TNF-α-308 G>A polymorphism and colorectal cancer risk: a meta-analysis

Abstract

Dear Editor: Recently, TNF-α-308 G>A polymorphism has been found relating to many kinds of carcinomas. But previous studies show different ideas about the relationship between TNF-α308 G>A polymorphism and colorectal cancer (CRC) risk. Although similar meta-analysis has been published before, no significant association between TNF-α-308 G>A and CRC risk was observed. With a series of new studies published, we performed an updated meta-analysis to estimate the effect of the TNF-α-308 G>A polymorphism on CRC risk. Firstly, we used the keywords and search terms “TNF-α308,” “polymorphism,” and “colorectal cancer” to look for potential studies on Pubmed and Embase database. There were 36 studies as a result of the search, and two of them were excluded because they were duplicates of earlier studies. And then, for some reasons, such as case only study, published before the year of 2000, and studies indicating a relationship with other cancer and not about the polymorphism of TNF-α, ten studies were excluded after records were screened and seven studies were excluded after fulltext articles were assessed. At the same time, we retrieved two studies from the reference list of seven eligible studies. Therefore, we had a total of nine eligible studies. Among these eligible studies, we had 1,708 CRC cases and 1,754 controls. All studies were case–control studies with CRC. CRC cases were confirmed histologically or pathologically in most studies. The distribution of genotypes in the controls was in agreement with Hardy–Weinberg equilibrium except one study. In addition, one of the eligible studies was published in Chinese, but the cases and controls were Caucasian. Besides, the control group in the two eligible studies contained inflammatory bowel disease (IBD) cases, which may cause a bias. In the test of heterogeneity, we used χ-based Q test and I to test the heterogeneity among the eligible studies and it showed that there was significant heterogeneity (Q test P value00.014, I060.2 %). So, we selected the randomeffects model using the DerSimonian and Laird method to do the following analysis. In the quantitative synthesis, the strength of the association between TNF-α-308 G>A and CRC risk was measured by odds ratio (OR) with 95 % confidence interval (CI). The statistical significance of the pooled OR was determined using the Z test. Overall, comparing with wild-type GG homozygote, the variant genotype AA did not increase the risk of CRC (OR01.89, 95%CI00.94–3.78). Besides, no significant association between the polymorphism and risk of CRC in the dominant model (AA/GA vs GG, OR01.26, 95%CI00.90–1.77) or recessive model (AA vs GA/GG, OR01.75, 95%CI00.94–3.23) was observed. According to the result of stratification analysis, we explored the source of heterogeneity from the subgroup analyses of European (Q test P value00.026, I058.2 %) population controls (Q test P value00.620, I00.0 %) and hospital controls (Q test P value00.002, I080.2 %). Sensitivity analyses indicated that two independent studies, whose control group contained IBD cases, were the main origin of heterogeneity. After excluding these two Zhipeng Chen and Lingjun Zhu contributed equally to this work. Z. Chen : L. Zhu : J. Zhang :X. Chen : J. Li :Y. Shu (*) Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 GuangZhou Rd, Nanjing 210029, China e-mail: yongqian_shu@126.com