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). Conclusion: 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.

adult, aged, article, cancer patient, colorectal cancer, disease severity, female, genetic polymorphism, genotype, histopathology, human, hypothesis, liver venoocclusive disease, major clinical study, male, metastatic colorectal cancer, polymerase chain reaction, priority journal, risk assessment, semi nested polymerase chain reaction, treatment outcome,
British Journal of Cancer
Erasmus MC: University Medical Center Rotterdam

Vreuls, C.P.H, Olde Damink, S.W.M, Koek, G.H, Winstanley, A, Wisse, E, Cloots, R.H.E, … Driessen, A. (2013). Glutathione S-transferase M1-null genotype as risk factor for SOS in oxaliplatin-treated patients with metastatic colorectal cancer. British Journal of Cancer, 108(3), 676–680. doi:10.1038/bjc.2012.590