Matias F Martinez1,2, Enzo Alveal1, Tomas G Soto1,3, Eva I Bustamante4, Fernanda Ávila5, Shrikant I Bangdiwala6,7, Ivonne Flores4, Claudia Benavides4, Ricardo Morales4, Nelson M Varela1,2, Luis A Quiñones1,2. 1. Laboratory of Chemical Carcinogenesis and Pharmacogenetics (CQF), Department of Basic and Clinical Oncology (DOBC), Faculty of Medicine, University of Chile, Santiago, Chile. 2. Latin American Network for the Implementation and Validation of Pharmacogenomic Clinical Guidelines (RELIVAF-CYTED), Madrid, Spain. 3. Departamento De Ciencias Básicas Santiago, Facultad De Ciencias, Universidad Santo Tomás, Santiago, Chile. 4. Cancer Institute Arturo López Pérez Foundation, Santiago, Chile. 5. Infectology Section, Medicine Department, Clinical Hospital of the University of Chile, Santiago, Chile. 6. Population Health Research Institute, McMaster University, Hamilton, ON, Canada. 7. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
Abstract
PURPOSE: Neutropenia is a common event in patients undergoing cytotoxic chemotherapy for the treatment of a hematological malignancy. Some polymorphisms, as IL-6 -572C>G (rs1800796), IL-1β -31 G>A (rs1143627), and CARD8 304T>A (rs2043211), in genes related to the inflammatory process, could affect the level of absolute neutrophil count (ANC) after chemotherapy. Since an efficient inflammatory process enhances neutrophil survival, we hypothesize that these polymorphisms are associated with ANC. PATIENTS AND METHODS: We carried out a prospective cohort study in two hospitals in Santiago, Chile. The patients included were adults diagnosed with acute myeloblastic leukemia, acute lymphoblastic leukemia, or non-Hodgkin's lymphoma, undergoing cytotoxic chemotherapy. We use a multilevel linear regression model to test our hypothesis. The best model was selected using the Akaike's information criterion (AIC). RESULTS: We analyzed 1726 hemograms and ANCs from 172 hospitalizations from 32 patients. The results show that CC and CG genotypes of IL-6 -572 C>G polymorphism are associated with higher ANCs compared with the GG genotype (Ln (ANC) ~ 0.81 IC95% 0.02-1.55). Similarly, TT and AT genotypes of CARD8 304T>A polymorphism were related to higher ANCs compared with AA (Ln (ANC) ~ 0.95 IC95% 0.02-1.82). IL-1β genetic polymorphism had no statistically significant association with ANC. CONCLUSION: IL-6 rs1800796 -572C>G and CARD8 rs2043211 304T>A polymorphisms are associated with the absolute neutrophil count in patients undergoing cytotoxic chemotherapy for treatment of hematological malignancies. Our findings might be useful to improve the safety of chemotherapy through predictive ANC models.
PURPOSE: Neutropenia is a common event in patients undergoing cytotoxic chemotherapy for the treatment of a hematological malignancy. Some polymorphisms, as IL-6 -572C>G (rs1800796), IL-1β -31 G>A (rs1143627), and CARD8 304T>A (rs2043211), in genes related to the inflammatory process, could affect the level of absolute neutrophil count (ANC) after chemotherapy. Since an efficient inflammatory process enhances neutrophil survival, we hypothesize that these polymorphisms are associated with ANC. PATIENTS AND METHODS: We carried out a prospective cohort study in two hospitals in Santiago, Chile. The patients included were adults diagnosed with acute myeloblastic leukemia, acute lymphoblastic leukemia, or non-Hodgkin's lymphoma, undergoing cytotoxic chemotherapy. We use a multilevel linear regression model to test our hypothesis. The best model was selected using the Akaike's information criterion (AIC). RESULTS: We analyzed 1726 hemograms and ANCs from 172 hospitalizations from 32 patients. The results show that CC and CG genotypes of IL-6 -572 C>G polymorphism are associated with higher ANCs compared with the GG genotype (Ln (ANC) ~ 0.81 IC95% 0.02-1.55). Similarly, TT and AT genotypes of CARD8 304T>A polymorphism were related to higher ANCs compared with AA (Ln (ANC) ~ 0.95 IC95% 0.02-1.82). IL-1β genetic polymorphism had no statistically significant association with ANC. CONCLUSION: IL-6 rs1800796 -572C>G and CARD8 rs2043211 304T>A polymorphisms are associated with the absolute neutrophil count in patients undergoing cytotoxic chemotherapy for treatment of hematological malignancies. Our findings might be useful to improve the safety of chemotherapy through predictive ANC models.
Authors: Andrew N Wilkinson; Kate H Gartlan; Greg Kelly; Luke D Samson; Stuart D Olver; Judy Avery; Nienke Zomerdijk; Siok-Keen Tey; Jason S Lee; Slavica Vuckovic; Geoffrey R Hill Journal: J Immunol Date: 2018-04-06 Impact factor: 5.422
Authors: Randy A Taplitz; Erin B Kennedy; Eric J Bow; Jennie Crews; Charise Gleason; Douglas K Hawley; Amelia A Langston; Loretta J Nastoupil; Michelle Rajotte; Kenneth Rolston; Lynne Strasfeld; Christopher R Flowers Journal: J Clin Oncol Date: 2018-02-20 Impact factor: 44.544