Eine Kombination von Genotypen von Cyclin-D1, Interleukin-1-beta und Interleukin-1-Rezeptorantagonist erlaubt die Prädiktion der Prognose bei lokal fortgeschrittenen neoadjuvant therapierten Adenokarzinomen des Ösophagus (AEG I)

Only 30–40 % of patients respond to chemotherapy in locally advanced AEG I. Response to chemotherapy and patient’s prognosis is likely to be predicted by tumor tissue dependent characteristics as well as by constitutional genetic factors. Therefore we investigated 5-FU (MTHFR, TS) and Cisplatin (GSTT1, GSTM1, GSTP1) related polymorphisms of patients treated with 5-FU and cisplatin based neoadjuvant chemotherapy for an association with response and survival. Polymorphisms as p53, cyclin D1; interleucin-1 beta, interleucin-1 receptor agonist, TNF-alpha, potentially involved in the pathogenesis of AEG I were included. Methods: 66 patients (3 female, 63 male; 23 G1/2, 43 G3/4; 64 resected, 51 R0; 8 ypT0, 7 ypT1, 22 ypT2, 26 ypT3, 1 ypT4; 32 ypN0, 32 ypN1; med. survival: not reached, med. follow-up: 65 Mon.) were included in the study. DNA was isolated from blood or non tumorous tissue of 66 patients with locally advanced AEG I staged uT3/4 cNany cM0. Genotypes were determined by PCR and subsequent electrophoresis in a 2 % agarose gel or by allelic discrimination TaqMan PCR. Results: There was no correlation between clinical, histopathological or metabolic reponse and the examined genotypes of all analysed genes. None of the analysed genotypes was associated with prognosis in all patients (TS: p = 0.70; MTHFR: p = 0.94; GSTM: p = 0.20; GSTT: p = 0.99; GSTP: p = 0.51; p53: p = 0.42; cyclin D1: p = 0.17; IL-1 beta: p = 0.29; IL-1 RA: p = 0.48, TNF alpha: p = 0.45). However the presence of at least one prognostic or functional favorable genotype of cyclin-D1, interleucin-1-beta and interleucin-1-receptorantagonist (AA und/oder CC und/oder 2/2) defines a group of 32 patients with improved prognosis. (p = 0.008). In multivariate analysis the combination of genotypes (p = 0.007; RR 3.78, 95 % KI 1.45–9.85) and histopathological regression (p = 0.018; RR 3.52; 95 % KI 1.24–10.0) are independent prognostic factors. Conclusion: None of the included polymorphisms was associated with response or survival. The presence of at least one favourable genotype defines pretherapeutically a group of patients with improved prognosis.