma in northern China.
The single nucleotide polymorphisms (SNPs) in the promoter region of matrix metalloproteinase (MMP) genes may influence tumor occurrence and progression via modifying mRNA transcription and protein expression. The study aims to explore the association of the SNPs in MMP-1, 3 and MMP-9 promoters with susceptibility to adult brain astrocytoma in northern China. Genotyping for the MMP-1 -1607 2G/1G, MMP-3 -1171 5A/6A, and MMP-9 -1562 C/T SNPs were performed by PCR-RFLP methods among 236 adult astrocytoma patients and 366 healthy controls. The results showed that the overall distribution of the MMP-1 allelotype and genotype among astrocytoma patients and healthy controls was significantly different (P = 0.002 and P < 0.001, respectively). Compared with the 2G/2G genotype, the 1G/1G genotype significantly decreased the risk of astrocytoma development (adjusted OR = 0.58, 95% CI = 0.42-0.79). The similar results were obtained when stratified by gender and age at tumor diagnosis (< or =45 or >45 years). The association between MMP-3 -1171 5A/6A or MMP-9 -1562 C/T SNPs and susceptibility to astrocytoma was not observed in this study. However, MMP-1 1G-MMP-3 6A haplotype significantly reduced the risk of astrocytoma development when using MMP-1 2G-MMP-3 6A haplotype as a reference (OR = 0.45, 95% CI = 0.29-0.67). The present study suggested that, the MMP-1 -1607 1G/1G genotype and MMP-1 1G-MMP-3 6A haplotype may play protective role in the development of adult astrocytoma in northern Chinese, whereas the MMP-3 -1171 5A/6A and MMP-9 -1562 C/T polymorphisms may not be independent factors to influence susceptibility to adult astrocytoma in this population.
Lu
Zhongqiang
Z
Department of Neurosurgery, The Second Hospital of Hebei Medical University, Hepinglu 215, 050000 Shijiazhuang, Hebei Province, China. zhongqianglu@yahoo.com.cn
Cao
Yanyan
Y
Wang
Yimin
Y
Zhang
Qingjun
Q
Zhang
Xianghong
X
Wang
Shuheng
S
Li
Yuehong
Y
Xie
Huiling
H
Jiao
Baohua
B
Zhang
Jianhui
J
D000328:Adult; D001254:Astrocytoma / Q000453:epidemiology* / Q000235:genetics*; D001932:Brain Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012306:Risk
D004273:DNA, Neoplasm; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1