No association of the matrix metalloproteinase 1 promoter polymorphism with susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in northern China.

AIM: To investigate association of the 2G or 1G single nucleotide polymorphism (SNP) in matrix metalloproteinase 1 (MMP1) promoter with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population of North China. METHODS: MMP1 promoter SNP was genotyped by polymerase-chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis in 417 cancer patients (234 ESCC and 183 GCA) and 350 healthy controls. RESULTS: The genotype frequencies of the MMP1 promoter SNP in healthy controls were 55.4% (2G/2G), 30% (1G/2G) and 14.6% (1G/1G), respectively. The genotype and allelotype distribution in ESCC and GCA patients was not significantly different from that in healthy controls (all P values were above 0.05). Compared with the 1G/1G genotype, neither the 2G/2G nor in combination with the 1G/2G genotype significantly modified the risk of developing ESCC and GCA, the adjusted odds ratio was 1.28 (95%CI = 0.78-2.09), 1.23 (95%CI = 0.38-2.05) in ESCC and 1.39 (95%CI = 0.80-2.41), 1.34 (95%CI = 0.74-2.40) in GCA, respectively. When stratified by smoking status and family history of upper gastrointestinal cancer, the 2G/2G genotype alone or in combination with the 1G/2G genotype also did not show any significant influence on the risk of ESCC and GCA development. In addition, influence of the MMP1 SNP on lymphatic metastasis in ESCC and GCA was also not observed. CONCLUSION: The 2G or 1G SNP in the MMP1 promoter might not modify the risk of ESCC and GCA development and might not be used as a stratification marker to predict the potential of lymphatic metastasis in these two tumor types.

[Single nucleotide polymorphism in the matrix metalloproteinases promoter is associated with susceptibility to endometriosis and adenomyosis].

OBJECTIVE: To investigate the association of the matrix metalloproteinases (MMP) 1, 3 promoter single nucleotide polymorphism (SNP) with the susceptibility to endometriosis (EM) and adenomyosis. METHODS: The SNP of the MMP-1 and MMP-3 gene promoter region was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) among 100 endometriosis patients, 80 adenomyosis patients and 150 unrelated healthy women. RESULTS: (1) The frequency of 2G allelotype of MMP-1 in the EM and adenomyosis patients (79.0% and 79.4%, respectively) was significantly different from the control (67.0%) (P < 0.01). The frequencies of 1G/1G, 1G/2G and 2G/2G genotypes of EM and adenomyosis patients were significantly different from that in healthy controls (P < 0.05). Compared with 1G/1G genotype, both 2G/2G alone and in combination with 1G/2G genotype significantly increased the risk of developing EM (adjusted odds ratio was 3.65 and 3.25, 95% CI = 1.41-9.43 and 1.29-8.23, respectively), but only 2G/2G genotype significantly enhanced the risk of developing adenomyosis. (2) The frequencies of the 5A and 6A allelotype of MMP-3 among EM (14.0% and 86.0%, respectively) and adenomyosis patients (15.6% and 83.4%, respectively) were not significantly different from healthy controls (20.3% and 79.7%, respectively) (P > 0.05). The genotype distribution of 5A/5A, 5A/6A and 6A/6A in patients was not significantly different from controls (P > 0.05). Compared with the 6A/6A genotype, neither the 5A/5A alone nor in combination with the 5A/6A genotype significantly modified the risk of developing EM and adenomyosis. (3) The distribution of haplotype (1G/6A, 2G/6A, 1G/5A and 2G/5A) frequency of MMP-1 and MMP-3 SNP was significantly different between cases and controls. Compared with the 1G/6A haplotype, 2G/6A haplotype significantly enhanced the risk of developing EM, but not significantly enhanced the risk of developing adenomyosis. CONCLUSION: Individuals with the MMP-1 2G allelotype have significantly increased risk of developing EM and adenomyosis; MMP-3 promoter SNP is not associated with susceptibility to EM and adenomyosis, 2G/6A haplotype could be used as a stratified marker for EM.

[Association of single nucleotide polymorphism in matrix metalloproteinases promoter with susceptibility to ovarian cancer].

OBJECTIVE: To investigate the association of single nucleotide polymorphism in matrix metalloproteinase (MMP)-1 and MMP-3 promoter with susceptibility to ovarian cancer. METHODS: The genotype of MMP-1 and MMP-3 gene promoter region was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 122 ovarian cancer patients (ovarian cancer group) and 151 unrelated healthy women (control group). RESULTS: The frequencies of 2G and 1G alleles in ovarian cancer group were 68.0%, 32.0% and in control group 66.9%, 33.1%, with no significant difference between the two groups (P > 0.05); the genotype frequencies of 1G/1G, 1G/2G, 2G/2G in ovarian cancer group (16.4%, 31.1% and 52.5%) was not significantly different from that in control group (16.6%, 33.1% and 50.3%) (P > 0.05). Compared to 1G/1G genotype, neither 2G/2G nor in combination with 1G/2G genotype significantly modified the risk of developing ovarian cancer. The adjusted odds ratio was 1.05 (95% CI = 0.53-2.07) and 1.00 (95% CI = 0.52-1.90), respectively. The frequencies of 5A and 6A alleles in MMP-3 in ovarian cancer group were 17.2%, 82.8% and in control group 20.2%, 79.8%, with no significant difference between the two groups (P > 0.05). No significant difference in genotype (5A/5A, 5A/6A and 6A/6A) distribution between ovarian cancer and control groups was observed, either. Compared to 6A/6A genotype, 5A/5A plus 5A/6A genotype did not significantly modify the risk of developing ovarian cancer, the adjusted odds ratio was 1.34 (95% CI = 0.81-2.23). 2G allele of MMP-1 and 6A allele of MMP-3 were in linkage disequilibrium (chi(2) = 56.53, P < 0.01). CONCLUSION: MMP-1 and MMP-3 promoter polymorphism is not associated with the susceptibility to ovarian cancer.

