A Meta-Analysis of the Association Betweensteroid 5-Alpha-Reductase Type 2 SRD5A2 V89L

A Meta-Analysis of the Association Betweensteroid 5-Alpha-Reductase Type 2 SRD5A2 V89L

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A meta-analysis of the association betweensteroid 5-alpha-reductase type 2 (SRD5A2)V89L and A49T polymorphisms and risk of sporadic prostate cancer

Qiaoxin Li1,2†, Yaozhu2,3†, Jing He1,2, Mengyun Wang1,2, Meiling Zhu1,2, Tingyan Shi1,2, Lixin Qiu2,4, Dingwei Ye2,3*, Qingyi Wei1,5*

1Cancer Research Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China,2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China, 3Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China, 4Department of Medical Oncology, Fudan University Shanghai Cancer Center,5Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas,USA

*Corresponding authors’ e-mails: and

Q.-X. Li and Y. Zhu contributed equally to this work and should be considered as co-first authors

Funding: This study was supported by the grant from “China’s Thousand Talents Program” Recruitment at FudanUniversity.

Criteria / Brief description of how the criteria were handled in the meta-analysis
Reporting of background should include
 / Problem definition / Published data on the association between SRD5A2 V89Land A49Tpolymorphism and prostate cancer susceptibility are inconclusive.
 / Hypothesis statement / SRD5A2 V89Land A49T polymorphism are associated withprostate cancer susceptibility
 / Description of study outcomes / cancer susceptibility
 / Type of exposure or intervention used / SRD5A2 V89Land A49T polymorphisms
 / Type of study designs used / We included case-control studies.
 / Study population / We placed no restriction.
Reporting of search strategy should include
 / Qualifications of searchers / The credentials of the two investigators LQX and HJ are indicated in the author list.
 / Search strategy, including time period included in the synthesis and keywords / PubMed from 1995 –Jan 2012
EMBASE from 1995 –Jan 2012
“SRD5A2”, “V89L” or “rs523349”, “A49T” or “rs9282858”, “variant” or “polymorphism” or “single nucleotide polymorphism or SNP”, “cancer” or “carcinoma” or “malignancy” and “prostate disease”
 / Databases and registries searched / PubMed, and EMBASE
 / Search software used, name and version, including special features / We did not employ a search software.
 / Use of hand searching / We hand-searched bibliographies of retrieved papers for additional references
 / List of citations located and those excluded, including justifications / Details of the literature search process are outlined in the flow chart. The citation list is available upon request
 / Method of addressing articles published in languages other than English / Only two papers were excluded because the full-textwas not publishedin English.
 / Method of handling abstracts and unpublished studies / We had contacted a few colleagues for unpublished data or studies on the association.
 / Description of any contact with authors / We contacted authors who detailed information.
Reporting of methods should include
 / Description of relevance or appropriateness of studies assembled for assessing the hypothesis to be tested / Detailed inclusion and exclusion criteria were described in the methods section.
 / Rationale for the selection and coding of data / Data extracted from each of the studies were relevant to the population characteristics, study design, and possible effect modifiers of the association.
 / Assessment of confounding / No restricted for the analysis.
 / Assessment of study quality, including blinding of quality assessors; stratification or regression on possible predictors of study results / We haveassessedthe study quality and performed stratification.
 / Assessment of heterogeneity / Heterogeneity assumption was checked by the chi-square-based Q-test, H and I2 statistics.
 / Description of statistical methods in sufficient detail to be replicated / Description of methods of meta-analysis, and assessment of publication bias are detailed in the methods.
 / Provision of appropriate tables and graphics / We included the terms used for database search, 1 flow chart,1 supplementary figureand3figuresare available upon request.
Reporting of results should include
 / Graph summarizing individual study estimates and overall estimate / One forest plot and other forest plotsare available upon request.
 / Table giving descriptive information for each study included / Table 1
 / Results of sensitivity testing / Table 2 and Figure3
 / Indication of statistical uncertainty of findings / 95% confidence intervals were presented with all summary estimates, P values and results of heterogeneity
Reporting of discussion should include
 / Quantitative assessment of bias / Begg’s funnel plot and Egger’s test were performed to access the publication bias
 / Justification for exclusion / We excluded studies that had no control group or not published in English.
 / Assessment of quality of included studies / We discussed the results of subgroup analyses.
Reporting of conclusions should include
 / Consideration of alternative explanations for observed results / We discussed that potential unmeasured confounders such as gene–gene and gene–environment interactions may have caused residual confounding.
 / Generalization of the conclusions / there was no overall association between V89L and prostate cancer risk, A49T might play a role in the etiology of prostate cancer among Caucasians.
 / Guidelines for future research / It is necessary to conduct large sample studies using homogeneous cancer patients and well matched controls. Moreover, gene–gene and gene–environment interactions should also be considered in the analysis.
 / Disclosure of funding source / This study was supported by the funding from Chinese Recruitment Program of Global Experts at FudanUniversity.