J. J. van der Reijden

Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer

Gastric cancers express enhanced levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Single-nucleotide polymorphisms (SNPs) in MMP and TIMP genes may be associated with disease susceptibility and might also affect their antigen expression. We studied the genotype distribution and allele frequencies of SNPs of MMP-2, -7, -8 and -9 and TIMP-1 and -2 in gastric cancer patients in relation to tumour progression, patient survival and tissue antigen expression. The genotype distribution and allele frequencies were similar in gastric cancer patients and controls, except for MMP-7−181A>G. In addition, the genotype distribution of MMP-7−181A>G was associated with Helicobacter pylori status (χ2 7.8, P=0.005) and tumour-related survival of the patients. Single-nucleotide polymorphism TIMP-2303C>T correlated significantly with the WHO classification (χ2 5.9, P=0.03) and also strongly with tumour-related survival (log rank 11.74, P=0.0006). Single-nucleotide polymorphisms of MMP-2, -8, -9 and TIMP-1 were not associated with tumour-related survival. Only the gene promoter MMP-2−1306C>T polymorphism correlated significantly with the protein level within the tumours. First-order dendrogram cluster analysis combined with Cox analysis identified the MMP-7−181A>G and TIMP-2303C>T polymorphism combination to have a major impact on patients survival outcome. We conclude that MMP-related SNPs, especially MMP-7−181A>G and TIMP-2303C>T, may be helpful in identifying gastric cancer patients with a poor clinical outcome.

MMP-2 geno-phenotype is prognostic for colorectal cancer survival, whereas MMP-9 is not

The prognostic significance of single-nucleotide polymorphisms (SNPs) and tumour protein levels of MMP-2 and MMP-9 was evaluated in 215 colorectal cancer patients. Single-nucleotide polymorphism MMP-2−1306T and high MMP-2 levels were significantly associated with worse survival. Extreme tumour MMP-9 levels were associated with poor prognosis but SNP MMP-9−1562C>T was not. Tumour MMP levels were not determined by their SNP genotypes.

MMP-2 and MMP-9 in normal mucosa are independently associated with outcome of colorectal cancer patients.

Background:Upregulation of the matrix metalloproteinases MMP-2 and MMP-9 in various cancers has been associated with worse survival of the patients.Methods:We assessed MMP-2 and MMP-9 levels in normal colorectal mucosa from colorectal cancer patients in relation to the course of the disease.Results:A high protein expression of MMP-2 as well as MMP-9 in normal mucosa was found to be correlated with worse 5-year survival. The combination of both parameters was an even stronger prognostic factor. These protein levels were found not to be related to the corresponding single nucleotide polymorphisms of MMP-2 (−1306C>T) and MMP-9 (−1562C>T). Multivariate analyses indicated that the MMP-2 and MMP-9 levels in normal mucosa are prognostic for survival, independent of TNM classification.Conclusion:MMP-2 and MMP-9 levels in normal mucosa are indicative of the course of disease in colorectal cancer patients.

496 LECTIN COMPLEMENT PATHWAY GENES OF DONOR AND RECIPIENT DETERMINE THE RISK OF CLINICALLY SIGNIFICANT INFECTIONS AFTER ORTHOTOPIC LIVER TRANSPLANTATION

for protease inhibitors (PI) (I13V, L33V, M36I, K43T, L63P, I64V, A71T, V77I). None harboured non-nucleoside reverse transcriptase inhibitors (NNRTI) mutations resistance. Virological failure under raltegravir (RAL) and enfuvirtide (ENF) was linked to the selection of the Q148R mutation and the N43D mutation. Three isolates had complete or possible resistance to NRTI (Stanford algorithm). Therapeutic trough levels of IS were maintained within the therapeutic target ranges. ARV adherence was suboptimal for one patient under ENF. HIV viral load became undetectable for all patients after changing ARV.