BACKGROUND: Inflammation, especially the cytokine response of the IL-1 family, has been shown to influence susceptibility to gastric cancer. In addition, several other pro-inflammatory cytokines have been demonstrated to influence metastasis and resistance to chemotherapy. Therefore, genetic variations within these genes may not only affect susceptibility but also influence the outcome of gastric cancer patients. A limited number of studies showed indeed an association of IL-1β and IL-1RN variations with survival of gastric cancer patients. However, results are inconsistent, possibly because of different patient cohorts and different therapies. METHODS: In this retrospective cohort study we genotyped 154 patients with gastric cancer for IL-1β and IL-1RN variations. Patients had undergone pathologically proven R0 resection and had received no additional adjuvant treatment. RESULTS: We show here a protective association with disease-free survival for both heterozygous genotypes, IL-1β SNP C-511T (rs16944) and IL-1RN VNTR. The combination of both heterozygous genotypes is the strongest predictor independent of UICC stage. CONCLUSION: Genetic variations in the IL-1β and IL-1RN genes influence disease progression in gastric cancer. Screening for these genetic variations might help to stratify therapies for gastric cancer patients in the future.
BACKGROUND: Inflammation, especially the cytokine response of the IL-1 family, has been shown to influence susceptibility to gastric cancer. In addition, several other pro-inflammatory cytokines have been demonstrated to influence metastasis and resistance to chemotherapy. Therefore, genetic variations within these genes may not only affect susceptibility but also influence the outcome of gastric cancerpatients. A limited number of studies showed indeed an association of IL-1β and IL-1RN variations with survival of gastric cancerpatients. However, results are inconsistent, possibly because of different patient cohorts and different therapies. METHODS: In this retrospective cohort study we genotyped 154 patients with gastric cancer for IL-1β and IL-1RN variations. Patients had undergone pathologically proven R0 resection and had received no additional adjuvant treatment. RESULTS: We show here a protective association with disease-free survival for both heterozygous genotypes, IL-1β SNP C-511T (rs16944) and IL-1RN VNTR. The combination of both heterozygous genotypes is the strongest predictor independent of UICC stage. CONCLUSION: Genetic variations in the IL-1β and IL-1RN genes influence disease progression in gastric cancer. Screening for these genetic variations might help to stratify therapies for gastric cancerpatients in the future.
Authors: M Moehler; S-E Al-Batran; T Andus; M Anthuber; J Arends; D Arnold; D Aust; P Baier; G Baretton; J Bernhardt; H Boeing; E Böhle; C Bokemeyer; J Bornschein; W Budach; E Burmester; K Caca; W A Diemer; C F Dietrich; M Ebert; A Eickhoff; C Ell; J Fahlke; H Feussner; R Fietkau; W Fischbach; W Fleig; M Flentje; H E Gabbert; P R Galle; M Geissler; I Gockel; U Graeven; L Grenacher; S Gross; J T Hartmann; M Heike; V Heinemann; B Herbst; T Herrmann; S Höcht; R D Hofheinz; H Höfler; T Höhler; A H Hölscher; M Horneber; J Hübner; J R Izbicki; R Jakobs; C Jenssen; S Kanzler; M Keller; R Kiesslich; G Klautke; J Körber; B J Krause; C Kuhn; F Kullmann; H Lang; H Link; F Lordick; K Ludwig; M Lutz; R Mahlberg; P Malfertheiner; S Merkel; H Messmann; H-J Meyer; S Mönig; P Piso; S Pistorius; R Porschen; T Rabenstein; P Reichardt; K Ridwelski; C Röcken; I Roetzer; P Rohr; W Schepp; P M Schlag; R M Schmid; H Schmidberger; W-H Schmiegel; H-J Schmoll; G Schuch; C Schuhmacher; K Schütte; W Schwenk; M Selgrad; A Sendler; J Seraphin; T Seufferlein; M Stahl; H Stein; C Stoll; M Stuschke; A Tannapfel; R Tholen; P Thuss-Patience; K Treml; U Vanhoefer; M Vieth; H Vogelsang; D Wagner; U Wedding; A Weimann; H Wilke; C Wittekind Journal: Z Gastroenterol Date: 2011-04-07 Impact factor: 2.000
Authors: Ron N Apte; Shahar Dotan; Moshe Elkabets; Malka R White; Eli Reich; Yaron Carmi; Xiaping Song; Tatyana Dvozkin; Yakov Krelin; Elena Voronov Journal: Cancer Metastasis Rev Date: 2006-09 Impact factor: 9.264
Authors: Dorthe Hellemann; Anders Larsson; Hans O Madsen; Jan Bonde; Jens Otto Jarløv; Jørgen Wiis; Torsten Faber; Jørn Wetterslev; Peter Garred Journal: Hum Mol Genet Date: 2007-09-14 Impact factor: 6.150