Knowledge about the mechanisms underlying inter-individual differences in PONV is needed to better identify patients who are at risk of PONV. Some of the variability seen with nausea and vomiting in cancer or migraine without aura may be associated with genetic variation either in genes related to the mechanisms of nausea/vomiting or in genes related to opioid action. In cancer patients receiving opioids, the inter-individual differences in nausea and vomiting were associated with genetic markers represented by single nucleotide polymorphisms of candidates in the opioid- or nausea/vomiting signalling pathways that modulate neurotransmission by metabolising the catecholamine dopamine. A possible role has been suggested for catechol-O-methyl-transferase (COMT) which is a key modulator in the metabolism of endogenous monoaminergic neurotransmitters, and hence of opioidergic neurotransmitters. The COMT enzyme possesses a frequent non-synonymous polymorphism that encodes for the substitution of valine (Val) by methionine (Met) at codon 158 (Val158Met). The SNP rs4680 (c.472G > A) is a missense mutation leading to a four-fold reduction of the COMT enzyme. Individuals with the Val/Val genotype have the highest activity of COMT, those with the Met/Met genotype have the lowest activity of COMT, and heterozygous individuals are intermediate.11,12 Pathways involving specific neurotransmitters and their receptors are likely to be involved in PONV, for instance, dopamine, acetylcholine, histamine, cannabinoids, substance P, and 5-hydroxytryptamine. The role of dopamine is pivotal in nausea and vomiting; dopamine D2 receptor blockade, in the area postrema, has an antiemetic effect. In patients receiving COMT inhibitors, the enhanced dopaminergic activity leads dose-dependently to frequent and severe nausea and vomiting. AIM: To compare COMT genotype of patients with PONV to PONV-free controls and to assess the possible relationship between genetic factors and dexamethasone response. A greater proportion of COMT-deficient allele is expected in PONV patients as compared to PONV-free controls. METHODS: The study population consists in all patients with PONV that are included in the main study (n=560). The control group will be 560 consenting patients but who do not develop PONV. COMT genotyping: Genomic DNA will be extracted from 200 µl of whole blood using the QIAamp DNA blood mini kit (QIAGEN, Hombrechtikon, Switzerland). The COMT Val158Met polymorphism (rs4680) will be genotyped using a commercially available TaqMan® SNP genotyping assay (C_25746809_50, Applied Biosystems, Warrington, UK). Twenty-five µl reactions will be performed using 50 ng of template DNA, pre-designed PCR primers and TaqMan® MGB probes (FAMTM and VIC® dye-labelled) according to the manufacturer's instructions in TaqMan® Universal PCR Master Mix using an iCycler iQ detection system (Bio-Rad, Hercules, CA). Analyses: The investigators will analyse allele and genotype frequencies, Hardyweinberg equilibrium, linkage disequilibrium and haplotypes. The individual SNPs and haplotypes association with of occurrence of PONV will be categorized and will be analyzed by Fisher exact test or Chi-square test and regression analysis (logistic, univariate and multivariate). Gene-gene interactions relation with that of PONV will be assessed by multivariate regression analysis. Analyses will be performed using Haploview software v1. (Broad Institute, Cambridge, USA) and SPSS (version 19; SPSS Inc, Chicag0, IL).