American Journal of Epidemiology Advance Access originally published online on August 21, 2009
American Journal of Epidemiology 2009 170(6):671-678; doi:10.1093/aje/kwp201
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Synopsis and Synthesis of Candidate-Gene Association Studies in Chronic Lymphocytic Leukemia: The CUMAGAS-CLL Information System
Correspondence to Dr. Elias Zintzaras, Department of Biomathematics, University of Thessaly School of Medicine, Papakyriazi 22, Larissa 41222, Greece (e-mail: zintza{at}med.uth.gr).
Received for publication December 10, 2008. Accepted for publication June 9, 2009.
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.
database; epidemiology; genes; genome, human; information systems; leukemia, lymphocytic, chronic, B-cell; meta-analysis; polymorphism, genetic
Abbreviations: BAX, BCL2-associated X protein; CI, confidence interval; CLL, chronic lymphocytic leukemia; CUMAGAS, Cumulative Meta-Analysis of Genetic Association Studies; GSTM1, glutathione S-transferase M1; GSTT1, glutathione S-transferase T1; IL10, interleukin-10; LTA, lymphotoxin alpha; MTHFR, methylenetetrahydrofolate reductase; OR, odds ratio; P2RX7, purinergic receptor P2X, ligand-gated ion channel, 7; rs, reference SNP; SLL, small lymphocytic lymphoma; SNP, single nucleotide polymorphism; TNF, tumor necrosis factor
Editor's note: This article also appears on the Web site of the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/default.htm).