Effect of IL-1β and TNF-α polymorphisms on the prognosis and survival of gastric cancer patients

• Published in: Clinical and experimental medicine 2011-12, Vol.11 (4), p.211-217
• Main Authors: Tahara, Tomomitsu, Shibata, Tomoyuki, Nakamura, Masakatsu, Yamashita, Hiromi, Yoshioka, Daisuke, Okubo, Masaaki, Yonemura, Joh, Maeda, Yoshiteru, Maruyama, Naoko, Kamano, Toshiaki, Kamiya, Yoshio, Fujita, Hiroshi, Nakagawa, Yoshihito, Nagasaka, Mitsuo, Iwata, Masami, Hirata, Ichiro, Arisawa, Tomiyasu
• Format: Article
• Language: English
• Subjects: Aged; Female; Gene Frequency; Genetic Association Studies; Genotype; Hematology; Humans; Interleukin-1beta - genetics; Interleukin-1beta - immunology; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original Article; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Prognosis; Stomach Neoplasms - genetics; Stomach Neoplasms - immunology; Stomach Neoplasms - mortality; Survival Analysis; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology
• ISSN: 1591-8890; 1591-9528
• DOI: 10.1007/s10238-010-0129-y

So far, a number of association studies have focused on the effect of polymorphisms in IL-1β and TNF-α genes on the susceptibility to gastric cancer (GC). Here, we evaluate the possible association between common polymorphisms in the IL-1β and TNF-α genes with various clinicopathological characteristics, including overall survival of GC patients. Restriction fragment length polymorphism analysis was performed for IL-1β-31(T > C) and IL-1β-511(C > T) and TNF-α-857 (C > T) polymorphisms in 130 GC patients. IL-1β-31CC and IL-1β-511TT genotypes held a significantly lower risk of lymphatic invasion (IL-1β-31CC vs . others: adjusted OR = 0.39, 95% CI = 0.15–0.96, P  = 0.04, IL-1β-511TT vs . others: adjusted OR = 0.23, 95% CI = 0.08–0.67, P  = 0.007). The IL-1β-31CC and IL-1β-511TT genotypes were weakly associated with reduced risk of venous invasion (IL-1β-31CC vs . others: adjusted OR = 0.35, 95% CI = 0.12–1.05, P  = 0.06, IL-1β-511TT vs . others: adjusted OR = 0.32, 95% CI = 0.08–1.20, P  = 0.09). The IL-1β-511TT genotype was also weakly associated with reduced risk of lymph node metastasis (IL-1β-511TT vs . others: adjusted OR = 0.42, 95% CI = 0.17–1.04, P  = 0.06). When the TNF-α-857CT and TNF-α-857-TT genotypes were considered as T carrier, the patients with TNF-α-857T carrier showed significantly better overall survival than patients with CC genotype ( P  = 0.011). GC patients who have both IL-1β-31 CC and IL-1β-511 TT genotypes and have at least one of protective genotypes (IL-1β-31 CC, IL-1β-511 TT, TNF-α-857 T carrier) were also associated with better prognostic factors, such as lymphatic and venous invasion better survival. IL-1β-31CC, IL-1β-511TT genotype, and TNF-α-857T carrier may have protective effect against GC progression.