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A meta-analysis of the association between steroid 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*

1 Cancer Research Laboratory, Fudan University Shanghai Cancer Center, Shanghai,

China, 2 Department of Oncology, Shanghai Medical College, Fudan University,

Shanghai, China, 3 Department of Urology, Fudan University Shanghai Cancer Center,

Shanghai, China, 4 Department of Medical Oncology, Fudan University Shanghai

Cancer Center, 5 Department of Epidemiology, The University of Texas MD Anderson

Cancer Center, Houston, Texas, USA

*Corresponding authors’ e-mails: dwye .shca @ gmail .com and weiqingyi@ yahoo .com

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 Fudan University.

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 V89L and A49T polymorphism and prostate cancer susceptibility are inconclusive.  Hypothesis statement SRD5A2 V89L and A49T polymorphism are associated with prostate cancer susceptibility  Description of study outcomes cancer susceptibility  Type of exposure or SRD5A2 V89L and A49T polymorphisms intervention used  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 PubMed from 1995 –Jan 2012 period included in the EMBASE from 1995 –Jan 2012 synthesis and keywords “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 PubMed, and EMBASE searched  Search software used, name We did not employ a search software. and version, including special features  Use of hand searching We hand-searched bibliographies of retrieved papers for additional references  List of citations located and Details of the literature search process are outlined in the those excluded, including flow chart. The citation list is available upon request justifications  Method of addressing articles Only two papers were excluded because the full-text was published in languages other not published in English. than English  Method of handling abstracts We had contacted a few colleagues for unpublished data and unpublished studies or studies on the association.  Description of any contact with We contacted authors who detailed information. authors Reporting of methods should include  Description of relevance or Detailed inclusion and exclusion criteria were described appropriateness of studies in the methods section. assembled for assessing the hypothesis to be tested  Rationale for the selection and Data extracted from each of the studies were relevant to coding of data the population characteristics, study design, and possible effect modifiers of the association.  Assessment of confounding No restricted for the analysis.  Assessment of study quality, We have assessed the study quality and performed including blinding of quality stratification. assessors; stratification or regression on possible predictors of study results  Assessment of heterogeneity Heterogeneity assumption was checked by the chi-square- based Q-test, H and I2 statistics.  Description of statistical Description of methods of meta-analysis, and assessment methods in sufficient detail to of publication bias are detailed in the methods. be replicated  Provision of appropriate tables We included the terms used for database search, 1 flow and graphics chart, 1 supplementary figure and 3 figures are available upon request. Reporting of results should include  Graph summarizing individual One forest plot and other forest plots are available upon study estimates and overall request. estimate  Table giving descriptive Table 1 information for each study included  Results of sensitivity testing Table 2 and Figure 3

 Indication of statistical 95% confidence intervals were presented with all uncertainty of findings 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 We discussed the results of subgroup analyses. included studies Reporting of conclusions should include  Consideration of alternative We discussed that potential unmeasured confounders such explanations for observed as gene–gene and gene–environment interactions may results have caused residual confounding.

 Generalization of the there was no overall association between V89L and conclusions 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 Fudan University.