A single nucleotide polymorphism in the matrix metalloproteinase-1 and interleukin-8 gene promoter predicts poor prognosis in tongue cancer.
OBJECTIVE
Matrix metalloproteinase-1 (MMP-1) and interleukin-8 (IL-8) play an important role in cancer development and metastasis. There is a single nucleotide polymorphism (SNP) located in the promoter region of MMP-1 and IL-8 that regulates gene expression. MMP-1 -1607 2G/2G and IL-8 -251 A/A genotypes enhance transcriptional activity and may be associated with increased risk in malignant tumors. We therefore evaluated the impact of these SNPs in tongue squamous cell carcinoma (SCC).


METHODS
In this study, we genotyped 69 tongue SCC patients. The expression of MMP-1 and IL-8 in tongue SCC patients was analyzed by immunohistochemistry.


RESULTS
We found a significant difference in IL-8 A/A genotypes with nodal recurrence (P=0.0068). An analysis of disease-free survival rates showed that the presence of both MMP-1 2G/2G and IL-8 A/A genotypes was associated with a particularly poor prognosis (P=0.0032) and was an independent prognostic factor (P=0.001). The expression of MMP-1 was significantly correlated with the frequency of MMP-1 2G/2G genotypes (P=0.049).


CONCLUSIONS
These results suggest that SNP in the promoter region of MMP-1 and IL-8 plays an important role in tumor progression and recurrence through its expression in tongue SCC.
Shimizu
Yoshinori
Y
Department of Otolaryngology, School of Medicine, Kanazawa University, Takaramachi 13-1, Ishikawa, Japan. shiden@med.kanazawa-u.ac.jp
Kondo
Satoru
S
Shirai
Akiko
A
Furukawa
Mitsuru
M
Yoshizaki
Tomokazu
T
D000368:Aged; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D007124:Immunoenzyme Techniques; D016209:Interleukin-8 / Q000235:genetics*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014059:Tongue / Q000473:pathology; D014062:Tongue Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
D016209:Interleukin-8; D020781:Matrix Metalloproteinase 1