[Association of polymorphisms of p21cip1 and p27kip1 genes with susceptibilities of esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma].

BACKGROUND & OBJECTIVE: Researches showed that polymorphisms of p21(cip1) and p27(kip1) genes have associations with susceptibilities of breast cancer, lung cancer, prostate cancer, and so on. This study was to investigate the possible association of functional polymorphisms of p21(cip1) and p27(kip1) genes with susceptibilities of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population from a high incidence region in north China. METHODS: The single nucleotide polymorphisms (SNPs) in the 3'-untranslated region of p21(cip1) gene and in codon 109 of p27(kip1) gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 299 ESCC patients, 256 GCA patients, and 437 healthy controls from a high incidence region of north China. RESULTS: The frequency of p21(cip1) T allelotype was significantly higher in ESCC patients than in healthy controls (42.8% vs. 36.7%, P=0.02). The frequency of p27(kip1) V allelotype was significantly higher in ESCC and GCA patients than in healthy controls (96.8% and 96.1% vs. 92.9%, P=0.001, P=0.02). The distribution of p21(cip1) genotypes among ESCC patients was significantly different from that among healthy controls (P=0.04); compared with the combination of the C/C and C/T genotypes, the T/T genotype significantly elevated the risk of developing ESCC [adjusted odds ratio (OR)=1.93, 95% confidence interval (CI)=1.12-3.94]. The distribution of p27(kip1) genotypes among ESCC and GCA patients were significantly different from that among healthy controls (P=0.002, P=0.01); compared with the combination of V/G and G/G genotypes, the V/V genotype significantly elevated the risk of developing ESCC and GCA (adjusted OR=2.44, 95% CI=1.21-4.02; adjusted OR=2.01, 95% CI=1.12-3.68). When stratified for smoking and family history of upper gastrointestinal cancers (UGIC), compared with the combination of V/G and G/G genetypes, the V/V genotype significantly elevated the risk of developing both ESCC and GCA in smokers (adjusted OR=2.24, 95% CI=1.14-4.03; adjusted OR=2.61, 95% CI=1.25-3.82) and ESCC in individuals with positive family history of UGIC (adjusted OR =2.04, 95% CI=1.04-3.43). The combination of p21(cip1) T/T and p27(kip1) V/V genotypes significantly elevated the risk of developing ESCC and GCA (adjusted OR=3.78, 95% CI=1.46-5.89; adjusted OR=2.56, 95% CI=1.06-4.78). CONCLUSION: In north China, p21(cip1) polymorphisms might be correlated with the susceptibility of ESCC, p27(kip1) polymorphisms might be correlated with the susceptibilities of ESCC and GCA, and they might have synergetic effect on ESCC and GCA development.

[Correlation of matrix metalloproteinase-3 polymorphism to genetic susceptibility and lymph node metastasis of non-small cell lung cancer].

BACKGROUND & OBJECTIVE: Matrix metalloproteinases (MMPs) might be involved in invasion and metastasis of tumors by degrading extracellular matrix (ECM) and basement membrane (BM). The 5A or 6A single nucleotide polymorphism (SNP) at the -1 171 bp site of promoter region of MMP-3 may modify the transcription and local expression of MMP-3. This study was to investigate correlation of the MMP-3 SNP with genetic susceptibility and lymph node metastasis of non-small cell lung cancer (NSCLC). METHODS: Genotypes of the MMP-3 SNP of 173 NSCLC patients and 350 healthy controls were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Distributions of the MMP-3 genotypes in both NSCLC patients and healthy controls were accorded with Hardy-Weinberg equilibrium (P>0.05). Frequencies of the 6A/6A, 5A/6A, and 5A/5A genotypes were 65.3%, 30.6%, and 4.1% in NSCLC patients, and 67.7%, 30.0%, and 2.3% in healthy controls, whereas frequencies of the 6A and 5A alleles were 79.3% and 20.7% in NSCLC patients, and 82.7% and 17.3% in healthy controls. The overall genotype and allelotype distributions among NSCLC patients and healthy controls were similar (P>0.05). However, stratified analysis found that frequency of the 5A allele was significantly higher in smoking patients than in healthy smokers (21.0% vs. 12.9%, P=0.03). Therefore, smokers with the 5A/6A or 5A/5A genotype have higher risk of developing NSCLC [age and sex adjusted odds ratio (OR) =2.07, 95% confidence interval (CI) =1.13-3.78]. When stratified by pathologic types, no significant difference in MMP-3 genotype or allelotype distribution between adenocarcinoma patients, squamous carcinoma patients and healthy controls was shown. When further stratified by lymphatic metastasis status, frequencies of the 5A allele and the 5A/5A genotype were significantly higher in NSCLC patients with lymphatic metastasis than in NSCLC patients without lymphatic metastasis (22.8% vs. 11.8%, P=0.02u 8.6% vs. 0%, P=0.02). Thus, NSCLC patients with the 5A/5A genotype have higher risk of lymphatic metastasis than NSCLC patients with the 6A/6A genotype (OR=12.38, 95% CI=0.76-202.13). CONCLUSIONS: The 5A allele of MMP-3 might be associated with the increased susceptibility to NSCLC among smokers. The 5A homozygote might increase the risk of lymphatic metastasis in NSCLC patients.