Prognostic role of interleukin-1beta gene and interleukin-1 receptor antagonist gene polymorphisms in patients with advanced gastric cancer.
OBJECTIVE
A high interleukin-1beta (IL-1B) and interleukin-1 receptor antagonist (IL-RN) ratio underlies an unfavorable proinflammatory status. Also, it seems to be involved in the mechanisms of cancer cachexia and tumor angiogenesis and metastasis. Two single nucleotide polymorphisms in IL-1B gene (IL-1B-511C/T,IL-1B-31T/C) and a variable number of tandem repeat polymorphisms in IL-RN gene (IL-1RNlong/2) enhance the circulating levels of the two cytokines. The prognostic role of IL-1B/IL-1RN genotypes was investigated in patients with relapsed and metastatic gastric cancer treated with palliative chemotherapy.


METHODS
Before starting palliative chemotherapy, 123 prospectively enrolled patients supplied peripheral-blood samples for DNA extraction. Survival data were analyzed according to IL-1RN/IL-1B genotypes.


RESULTS
Forty-two patients showed wild-type genotypes (IL-1RNlong/long, IL-1B-511C/C, and IL-1B-31T/T; group A). Forty-five patients showed the IL-1RN2 polymorphism, with wild-type IL-1B genotypes in seven patients and with IL-1B-511C/T and/or IL-1B-31T/C polymorphisms in 38 patients (group B). The remaining 36 patients demonstrated wild-type IL-1RN, with IL-1B-511C/T and/or IL-1B-31T/C polymorphisms (group C). In group A and B patients, the median progression-free survival (PFS) was 25 and 26 weeks, respectively, and median overall survival (OS) was 42 and 43 weeks, respectively. Group C patients showed worse PFS (median, 16 weeks) and OS (median, 28 weeks) than group A (P = .006 for PFS; P = .0001 for OS) and group B patients (P = .01 for PFS; P = .0001 for OS). The long/T/C haplotype was overrepresented in patients with shortened PFS (P = .001) and OS (P = .0005).


CONCLUSIONS
In patients with advanced gastric cancer, IL-1B polymorphisms showed adverse prognostic influence when coupled with wild-type IL-1RN genotype. These findings deserve further investigation for potential anticancer activity of recombinant IL-RN.
Graziano
Francesco
F
Medical Oncology Unit, Hospital of Urbino, via Bonconte da Montefeltro, 61029, Urbino, Italy. frada@tin.it
Ruzzo
Annamaria
A
Santini
Daniele
D
Humar
Bostjan
B
Tonini
Giuseppe
G
Catalano
Vincenzo
V
Berardi
Rossana
R
Pizzagalli
Francesca
F
Arduini
Federica
F
Bearzi
Italo
I
Scartozzi
Mario
M
Cascinu
Stefano
S
Testa
Enrica
E
Ficarelli
Rita
R
Magnani
Mauro
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005838:Genotype; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010166:Palliative Care; D011110:Polymorphism, Genetic; D011379:Prognosis; D011446:Prospective Studies; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D016019:Survival Analysis
D007375:Interleukin-1; D017472:Receptors, Interleukin-1