Association between CHFR gene hypermethylation and gastric cancer risk: a meta-analysis

OncoTargets and Therapy, Dec 2016

Association between CHFR gene hypermethylation and gastric cancer risk: a meta-analysis Hua Shi, Xiaojing Wang, Jianbo Wang, Jundi Pan, Junwei Liu, Bin Ye Department of Gastroenterology, Lishui Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Hospital of Zhejiang University, Lishui, People’s Republic of China Background: The association between the hypermethylation of CHFR gene and gastric cancer risk has been investigated by a number of studies. However, the sample size of the majority of these studies was very small. To get a more a convincing conclusion, here we performed a meta-analysis of the previously published studies to assess the association between CHFR methylation and the risk of gastric cancer.Methods: Eligible studies were identified by searching the MEDLINE/PubMed, Embase, and Web of Science databases before May 2016 without any language restriction. The strength of the association was estimated by odds ratio with its 95% confidence interval (CI).Results: Totally 1,399 samples, including 758 gastric cancer cases and 641 controls, from 13 studies were included in the present meta-analysis. Compared with non-cancer controls, the pooled OR of CHFR methylation in gastric cancer patients was 9.08 (95% CI: 6.40–12.88, P<0.001), suggesting that the methylation of CHFR was significantly associated with increased risk of gastric cancer. Similar results were observed when subgroup analyses were performed stratified by country, ethnicity, and methylation testing methods.Conclusion: Our meta-analysis showed a strong positive correlation between CHFR methylation and risk of gastric cancer, suggesting that CHFR methylation might be a promising biomarker for the diagnosis of gastric cancer. Keywords: CHFR, methylation, tumor suppressor gene, gastric cancer, risk

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Association between CHFR gene hypermethylation and gastric cancer risk: a meta-analysis

OncoTargets and Therapy association between CHFR gene hypermethylation and gastric cancer risk: a meta-analysis 8 1 0 2 - l u J - 2 1 n o 5 0 2 . 7 . 8 6 . 1 5 y b / m o c . s s e rvepo l.yno PowerdbyTCPDF(ww.tcpdf.org) O r i g i n a l r e s e a r c h Background: The association between the hypermethylation of CHFR gene and gastric cancer risk has been investigated by a number of studies. However, the sample size of the majority of these studies was very small. To get a more a convincing conclusion, here we performed a meta-analysis of the previously published studies to assess the association between CHFR methylation and the risk of gastric cancer. Methods: Eligible studies were identified by searching the MEDLINE/PubMed, Embase, and Web of Science databases before May 2016 without any language restriction. The strength of the association was estimated by odds ratio with its 95% confidence interval (CI). Results: Totally 1,399 samples, including 758 gastric cancer cases and 641 controls, from 13 studies were included in the present meta-analysis. Compared with non-cancer controls, the pooled OR of CHFR methylation in gastric cancer patients was 9.08 (95% CI: 6.40-12.88, P,0.001), suggesting that the methylation of CHFR was significantly associated with increased risk of gastric cancer. Similar results were observed when subgroup analyses were performed stratified by country, ethnicity, and methylation testing methods. Conclusion: Our meta-analysis showed a strong positive correlation between CHFR methylation and risk of gastric cancer, suggesting that CHFR methylation might be a promising biomarker for the diagnosis of gastric cancer. - Department of gastroenterology, l ishui c entral h ospital, The Fifth a ffiliated h ospital of Wenzhou Medical University, l ishui h ospital of Zhejiang University, lishui, People’s republic of china (CR) region. The FHA and CR regions are essential for its checkpoint function, and the RF domain is required for the ubiquitin ligase activity of CHFR.9 CHFR is widely expressed in normal tissues, and loss or reduced expression of CHFR has been reported in several primary tumors. Interestingly, in cancer cell lines and several types of primary cancer, the decreased CHFR expression was reported to be caused by the hypermethylation of the CpG 810 island in the promoter region of this gene,10–12 including l-Ju2 gastric cancer.13,14 -21 Ever since the initial report of hypermethylation of 5on CHFR in gastric cancer,15 a growing number of studies have .072 investigated the association of CHFR methylation and risk ..68 of gastric cancer. However, the sample size of these studies y51 was very small; most of them enrolled less than 100 cancer /bm cases. Based on the notion that the statistical power is low .cso when there is only a small number of cases enrolled in a se case-control study, therefore, we conducted a meta-analysis rvepo l.yno of the previously published studies to assess whether there .dww lseu is an association between CHFR methylation and risk of /w an gastric cancer. / : ttsp rseo h rp Methods from oF d literature search strategy odae The MEDLINE/PubMed, Embase, and Web of Science lnw databases were used for searching literatures. The search yod was carried out before May 2016 without any language reap restriction. The keywords used for paper searching were dhT CHFR, methylation, stomach, gastric, and cancer. To search sna for additional relevant publications, the reference lists from trge relevant primary studies and review articles were also aoT checked manually. c n O study selection and data extraction We selected studies if they met all of the following criteria: 1) the study had a case-control design; 2) the study focused on the relationship between CHFR hypermethylation and risk of gastric cancer; 3) the frequency of the CHFR methylation status had been reported or could be calculated; and 4) if several studies had overlapping cancer or control cases, the studies with the largest sample size were selected in the present study. The following information were extracted, respectively, by two investigators: last name of the first author, year of the publication, country where study conducted, subject ethnicity, testing materials, numbers of cases and controls, and the method for methylation testing in each study. The two investigators reached a consensus on all items. submit your manuscript | www.dovepress.com Dovepress statistical analyses The strength of the association between CHFR methylation and gastric cancer risk was assessed by odds ratio (OR) with its 95% confidence interval (CI). The heterogeneity among the studies was estimated by a chi-square-based Q-test and further quantified by the I2 metric.16 The fixed-effects model was selected to calculate the pooled OR when the betweenstudy heterogeneity was absent.17 Otherwise, the randomeffects model was selected.18 Begg’s funnel plots and Egger’s linear regression test were used to examine whether the r (...truncated)


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Hua Shi, Xiaojing Wang, Jianbo Wang, Jundi Pan, Junwei Liu, Bin Ye. Association between CHFR gene hypermethylation and gastric cancer risk: a meta-analysis, OncoTargets and Therapy, 2016, pp. 7409-7414, DOI: 10.2147/OTT.S118070