Synopsis and synthesis of candidate-gene association studies in chronic lymphocytic leukemia: the CUMAGAS-CLL information system.
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://biomath.med.uth.gr). 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.
Zintzaras
Elias
E
Department of Biomathematics, University of Thessaly School of Medicine, Papakyriazi 22, Larissa41222, Greece. zintza@med.uth.gr
Kitsios
George D
GD
D016001:Confidence Intervals; D016208:Databases, Factual; D020022:Genetic Predisposition to Disease; D006801:Humans; D020407:Internet; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000453:epidemiology / Q000235:genetics*; D016017:Odds Ratio; D018570:Risk Assessment