title: Glutathione S-transferase M1-null genotype as risk factor for SOS in oxaliplatin-treated patients with metastatic colorectal cancer.
abstract: BACKGROUND
  Oxaliplatin is used as a neo-adjuvant therapy in hepatic colorectal carcinoma metastasis. This treatment has significant side effects, as oxaliplatin is toxic to the sinusoidal endothelial cells and can induce sinusoidal obstruction syndrome (SOS), which is related to decreased overall survival. Glutathione has an important role in the defence system, catalysed by glutathione S-transferase (GST), including two non-enzyme producing polymorphisms (GSTM1-null and GSTT1-null). We hypothesise that patients with a non-enzyme producing polymorphism have a higher risk of developing toxic injury owing to oxaliplatin.
  
  
  METHODS
  In the nontumour-bearing liver, the presence of SOS was studied histopathologically. The genotype was determined by a semi-nested PCR.
  
  
  RESULTS
  Thirty-two of the 55 (58%) patients showed SOS lesions, consisting of 27% mild, 22% moderate and 9% severe lesions. The GSTM1-null genotype was present in 25 of the 55 (46%). Multivariate analysis showed that the GSTM1-null genotype significantly correlated with the presence of (moderate-severe) SOS (P=0.026).
  
  
  CONCLUSIONS
  The GSTM1-null genotype is an independent risk factor for SOS. This finding allows us, in association with other risk factors, to conceive a potential risk profile predicting whether the patient is at risk of developing SOS, before starting oxaliplatin, and subsequently might result in adjustment of treatment.
authors.affiliation: Department of Pathology, Maastricht University Medical Centre, Maastricht, The Netherlands. celien.vreuls@mumc.nl
authors.forename: C P H
authors.initials: CP
authors.lastname: Vreuls
authors.forename: S W M
authors.initials: SW
authors.lastname: Olde Damink
authors.forename: G H
authors.initials: GH
authors.lastname: Koek
authors.forename: A
authors.initials: A
authors.lastname: Winstanley
authors.forename: E
authors.initials: E
authors.lastname: Wisse
authors.forename: R H E
authors.initials: RH
authors.lastname: Cloots
authors.forename: M A J
authors.initials: MA
authors.lastname: van den Broek
authors.forename: C H C
authors.initials: CH
authors.lastname: Dejong
authors.forename: F T
authors.initials: FT
authors.lastname: Bosman
authors.forename: A
authors.initials: A
authors.lastname: Driessen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006504:Hepatic Veno-Occlusive Disease / Q000209:etiology*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D005982:Glutathione Transferase; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C413545:glutathione S-transferase T1