Clinical significance of a single nucleotide polymorphism and allelic imbalance of matrix metalloproteinase-1 promoter region in prostate cancer.
Matrix metalloproteinase-1 (MMP-1) is associated with cancer invasion and metastasis. The 2G allele of the polymorphic site in the MMP-1 promoter was demonstrated to have a higher transcription activity than the 1G allele. Allelic imbalance (AI) at 11q22 harboring the MMP-1 is frequently observed in various cancers and may be associated with an advanced disease. We conducted a case-control study to determine the association of the MMP-1 genotype with susceptibility to prostate cancer involving 283 prostate cancer patients and 251 controls. Furthermore, AI, retention allele of the MMP-1 promoter, and MMP-1 protein expression were analyzed in 77 prostate cancer specimens. The MMP-1 promoter polymorphism was associated with neither susceptibility nor progression of prostate cancer. Tumors with 1G/2G and 2G/2G genotypes had a significantly higher MMP-1 expression level compared to those with 1G/1G genotype (P=0.006 and 0.013, respectively). AI at 11q22 was observed in 13 (40.6%) of 32 informative cases. Retention of the 1G and 2G alleles were observed in 4 and 9 cases, respectively. AI was significantly associated with the Gleason score (P=0.003) and pathological stage (P=0.022). In addition, retention of the 2G allele showed a significant association with the pathological stage (P=0.026). AI at 11q22 region, retention of the 2G allele, specifically appeared to be involved in the progression of prostate cancer. However, the presence of the 2G allele of the MMP-1 promoter polymorphism itself seems to influence neither the susceptibility nor the progression of prostate cancer.
Tsuchiya
Norihiko
N
Department of Urology, Akita University School of Medicine, Akita 010-8543, Japan. tsuchiya@med.akita-u.ac.jp
Narita
Shintaro
S
Kumazawa
Teruaki
T
Inoue
Takamitsu
T
Ma
Zhiyong
Z
Tsuruta
Hiroshi
H
Saito
Mitsuru
M
Horikawa
Yohei
Y
Yuasa
Takeshi
T
Satoh
Shigeru
S
Ogawa
Osamu
O
Habuchi
Tomonori
T
D000368:Aged; D022981:Allelic Imbalance; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology
D020781:Matrix Metalloproteinase 1