The functional polymorphisms on promoter region of matrix metalloproteinase-12, -13 genes may alter the risk of epithelial ovarian carcinoma in Chinese.
OBJECTIVE
Growing evidences indicate that single nucleotide polymorphisms (SNPs) of matrix metalloproteinases (MMPs) gene promoter may alter MMPs protein expression levels to influence malignant tumors developing and progressing. Our study was to assess the effects of the SNPs in the promoter region of MMP-12 and MMP-13 on the risk of epithelial ovarian carcinoma (EOC) developing and progressing.


METHODS
MMP-12 A-82G and MMP-13 A-77G SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism in 256 EOC patients and 329 controls.


RESULTS
The A/G genotype frequency of MMP-12 was significantly higher in patients than in controls (7.0% vs 3.3%, P = 0.04); similarly, the frequency of MMP-12 82G allele was higher in patients too (P = 0.04). Compared with A/A genotype, A/G genotype significantly increased the risk of EOC (odds ratio, 2.19; 95% confidence interval, 1.01-4.72). Age-stratified analysis showed that individuals with A/G genotype had a higher risk in the final diagnosis aged younger than 50 years. We observed no overall association between MMP-13-77A/G polymorphism and EOC. However, an elevated positive association was observed for A/A versus G/G + A/G genotypes in mucinous ovarian cancer. Combining the analyzed 2 SNPs, the haplotype distributions in patients were not significantly different from that in controls.


CONCLUSIONS
These results suggested that the G allele of the MMP-12 82A/G polymorphism might be a risk factor for the development and progression of EOC and that the A/A genotype of MMP-13-77A/G polymorphism was associated with special pathological subtype and clinical stage in EOC at least in Chinese women.
Li
Yan
Y
Department of Obstetrics and Gynaecology, Hebei Medical University, Fourth Hospital, Shijiazhuang, China. Lykx1962@yahoo.com.cn
Jia
Jing-Hui
JH
Kang
Shan
S
Zhang
Xiao-Juan
XJ
Zhao
Jian
J
Wang
Na
N
Zhou
Rong-Miao
RM
Sun
Dong-Lan
DL
Duan
Ya-Nan
YN
Wang
Dong-Jie
DJ
D000328:Adult; D000368:Aged; D044466:Asian People; D005260:Female; D006801:Humans; D053508:Matrix Metalloproteinase 12 / Q000235:genetics*; D053509:Matrix Metalloproteinase 13 / Q000235:genetics*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12