Carcinogenesis Advance Access published online on August 19, 2004
Carcinogenesis, doi:10.1093/carcin/bgh269
© 2004 by Oxford University Press
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1 Hebei Cancer Institute, Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
* To whom correspondence should be addressed. E-mail: Jianhuizh{at}hotmail.com.
The matrix metalloproteinases (MMPs), a family of proteolytic enzymes that degrade different components of extracellular matrix, play important roles in tumor development and invasion. A single adenine insertion/deletion polymorphism (6A/5A) in the MMP3 promoter region causes transcriptional elevation. The aim of this study is to assess the effects of this single nucleotide polymorphism (SNP) on the development and clinical staging of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA). The MMP3 SNP was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 417 cancer patients (234 ESCC and 183 GCA) and 350 controls in North China. The overall distribution of the MMP3 SNP in ESCC and GCA patients was not significantly different from that in healthy controls. However, smoking individuals with the 5A/5A or 5A/6A genotype in ESCC patients were significantly more common than in controls (37.5% versus 23.3%,
Revised July 19, 2004
Accepted August 10, 2004
CARCINOGENESIS
The functional SNP in the matrix metalloproteinase-3 promoter modifies susceptibility and lymphatic metastases in esophageal squamous cell carcinoma but not in gastric cardiac adenocarcinoma
2 The Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
Abstract 
2 = 5.13, P = 0.02). Thus, smokers with at least one 5A allele significantly increased the risk to ESCC, compared with those with the 6A homozygote (age and sex adjusted OR = 1.95, 95% CI = 1.08-3.53). The significant difference in the SNP distribution between ESCC, GCA patients and controls was not observed when stratified by family history of upper gastrointestinal cancer. In addition, the frequency of the 5A/5A+5A/6A genotypes in ESCC patients with and without lymphatic metastasis was significantly different (45.8% versus 27.8%, 2 = 4.56, P = 0.03). Therefore, patients with at least one 5A allele significantly increased the prone of lymphatic metastasis in ESCC. In contrast, the significant difference in the SNP distribution between patients with and without lymphatic metastasis was not observed in GCA. The present study suggested that the MMP3 promoter SNP might be associated with risk of development and lymphatic metastasis in ESCC but not in GCA.
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