Variations in the interleukin-1 receptor antagonist gene impact on survival of patients with advanced colorectal cancer.
The interleukin-1 receptor antagonist (IL-1RA) cytokine is thought to counteract tumor angiogenesis/metastasis. Two single nucleotide polymorphisms in the IL-1RA gene (rs4251961 T/C and rs579543 C/T) influence IL-1RA circulating levels with highest production in carriers of the homozygous rs4251961 T/T and rs579543 T/T genotypes. A total of 180 patients with metastatic colorectal cancer were categorized as high IL-1RA producers if they were carriers of at least one of the rs4251961 T/T or rs579543 T/T genotypes (T/T carriers). Median survival times were 35.8 months (95% confidence interval: 29.7-43.7 months) and 28.6 months (95% confidence interval: 25.6-30 months) in 56 T/T carriers and in 124 non-T/T carriers, respectively. The favorable association between T/T carriers' status and survival was significant in the multivariate analysis (P=0.018). Also, T/T carriers and non-T/T carriers were prevalent among patients with Karnofsky performance status 90-100 and 70-80, respectively (P=0.002). These findings encourage additional studies in this field and the evaluation of a recombinant-IL-1RA for anticancer activity.
Graziano
F
F
Medical Oncology Unit, Hospital of Pesaro, Pesaro, Italy. frada@tin.it
Ruzzo
A
A
Canestrari
E
E
Loupakis
F
F
Santini
D
D
Rulli
E
E
Humar
B
B
Galluccio
N
N
Bisonni
R
R
Floriani
I
I
Maltese
P
P
Falcone
A
A
Tonini
G
G
Catalano
V
V
Fontana
A
A
Giustini
L
L
Masi
G
G
Vincenzi
B
B
Alessandroni
P
P
Magnani
M
M
D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood / Q000235:genetics*; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D020641:Polymorphism, Single Nucleotide
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D000068818:Cetuximab