Association of a haplotype of matrix metalloproteinase (MMP)-1 and MMP-3 polymorphisms with renal cell carcinoma.
It has been shown that the matrix metalloproteinase (MMP)-1 promoter polymorphism 1G/2G is associated with an increased risk of developing various cancers including renal cell carcinoma (RCC), and is in linkage disequilibrium (LD) with the MMP-3 promoter polymorphism 5A/6A. These two genes are localized in 11q22 adjacent to each other. However, the relationship between the MMP-3 5A/6A polymorphism and susceptibility to cancer remains ambiguous. In this study, we genotyped eight polymorphisms in the region containing the MMP-1 and MMP-3 genes in 177 healthy subjects, and explored the relationships between RCC and these polymorphisms or haplotypes in 156 RCC cases and 230 age- and gender-matched controls. All the subjects studied were of Japanese descent. There were three polymorphisms that showed stronger LD with the MMP-1 1G/2G promoter variant than with the MMP-3 5A/6A promoter variant. One of these three polymorphisms was present in exon 2 of the MMP-3 gene and caused an amino acid change, Glu45Lys (G/A). When the genotype distribution of Glu45Lys was compared between RCC patients and controls, the frequency of the G/G genotype was significantly higher in the patients [age- and gender-adjusted odds ratio (OR) = 1.81, 95% confidence interval (CI) = 1.20-2.74]. A significant increase in the frequency of the 2G/2G genotype of the MMP-1 1G/2G polymorphism was also observed in the patients (age- and gender-adjusted OR = 1.86, CI = 1.23-2.82), whereas there was no significant difference for the MMP-3 5A/6A polymorphism. As expected based on these genotype-level results, the frequency of the 2G-G haplotype of MMP-1 1G/2G and MMP-3 Glu45Lys (G/A) polymorphisms was significantly higher in the patients than in the controls (crude OR = 1.95, CI = 1.31-2.91). These findings suggest that this haplotype of MMP-1 and MMP-3 variants may be associated with the risk of developing RCC.
Department of Urology, Yamaguchi University School of Medicine, Yamaguchi, Japan.
Hiroshi
H
Hirata
Naoko
N
Okayama
Katsusuke
K
Naito
Ryo
R
Inoue
Satoru
S
Yoshihiro
Hideyasu
H
Matsuyama
Yutaka
Y
Suehiro
Yuichiro
Y
Hamanaka
Yuji
Y
Hinoda
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors
D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1