Submitted April 2, 2008
Accepted May 28, 2008
Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: a genome-wide single nucleotide polymorphism analysis
Maria E Sarasquete, Ramon Garcia-Sanz*, Luis Marin, Miguel Alcoceba, Maria C Chillon, Ana Balanzategui, Carlos Santamaria, Laura Rosinol, Javier de la Rubia, Miguel T Hernandez, Inmaculada Garcia-Navarro, Juan J Lahuerta, Marcos Gonzalez, and Jesus F. San Miguel
Department of Haematology, Molecular Biology and HLA Unit, University Hospital of Salamanca, Salamanca, Spain
Centro de Investigacion del Cancer (CIC) de Salamanca, IBMCC (USAL-CSIC), Spain
Groupo Espanol De Mieloma GEM/PETHEMA, PETHEMA Foundation, Salamanca, Spain
* Corresponding author; email: rgarcias{at}usal.es.
We 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 two 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=1.07x10-6,p=4.231x10-6, p=6.22x10-6 and p=2.15x10-5, respectively). SNP rs1934951 was significantly associated with a higher risk of ONJ development even after Bonferroni correction (P corrected value=0.02). Genotyping results displayed an overrepresentation of the T allele in cases as 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 to 43.5).
