CyclinD1 and interleukin-1 receptor antagonist polymorphisms are associated with prognosis in neoadjuvant-treated gastric carcinoma.

Stocker, G; Ott, K; Henningsen, N; Becker, K; Hapfelmeier, A; Lordick, F; Hois, S; Plaschke, S; Höfler, H; Keller, G

doi:10.1016/j.ejca.2009.09.021

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Title:: CyclinD1 and interleukin-1 receptor antagonist polymorphisms are associated with prognosis in neoadjuvant-treated gastric carcinoma.
Document type:: Journal Article
Author(s):: Stocker, G; Ott, K; Henningsen, N; Becker, K; Hapfelmeier, A; Lordick, F; Hois, S; Plaschke, S; Höfler, H; Keller, G
Abstract:: PURPOSE: We evaluated DNA polymorphisms in genes related to DNA repair, cell-cycle control and tumour microenvironment to determine possible associations with response and survival in neoadjuvant-treated gastric cancer patients. PATIENTS AND METHODS: One hundred and seventy eight patients who received platinum/5FU-based chemotherapy were genotyped for 10 polymorphisms in nine genes (ERCC1: Asn118Asn, C>T; ERCC1: 8092C>A; TP53: Arg72Pro, GA; STK15: Phe31Ile, A>T; VEGF: 936C>T; TNF-alpha: -308G>A; interleukin-1b (IL-1B): -511C>T; IL-1 receptor antagonist (IL-1RN): variable tandem repeat; IL-8: -251T>A). Genotypes were correlated with histopathological and clinical response and overall (OS) and progression-free survival (PFS). RESULTS: Only the cyclinD1 genotypes were associated with clinical response ( [Formula: see text] ). Significantly worse survival rates were noted in patients homozygous for the G-allele as compared to patients with the AG or AA genotypes of the cyclinD1 polymorphism (OS: P(log-rank)=0.024; PFS: P(log-rank)=0.007) and in patients homozygous for the short allele compared to all other genotypes at the IL-1RN polymorphic locus (OS: P(log-rank)=0.026; PFS: P(log-rank)=0.013). The combination of both unfavourable genotypes demonstrated strong prognostic relevance (OS: P(log-rank)=0.006; PFS: P(log-rank)=0.001). Multivariate analysis for OS in the group of completely resected patients (n=139) revealed statistical significance for ypM (P<0.001), histopathological response (P<0.001) and the combined cyclinD1/IL-1RN genotypes (P=0.043). CONCLUSION: The cyclinD1 and IL-1RN polymorphisms were associated with survival. The combination of specific cyclinD1 and IL-1RN genotypes showed a particular prognostic relevance and should be considered an independent prognostic marker for neoadjuvant-treated gastric cancer patients.
Journal title abbreviation:: Eur J Cancer
Year:: 2009
Journal volume:: 45
Journal issue:: 18
Pages contribution:: 3326-35
Language:: eng
Fulltext / DOI:: doi:10.1016/j.ejca.2009.09.021
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/19822419
Print-ISSN:: 0959-8049
TUM Institution:: Institut für Allgemeine Pathologie und Pathologische Anatomie; Institut für Medizinische Statistik und Epidemiologie
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