| ObjectiveFok1(rs2228570), Bsm1(rs1544410), Taq1(rs731236), Apa1(rs7975232), Cdx2(rs11568820) and Poly A (rs17878969) were six intensively studied SNPs of vitamin Dreceptor polymorphisms both here and abroad. However, due to the heterogeneity ofpopulation, inadequate sample size of individual studies, race, intake amount and otherfactors, there are still a lot of debates on the relationship between vitamin D receptorpolymorphism and the risk of breast cancer. In order to reduce bias between studies andimprove statistical power, we have performed a meta-analysis to further clarify theassociation between Fok1, Bsm1, Taq1, Apa1, Cdx2and Poly-A polymorphisms and therisk of breast cancer.MethodsSearch strategy: we retrieved the articles using the keywords “vitamin D receptor orVDR”,“polymorphisms” and “breast cancer” from PubMed/Medline, EMBASE andChinese National Knowledge Infrastructure (CNKI) databases (search from1998to July31,2013). The languages were limited to English and Chinese.Included criteria:1) evaluation of the above variants of VDR and the risk of breastcancer,2) the use of the methodology of a case–control study,3) studies that provided thefrequencies of the variants in the cases and controls or provided sufficient data to calculatethe estimate risk for the variants,4) the confirmed histopathological diagnosis of breastcancer patients.5) If overlapping populations were identified between studies, only thelatest one was included.6) A study including two case-control groups (this was consideredas two studies in the research).Quality assessment: we used the Newcastle-Ottawa Quality Assessment Scales forcase-control studies to assess the included papers, and low-quality papers were removed. Finally, we organized and extracted relevant data reported in the literatures.Data analysis: Two investigators independently extracted the data and reached consensuson all items. STATA version10.0was selected to perform this Meta analysis.Thinkings about this meta analysis: Crude and adjusted odd ratio (OR) and95%confidence interval (CI) were pooled out to present and compare the strength of theassociations between Fok1, Bsm1, Taq1, Apa1, Cdx2and Poly-A polymorphisms andbreast cancer risk. Furthermore, if heterogeneity existed, we would perform the subgroupanalysis by different ethnicity.Results1. The included case-control studies for Fok1, Bsm1, Taq1, Apa1, Cdx2and Poly-A were17,19,20,10,4,6, respectively.2. The result of combined analyses indicated that Fok1, Bsm1, Apa1, Cdx2and Poly-Awere not statistically associated with the risk of breast cancer. In contrast, tt genotype ofTaq1was a modest risk factor for breast cancer development (tt vs. TT: OR=1.21,95%CI:1.01-1.44).3. Results from pooled adjusted ORs showed that Fok1, Apa1, Cdx2and Poly-A wereconsistent to the crude ORs. However, Bsm1and Taq1showed inconsistent results. ForTaq1, OR for tt vs. TT was1.03,95%CI:0.92-1.15, tt seemed not associated with breastcancer risk. Due to the presence of publication bias and heterogeneity between studies, wecannot confirm the relationship between Bsm1variants and breast cancer susceptibility.4. In the subgroup analyses, different genotype methods can be explained for someheterogeneity between studies, especially for Fok1and Taq1polymorphisms. However,sources of heterogeneity of other sites need to be discussed in a larger number sample size.ConclusionsThis meta-analysis suggests the roles that Fok1, Apa1, Cdx2and Poly-A polymorphismsplay in breast cancer risk were negligible, while this statement was not persistent in Bsm1and Taq1. To be conservative, we still assumed that they may play a modest role inaffecting breast cancer risk. Further studies are needed to validate our findings. |
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