Human leukocyte antigen class I alleles and the risk of chronic myelogenous leukemia: a meta-analysis

A number of different human leukocyte antigen (HLA) allele associations with chronic myelogenous leukemia (CML) have been previously reported. The specific associations reported in one population, however, are rarely replicated in other populations. We attempted to explore these associations by performing a meta-analysis of published studies. Following a Medline search, we identified four studies which presented raw data on all allele associations with CML (significant and nonsignificant). Meta-analysis of these revealed a significant risk association with the HLA-A*02 (pooled odds ratio 1.33, 95% confidence interval 1.10-1.61) allele and a significant protective effect with the HLA-B*35 allele (pooled odds ratio 0.64, 95% confidence interval 0.48-0.86). To our knowledge this is the first study to demonstrate the epidemiologic association between HLA-A*02 and the risk of CML, and we discuss this in the context of recent immunological studies reporting data on BCR-ABL fusion peptide presentation and subsequent immune response. Our findings suggest that individual epidemiological studies may lack statistical power, or may have other interfering factors which prevent the unmasking of overall associations. Meta-analyses of published studies may overcome these limitations and may prove useful in uncovering allele-disease associations.