Abstract
Background and ObjectivesTumor necrosis factor-alpha (TNF-a) was related to inflammation and involved in the development of colorectal cancer. Polymorphisms located in TNF-a promoter region, such as 308G/A and 238G/A, could affect the risk of various types of cancer by regulating TNF-a production. In this study, a meta-analysis was performed to investigate the association between common polymorphisms of TNF-a promoter region and colorectal cancer susceptibility.MethodsSearching of several databases was performed for all publications on the association between TNF-a polymorphisms and colorectal cancer. Summary odds ratios (ORs) with their 95% confidence intervals (95% CIs) were calculated using random-effects models. Stratified analyses based on ethnicity and control population source were also conducted.ResultsOverall, TNF-a 308A polymorphism showed a significant association with increased risk of colorectal cancer in worldwide populations under homozygote comparison [AA vs. GG, OR (95% CI) = 1.46 (1.07–1.97)] other than heterozygote comparison [AG vs. GG, OR (95% CI) = 1.05 (0.93–1.19)]. TNF-a 238A was not associated with colorectal cancer risk under homozygote or heterozygote comparisons. In stratified analysis, significant association was observed only in Western populations [AA vs. GG, OR (95% CI) = 1.39 (1.01–1.91)] other than in Eastern populations under homozygote comparison. No significant difference was observed between population-based subgroup and hospital-based subgroup.Conclusions TNF-a 308A was moderately associated with an increased risk of colorectal cancer in Western populations, and TNF-a 238A polymorphism was not significantly associated with colorectal cancer risk.
Highlights
Colorectal cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer-related death worldwide [1]
A comprehensive searching for all articles that had been published on the association between Tumor necrosis factor-alpha (TNF-a) polymorphisms and the risk of colorectal cancer was performed, using the following terms in the MEDLINE, PubMed, EMBASE: (‘Tumor Necrosis Factor-alpha’ [MeSH] odds ratios (ORs) ‘Tumor Necrosis’ OR TNF) AND (‘Polymorphism, Genetic’ [MeSH] OR polymorphism OR polymorphisms OR risk) AND
For colorectal cancer, two previous metaanalyses reported that TNF-a 308 polymorphism was not associated with colorectal cancer risk [22,23], and one of these two meta-analyses demonstrated that TNF-a 308A polymorphism was associated with reduced risk of colorectal cancer in Western population [22]
Summary
Colorectal cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer-related death worldwide [1]. Colorectal cancer is becoming an important public health problem, especially in developed countries. A number of risk factors for colorectal cancer were identified [5]. Markers of systemic inflammation, obesity, and diabetes were found to be associated with colorectal cancer risk in prospective epidemiologic studies [6]. Tumor necrosis factor-alpha (TNF-a) was related to inflammation and involved in the development of colorectal cancer. Polymorphisms located in TNF-a promoter region, such as 308G/A and 238G/A, could affect the risk of various types of cancer by regulating TNF-a production. A meta-analysis was performed to investigate the association between common polymorphisms of TNF-a promoter region and colorectal cancer susceptibility
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