title: A deletion polymorphism in glutathione-S-transferase mu (GSTM1) and/or theta (GSTT1) is associated with an increased risk of toxicity after autologous blood and marrow transplantation.
abstract: Toxicity after blood and marrow transplantation (BMT) has interindividual variability that may be explained by common genetic polymorphisms in critical pathways. The glutathione-S-transferase (GST) isoenzymes detoxify the reactive oxygen species generated by chemotherapy agents and radiation. We investigated whether deletion polymorphisms in 2 GST genes (GSTM1 and GSTT1) were associated with toxicity after autologous or allogeneic BMT. The study population was selected from 699 consecutive BMT patients from 2 centers in Buffalo, NY, and Moscow, Russia, of whom 321 (203 autologous, 118 allogeneic BMT) had available banked samples and amplifiable DNA. Fifty percent of patients were homozygous null for GSTM1, which did not vary by center; however, the GSTT1 homozygous null deletion polymorphism occurred more frequently in patients treated in Moscow (38% versus 18%, P < .001). Overall grade 2-4 regimen-related toxicity occurred in 56%, with nearly 1 in 5 patients having 2 or more organ systems affected. Among autologous BMT patients, a deletion polymorphism in 1 or both genes was significantly associated with increased occurrence of overall toxicity (71% versus 56%, P = .034) and mucositis (74% versus 55%, P = .006). GSTM1 and/or GSTT1 deletion polymorphisms were not associated with toxicity after allogeneic BMT. Future studies may allow for individualized genetic risk stratification.
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. theresa.hahn@roswellpark.org
authors.forename: Theresa
authors.initials: T
authors.lastname: Hahn
authors.forename: Eugenia
authors.initials: E
authors.lastname: Zhelnova
authors.forename: Lara
authors.initials: L
authors.lastname: Sucheston
authors.forename: Irina
authors.initials: I
authors.lastname: Demidova
authors.forename: Valery
authors.initials: V
authors.lastname: Savchenko
authors.forename: Minoo
authors.initials: M
authors.lastname: Battiwalla
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Smiley
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
authors.forename: Philip L
authors.initials: PL
authors.lastname: McCarthy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002648:Child; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics*; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D019337:Hematologic Neoplasms / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D009031:Moscow; D009518:New York; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D011110:Polymorphism, Genetic / Q000235:genetics*; D044469:Racial Groups; D011832:Radiation Injuries / Q000235:genetics*; D012306:Risk; D012307:Risk Factors; D017384:Sequence Deletion / Q000235:genetics; D016019:Survival Analysis; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation / Q000009:adverse effects; D055815:Young Adult
chemical_list: D005982:Glutathione Transferase; C413545:glutathione S-transferase T1