Single nucleotide polymorphisms in MMP1 and MMP3 gene promoters as risk factor in head and neck squamous cell carcinoma.
Matrix metalloproteinase (MMP) 1 and 3 genes play an important role in initiating tumor growth and promoting cell spread. Since MMP1 and MMP3 transcription levels can be modulated by promoter polymorphism, we investigated the impact of different genotypes on the occurrence of head and neck cancer in a Caucasian case control study. DNA was extracted from 126 male head and neck cancer patients and from 249 male hospitalized-based controls. Genotyping was carried out using PCR multiplex allowing the co-amplification of MMAP1-1607 bp and MMP3-1171 bp polymorphisms. PCR products were separated on a capillary electrophoresis. The MMP1-2G and the MMP3-6A allele frequencies were significantly lower in cases than in controls. In particular homozygous 2G/2G individuals were at lower risk of cancer than the 1G/1G carriers (OR= 0.37 95%CI [0.19-0.71], p=0.003). MMP1 and MMP3 polymorphisms were in moderate linkage disequilibrium in cases and controls (D'=0.41 and D'=0.46). Haplotype frequencies distribution derived from these 2 polymorphisms was significantly different between cases and controls (p=0.01). The haplotype analysis suggested an implication of both MMP1 and MMP3 polymorphisms in the head and neck squamous cell carcinoma susceptibility. Indeed, the presence of the MMP1-2G and MMP3-6A alleles seemed to be associated with decreased risk of head and neck squamous cell carcinoma but mainly when they were carried by the same haplotype. By comparison to the 1G-5A haplotype, the 2G-6A haplotype was associated with a lower risk of head and neck squamous cell carcinoma (OR=0.52 95%CI [0.34-0.80], p=0.003).
U490 INSERM, Laboratoire de Toxicologie Moléculaire, 45 rue des Saints Pères, 75006 Paris, France.
Franck
F
Zinzindohoué
Hélène
H
Blons
Stéphane
S
Hans
Marie-Anne
MA
Loriot
Anne-Marie
AM
Houllier
Daniel
D
Brasnu
Ollivier
O
Laccourreye
David-Alexandre
DA
Tregouet
Isabelle
I
Stucker
Pierre
P
Laurent-Puig
D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012307:Risk Factors
D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1