The CCND1 c.870G>A polymorphism is a risk factor for t(11;14)(q13;q32) multiple myeloma

Abstract

A number of specific chromosomal abnormalities define the subgroups of multiple myeloma. In a meta-analysis of two genome-wide association studies of multiple myeloma including a total of 1,661 affected individuals, we investigated risk for developing a specific tumor karyotype. The t(11;14)(q13;q32) translocation in which CCND1 is placed under the control of the immunoglobulin heavy chain enhancer was strongly associated with the CCND1 c.870G>A polymorphism (P = 7.96 × 10(-11)). These results provide a model in which a constitutive genetic factor is associated with risk of a specific chromosomal translocation.

Figure 1. Regional plot of association results and recombination rates around the CCND1 locus at chromosome 11q13.

Triangles denote directly typed SNPs and circles imputed SNPs. −log₁₀ P values (y axis) of the SNPs are shown according to their chromosomal positions (x axis). The color intensity of each symbol reflects the extent of LD with rs603965, from white (r² = 0) to dark red (r² = 1.0). Genetic recombination rates, estimated using HapMap CEU samples, are shown with a light blue line. Physical positions are based on NCBI build 37 of the human genome. Genes have been redrawn to show their relative positions; therefore, maps are not to physical scale.