Affiliation:
1. Department of Haematology, Molecular Biology, and Human Leukocyte Antigen (HLA) Unit, University Hospital of Salamanca;
2. Centro de Investigación del Cáncer (CIC) de Salamanca, Instituto de Biologia Molecular y Celular del Cancer (IBMCC; Universidad de Salamanca–Consejo Superior de Investigaciones Científicas [USAL-CSIC]); and
3. Grupo Español de Mieloma/Programa para el Estudio de la Terapéutica en Hemopatías Malignas (GEM/PETHEMA)
Abstract
AbstractWe have explored the potential role of genetics in the development of osteonecrosis of the jaw (ONJ) in multiple myeloma (MM) patients under bisphosphonate therapy. A genome-wide association study was performed using 500 568 single nucleotide polymorphisms (SNPs) in 2 series of homogeneously treated MM patients, one with ONJ (22 MM cases) and another without ONJ (65 matched MM controls). Four SNPs (rs1934951, rs1934980, rs1341162, and rs17110453) mapped within the cytochrome P450-2C gene (CYP2C8) showed a different distribution between cases and controls with statistically significant differences (P = 1.07 × 10−6, P = 4.231 × 10−6, P = 6.22 × 10−6, and P = 2.15 × 10−6, respectively). SNP rs1934951 was significantly associated with a higher risk of ONJ development even after Bonferroni correction (P corrected value = .02). Genotyping results displayed an overrepresentation of the T allele in cases compared with controls (48% vs 12%). Thus, individuals homozygous for the T allele had an increased likelihood of developing ONJ (odds ratio 12.75, 95% confidence interval 3.7-43.5).
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Cited by
196 articles.
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