TY - JOUR
T1 - CyclinD1 and interleukin-1 receptor antagonist polymorphisms are associated with prognosis in neoadjuvant-treated gastric carcinoma
AU - Stocker, Gertraud
AU - Ott, Katja
AU - Henningsen, Nils
AU - Becker, Karen
AU - Hapfelmeier, Alexander
AU - Lordick, Florian
AU - Hois, Stefan
AU - Plaschke, Susanne
AU - Höfler, Heinz
AU - Keller, Gisela
PY - 2009/12
Y1 - 2009/12
N2 - 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, G < C; cyclinD1: Pro241Pro, G > A; STK15: Phe31Ile, A > T; VEGF: 936C > T; TNF-α: -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 (Pχ2 = 0.044). 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: Plog-rank = 0.024; PFS: Plog-rank = 0.007) and in patients homozygous for the short allele compared to all other genotypes at the IL-1RN polymorphic locus (OS: Plog-rank = 0.026; PFS: Plog-rank = 0.013). The combination of both unfavourable genotypes demonstrated strong prognostic relevance (OS: Plog-rank = 0.006; PFS: Plog-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.
AB - 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, G < C; cyclinD1: Pro241Pro, G > A; STK15: Phe31Ile, A > T; VEGF: 936C > T; TNF-α: -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 (Pχ2 = 0.044). 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: Plog-rank = 0.024; PFS: Plog-rank = 0.007) and in patients homozygous for the short allele compared to all other genotypes at the IL-1RN polymorphic locus (OS: Plog-rank = 0.026; PFS: Plog-rank = 0.013). The combination of both unfavourable genotypes demonstrated strong prognostic relevance (OS: Plog-rank = 0.006; PFS: Plog-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.
KW - CyclinD1
KW - Gastric cancer
KW - Interleukin
KW - Neoadjuvant chemotherapy
KW - Prognosis
UR - http://www.scopus.com/inward/record.url?scp=70450200548&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2009.09.021
DO - 10.1016/j.ejca.2009.09.021
M3 - Article
C2 - 19822419
AN - SCOPUS:70450200548
SN - 0959-8049
VL - 45
SP - 3326
EP - 3335
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 18
ER -