Confirmation of involvement of new variants at CDKN2A/B in pediatric acute lymphoblastic leukemia susceptibility in the Spanish population

The locus CDKN2A/B (9p21.3), which comprises the tumor suppressors genes CDKN2A and CDKN2B and the long noncoding RNA (lncRNA) known as ANRIL (or CDKN2B-AS), was associated with childhood acute lymphoblastic leukemia (ALL) susceptibility in several genome wide association studies (GWAS). However, the variants associated in the diverse studies were different. Recently, new and independent SNPs deregulating the locus function were also identified in association with ALL risk. This diversity in the results may be explained because different variants in each population could alter CDKN2A/B locus function through diverse mechanisms. Therefore, the aim of this study was to determine whether the annotated risk variants in the CDKN2A/B locus affect the susceptibility of B cell precursor ALL (B-ALL) in our Spanish population and explore if other SNPs altering additional regulatory mechanisms could be also involved. We analyzed the four SNPs proposed by GWAs and two additional SNPs in miRNA binding sites in 217 pediatric patients with B-ALL and 330 healthy controls. The SNPs rs2811712, rs3731249, rs3217992 and rs2811709 were associated with B-ALL susceptibility in our Spanish population. ALL subtypes analyses showed that rs2811712 was associated with B-hyperdiploid ALL. These results provide evidence for the influence of genetic variants at CDKN2A/B locus with the risk of developing BALL.