Catherine Van Poznak1, Evan L Reynolds2, Cherry L Estilo3, Mimi Hu4, Bryan Paul Schneider5, Daniel L Hertz6, Christina Gersch1, Jacklyn Thibert7, Dafydd Thomas8, Mousumi Banerjee2, James M Rae1, Daniel F Hayes1. 1. Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. 2. School of Public Health, University of Michigan, Ann Arbor, MI, USA. 3. Dental Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 4. Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 5. Divisions of Hematology/Oncology and Clinical Pharmacology, Department of Medicine with a Secondary Appointment in the Department of Medical and Molecular Genetics, Indiana University, Bloomington, IN, USA. 6. Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA. 7. Department of Surgery, University of Michigan, Ann Arbor, MI, USA. 8. Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Abstract
BACKGROUND: A case-control study was performed to define clinical and genetic risk factors associated with osteonecrosis of the jaw in patients with metastatic cancer treated with bisphosphonates. METHODS: Clinical data and tissues were collected from patients treated with bisphosphonates for metastatic bone disease who were diagnosed with osteonecrosis of the jaw (cases) and matched controls. Clinical data included patient, behavioral, disease, and treatment information. Genetic polymorphisms in CYP2C8 (rs1934951) and other candidate genes were genotyped. Odds ratios from conditional logistic regression models were examined to identify clinical and genetic characteristics associated with case or control status. RESULTS: The study population consisted of 76 cases and 126 controls. In the final multivariable clinical model, patients with osteonecrosis of the jaw were less likely to have received pamidronate than zoledronic acid (odds ratio = 0.18, 95% Confidence interval: 0.03-0.97, p = .047) and more likely to have been exposed to bevacizumab (OR = 5.15, 95% CI: 1.67-15.95, p = .005). The exploratory genetic analyses suggested a protective effect for VEGFC rs2333496 and risk effects for VEGFC rs7664413 and PPARG rs1152003. CONCLUSIONS: We observed patients with ONJ were more likely to have been exposed to bevacizumab and zoledronic and identified potential genetic predictors that require validation prior to clinical translation.
BACKGROUND: A case-control study was performed to define clinical and genetic risk factors associated with osteonecrosis of the jaw in patients with metastatic cancer treated with bisphosphonates. METHODS: Clinical data and tissues were collected from patients treated with bisphosphonates for metastatic bone disease who were diagnosed with osteonecrosis of the jaw (cases) and matched controls. Clinical data included patient, behavioral, disease, and treatment information. Genetic polymorphisms in CYP2C8 (rs1934951) and other candidate genes were genotyped. Odds ratios from conditional logistic regression models were examined to identify clinical and genetic characteristics associated with case or control status. RESULTS: The study population consisted of 76 cases and 126 controls. In the final multivariable clinical model, patients with osteonecrosis of the jaw were less likely to have received pamidronate than zoledronic acid (odds ratio = 0.18, 95% Confidence interval: 0.03-0.97, p = .047) and more likely to have been exposed to bevacizumab (OR = 5.15, 95% CI: 1.67-15.95, p = .005). The exploratory genetic analyses suggested a protective effect for VEGFC rs2333496 and risk effects for VEGFC rs7664413 and PPARG rs1152003. CONCLUSIONS: We observed patients with ONJ were more likely to have been exposed to bevacizumab and zoledronic and identified potential genetic predictors that require validation prior to clinical translation.
Authors: Daniel L Hertz; Kelley M Kidwell; Jacklyn N Thibert; Christina Gersch; Meredith M Regan; Todd C Skaar; N Lynn Henry; Daniel F Hayes; Catherine H Van Poznak; James M Rae Journal: Mol Oncol Date: 2015-07-29 Impact factor: 6.603
Authors: Catherine Van Poznak; Mark R Somerfield; William E Barlow; J Sybil Biermann; Linda D Bosserman; Mark J Clemons; Sukhbinder K Dhesy-Thind; Melissa S Dillmon; Andrea Eisen; Elizabeth S Frank; Reshma Jagsi; Rachel Jimenez; Richard L Theriault; Theodore A Vandenberg; Gary C Yee; Beverly Moy Journal: J Clin Oncol Date: 2017-10-16 Impact factor: 44.544
Authors: P G Arduino; E Menegatti; M Scoletta; C Battaglio; M Mozzati; A Chiecchio; D Berardi; A M Vandone; M Donadio; S Gandolfo; C Scully; R Broccoletti Journal: J Oral Pathol Med Date: 2011-01-20 Impact factor: 4.253
Authors: Jeanny B Aragon-Ching; Yang-Min Ning; Clara C Chen; Lea Latham; Jean-Pierre Guadagnini; James L Gulley; Philip M Arlen; John J Wright; Howard Parnes; William D Figg; William L Dahut Journal: Cancer Invest Date: 2009-02 Impact factor: 2.176
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