Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia.
Slager SL., Skibola CF., Di Bernardo MC., Conde L., Broderick P., McDonnell SK., Goldin LR., Croft N., Holroyd A., Harris S., Riby J., Serie DJ., Kay NE., Call TG., Bracci PM., Halperin E., Lanasa MC., Cunningham JM., Leis JF., Morrison VA., Spector LG., Vachon CM., Shanafelt TD., Strom SS., Camp NJ., Weinberg JB., Matutes E., Caporaso NE., Wade R., Dyer MJ., Dearden C., Cerhan JR., Catovsky D., Houlston RS.
We performed a meta-analysis of 3 genome-wide association studies to identify additional common variants influencing chronic lymphocytic leukemia (CLL) risk. The discovery phase was composed of genome-wide association study data from 1121 cases and 3745 controls. Replication analysis was performed in 861 cases and 2033 controls. We identified a novel CLL risk locus at 6p21.33 (rs210142; intronic to the BAK1 gene, BCL2 antagonist killer 1; P = 9.47 × 10(-16)). A strong relationship between risk genotype and reduced BAK1 expression was shown in lymphoblastoid cell lines. This finding provides additional support for polygenic inheritance to CLL and provides further insight into the biologic basis of disease development.