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Matrix Metalloproteinase-1 and -9 Promoter Polymorphisms and Endometrial Carcinoma Risk in a Japanese Population

Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, United Kingdom

Shigeki Yoshida, MD, PhD

Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, United Kingdom; Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-Cho, Chuo-ku, Kobe, 650-0017, Japan syoshida{at}med.kobe-u.ac.jp

Stephen Kennedy, MRCOG

Masashi Deguchi, MD, PhD

Nyriyuki Ohara, MD, PhD

Takeshi Maruo, MD, PhD

Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, United Kingdom

Objective: The matrix metalloproteinases (MMPs) are a family of zinc-dependent proteases that degrade all the components of the extracellular matrix (ECM). Several studies have demonstrated association between MMP gene polymorphisms and various cancers. The object of this study was to investigate whether the MMP-1 and MMP-9 gene promoter polymorphisms are associated with endometrial carcinomas in a Japanese population.

Methods: We compared the allele frequencies and genotype distributions of each single nucleotide polymorphism in the promoter regions of MMP-1 (- 1607 1G/2G) and MMP-9 (- 1562 C/T) in 107 endometrial carcinoma cases and 213 controls using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis.

Results: The allele frequencies of MMP-1 - 1607 2G and MMP-9 - 1562T were 64.0% and 10.7% in the cases and 70.0% and 16.7% in the controls, respectively. NO significant differences in the allele frequencies or genotype distributions were found between cases and controls for the MMP-1 - 1607 1G/2G polymorphism. However, a small but significant difference in the allele frequency of the MMP-9 - 1562T allele was noted between cases and controls (P = .046; odds ratio [OR] = 1.01; 95% confidence interval [CI], 1.01 to 2.73). Stratification by histology revealed a significant difference in the frequency of the MMP-9 - 1562T allele between endometrioid carcinoma cases (10.2%) and controls (P = .043; OR = 1.76; 95% CI, 1.02 to 3.03); we did not fihd a significant difference in the frequency of the MMP-9 - 1562T allele between non-endometrioid carcinoma cases (13.2%) and controls.

Conclusion: These results suggest that the MMP-9 - 1562 C/T polymorphism may be associated with susceptibility to endometrioid carcinoma in the Japanese population.

Key Words: MMP-1 • MMP-9 • endometrial carcinoma • gene polymorphism • restriction fragment length polymorphism

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