A Functional Analysis of Variants Associated with Therapy-Induced Second Malignancies After Hodgkin Lymphoma Identified by a Genome-Wide Scan (original) (raw)

Blood

Abstract

3892 Survivors of Hodgkin lymphoma (HL) are susceptible to radiation-induced second malignant neoplasms (SMNs). In a genome-wide association study (GWAS) of patients treated for HL who did or did not develop SMNs, we identified and validated two SMN-associated single nucleotide polymorphisms (SNPs) at 6q21, intergenic between PRDM1 and ATG5 [rs4946728: P = 1.04×10-9, OR = 3.21 (95% CI = 2.37–6.42), and rs1040411: P = 4.24×10-8, OR = 2.43 (95% CI = 1.76–3.34)]. Recently, it was demonstrated that disease-associated SNPs are more likely to be expression quantitative trait loci (eQTLs), SNPs that regulate gene expression, than are randomly chosen SNPs matched for their population allele frequencies. Indeed, we found that the 1000 SNPs most associated with SMNs are significantly enriched for eQTLs (P = 0.01). Exploring the processes regulated by SMN-associated SNPs can inform the mechanism by which SMNs result in patients treated with radiation therapy. As an initial investigation of the...

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