Matrix metalloproteinase 1 gene polymorphism as a prognostic predictor of invasive cervical cancer.
OBJECTIVE
Whereas human papillomavirus (HPV) infection is the major determinant of cervical carcinogenesis, host genetic factors may confer individual susceptibility and prognosis. Matrix metalloproteinase 1 (MMP-1) is an important modulator of carcinogenesis. A guanine insertion (2G) polymorphism at nucleotide -1607 of the MMP-1 gene promoter creates an Ets-1-binding site, which increases transcription activity. The present study investigates the association between MMP-1 polymorphism and cervical neoplasia, and their prognostic significance.


METHODS
In this study, the MMP-1 polymorphism was assessed in 135 high-grade squamous intraepithelial lesions (HSILs) and 197 invasive squamous cell carcinomas (SCCs), and in age-matched controls, by capillary electrophoresis. The association of clinicopathological factors and HPV status with MMP-1 genotypes was tested.


RESULTS
Frequencies of the 2G allele in HSIL and SCC were 64% and 65%, respectively, which did not differ significantly from control values (66% and 64%, respectively). The 2G allele was associated with advanced stages of disease (P = 0.03), whereas the G allele was more common in patients with regional lymph node metastases (P = 0.02). The survival time in patients with the heterozygous genotype G/2G (median, 55.3 months) was significantly longer than those with either the G/G (50.3 months) or 2G/2G genotype (43.9 months) (P = 0.02). No significant correlation between HPV status and MMP-1 genotype was identified.


CONCLUSIONS
The genetic polymorphisms of MMP-1 are not associated with the risk of HSIL and SCC, but with the invasiveness and prognosis of SCC. The heterozygous genotype of MMP-1 can be used as a prognostic marker in patients with invasive cervical cancer.
Lai
Hung-Cheng
HC
Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taipei, 325, Sec. 2 Cheng-Gung Road, Taipei 114, Taiwan, ROC.
Chu
Chi-Ming
CM
Lin
Ya-Wen
YW
Chang
Cheng-Chang
CC
Nieh
Shin
S
Yu
Mu-Hsien
MH
Chu
Tang-Yuan
TY
D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008207:Lymphatic Metastasis; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications; D011110:Polymorphism, Genetic; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000821:virology
D020781:Matrix Metalloproteinase 1