Abstract
Published data on the association between 8q24 rs6983267 polymorphism and cancer risk are inconsistent. Thus, we conducted a meta-analysis to evaluate the relationship between rs6983267 polymorphism and cancer risk. We searched on PubMed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) up to November 1, 2016 for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of this association. We included 78 case-control studies with a total of 73,996 cases and 96,741 controls in this meta-analysis. The pooled results showed that rs6983267 polymorphism was significantly associated with increased risk of overall cancer in all genetic models (dominant model: OR = 1.19, 95% CI = 1.13–1.26; recessive model: OR = 1.19, 95% CI = 1.14–1.25; homozygous model: OR= 1.31, 95% CI = 1.23–1.40; heterozygous model: OR = 1.14, 95% CI = 1.10–1.19; allelic model: OR = 1.14, 95% CI = 1.11–1.18). Stratified analyses indicated that rs6983267 significantly increased the risk of colorectal cancer in Caucasians, prostate cancer in Caucasians and Asians, thyroid cancer in Caucasians and lung cancer in Asians. When studies were stratified by study quality, source of controls and genotyping method, significant associations were especially found in the high quality studies, the publication-based studies, the hospital-based studies, and the PCR-RFLP studies. Additional well-designed studies with large samples should be performed to validate our results.
Highlights
Cancer has become a major public health problem
It has been reported that the 8q24 region www.impactjournals.com/oncotarget contains multiple enhancer elements which can activate transcription of the nearby oncogene MYC; 8q24 contains several other genes that functionally participate in cancer development, including ectonucleotide pyrophosphatase/phosphodiesterase 2 gene (ENPP2) and nephroblastoma overexpressed gene (NOV)
We excluded 12 articles that did not have completely extractable data [22,23,24,25,26,27,28,29,30,31,32,33], 3 articles were excluded because they did not conform to Hardy-Weinberg Equilibrium (HWE) [34,35,36], 2 studies were excluded because they were duplicated with previous publications [37, 38]
Summary
Cancer has become a major public health problem. According to the GLOBOCAN 2012, approximately 14.1 million new cancer cases and 8.2 million cancer deaths were reported worldwide [1]. It is supposed that POU5F1P1 can encode a functional protein which contributes to carcinogenesis by acting as a weak transcriptional activator [3]; MYC, which acts as a transcriptional activator involving cell growth, differentiation, apoptosis, and other intracellular responses, is significantly associated with 8q24 [4, 5]. It has been reported that the 8q24 region www.impactjournals.com/oncotarget contains multiple enhancer elements which can activate transcription of the nearby oncogene MYC; 8q24 contains several other genes that functionally participate in cancer development, including ectonucleotide pyrophosphatase/phosphodiesterase 2 gene (ENPP2) and nephroblastoma overexpressed gene (NOV). NOV encodes regulatory protein CCN3, which involves in cancer development [6]. MetaCore regulatory network analysis found that both NOV and ENPP2 were indirectly linked by MYC [7]
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