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. 2019 Jan 31;19(1):113.
doi: 10.1186/s12885-019-5310-4.

Opioid response in paediatric cancer patients and the Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene: an Italian study on 87 cancer children and a systematic review

Ersilia Lucenteforte  1 , Alfredo Vannacci  2 , Giada Crescioli  2 , Niccolò Lombardi  2 , Laura Vagnoli  3 , Laura Giunti  4 , Valentina Cetica  5 , Maria Luisa Coniglio  6 , Alessandra Pugi  7 , Roberto Bonaiuti  2 , Maurizio Aricò  8 , Sabrina Giglio  4   9 , Andrea Messeri  3 , Roberto Barale  10 , Lisa Giovannelli  2 , Alessandro Mugelli  2 , Valentina Maggini  11   12
Affiliations

Opioid response in paediatric cancer patients and the Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene: an Italian study on 87 cancer children and a systematic review

Ersilia Lucenteforte et al. BMC Cancer. .

Abstract

Background: Genetic polymorphisms in genes involved in pain modulation have been reported to be associated to opioid efficacy and safety in different clinical settings.

Methods: The association between COMT Val158Met polymorphism (rs4680) and the inter-individual differences in the response to opioid analgesic therapy was investigated in a cohort of 87 Italian paediatric patients receiving opioids for cancer pain (STOP Pain study). Furthermore, a systematic review of the association between opioid response in cancer patients and the COMT polymorphism was performed in accordance with the Cochrane Handbook and the Prisma Statement.

Results: In the 87 paediatric patients, pain intensity (total time needed to reach the lowest possible level) was significantly higher for G/G than A/G and A/A carriers (p-value = 0.042). In the 60 patients treated only with morphine, the mean of total dose to reach the same pain intensity was significantly higher for G/G than A/G and A/A carriers (p-value = 0.010). Systematic review identified five studies on adults, reporting that opioid dose (mg after 24 h of treatment from the first pain measurement) was higher for G/G compared to A/G and A/A carriers.

Conclusions: Present research suggests that the A allele in COMT polymorphism could be a marker of opioid sensitivity in paediatric cancer patients (STOP Pain), as well as in adults (Systematic Review), indicating that the polymorphism impact could be not age-dependent in the cancer pain context.

Trial registration: Registration number: CRD42017057831 .

Keywords: Cancer pain; Children; