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, G < C ; cyclinD1: Pro241Pro, G > A; STK15: Phe31Ile, A > T; VEGF: 936 C > T; TNF-α: -308 G > A; interleukin-1b (IL-1B): -511 C > T; IL-1 receptor antagonist (IL-1RN): variable tandem repeat; IL-8: -251 T > 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 ( P χ 2 = 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: 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.
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