[Correlations of polymorphisms in matrix metalloproteinase-3 and -7 promoters to susceptibility to brain astrocytoma].
OBJECTIVE
Matrix metalloproteinases (MMPs) are key enzymes involved in tumor development, invasion and metastasis. The single nucleotide polymorphisms (SNPs) in the promoter regions of MMP genes may influence tumor development and progression via modulating mRNA transcription and protein expression. This study was to explore the correlations of the promoter SNPs in MMP-3 and MMP-7 genes to susceptibility to brain astrocytoma.


METHODS
The genotype of MMP-3 -1171 5A/6A and MMP-7 -181A/G polymorphisms in 236 patients with brain astrocytoma and 366 healthy controls was detected by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP).


RESULTS
The allelotype and overall genotype distribution of MMP-3 SNP among the astrocytoma patients and healthy controls were similar (P>0.05). Stratified by sex, age, and histological grade, the susceptibility to brain astrocytoma among the subjects with 5A/5A and 5A/6A genotypes and the subjects with 6A/6A genotype were similar(P>0.05). The overall genotype distribution of MMP-7 SNP among the astrocytoma patients and healthy controls were significantly different (P = 0.001). Compared with the A/A genotype, both the G/G and the A/G genotypes significantly increased the susceptibility to astrocytoma [sex-and age-adjusted odds ratio (OR) = 2.77 and 1.69, 95% confidence interval (CI)=1.27-6.02 and 1.01-2.84, respectively]. Stratification analysis showed that the G/G genotype significantly increased the susceptibility to astrocytoma in men (adjusted OR = 3.24, 95% CI = 1.12-9.41) and in the individuals younger than 45 years (adjusted OR = 3.16, 95% CI = 1.09-9.16). When stratified by histological grade, the A/G genotype increased the susceptibility to grade II astrocytoma by about 2 folds (adjusted OR = 2.06, 95% CI = 1.05 - 4.05), while the G/G genotype increased the susceptibility to grade II-IV astrocytoma by about 3 folds.


CONCLUSIONS
MMP-7 -181A/G polymorphism may influence the susceptibility to astrocytoma, while MMP-3-1171 5A/6A polymorphism has no correlation to the susceptibility.
Lu
Zhong-Qiang
ZQ
Department of Neurosurgery, The Second Affiliated Hospital, Hebei Medical University, Shijiazhuang, Hebei, 050000, PR China. zhongqianglu@yahoo.com.cn
Wang
Yi-Min
YM
Cao
Yan-Yan
YY
Zhang
Qing-Jun
QJ
Zhang
Xiang-Hong
XH
Li
Yue-Hong
YH
Wang
Heng-Shu
HS
Xie
Hui-Ling
HL
Jiao
Bao-Hua
BH
Zhang
Jian-Hui
JH
D000328:Adult; D000368:Aged; D000483:Alleles; D001254:Astrocytoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D016001:Confidence Intervals; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D055815:Young Adult
C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7