Journal
AMERICAN JOURNAL OF EPIDEMIOLOGY
Volume 170, Issue 6, Pages 671-678Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/aje/kwp201
Keywords
database; epidemiology; genes; genome; human; information systems; leukemia; lymphocytic; chronic; B-cell; meta-analysis; polymorphism; genetic
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Funding
- Bodosakis Foundation
- University of Thessaly Resear
- ALPHA Bank
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A comprehensive and systematic assessment of the current status of candidate-gene association studies for chronic lymphocytic leukemia (CLL) was conducted. Data from 989 candidate-gene association studies (1992-2009) involving 905 distinct genetic variants were analyzed and cataloged in CUMAGAS-CLL, a Web-based information system which allows the retrieval and synthesis of data from candidate-gene association studies on CLL (http://www.w3.org/1999/). Nine genetic variants (BAX (rs4645878), GSTM1 (null/present), GSTT1 (null/present), IL10 (rs1800896), LTA (rs909253), MTHFR (rs1801131), MTHFR (rs1801133), P2RX7 (rs3751143), and TNF (rs1800629)) were investigated in 4 or more studies, and their results were meta-analyzed. In individual studies, 147 variants showed a significant association with CLL risk under any genetic model. For 53 variants, the association was significant at P < 0.01 with an increased risk greater than 40%. Only 0.3% of studies had statistical power greater than 80%. In meta-analyses, none of the variants showed significant results, and heterogeneity ranged from none to high. Large and rigorous genetic studies (candidate-gene association studies and genome-wide association studies) designed to investigate epistatic and gene-environment interactions may produce more conclusive evidence about the genetic etiology of CLL. CUMAGAS-CLL would be a useful tool for current genomic epidemiology research in the field of CLL.
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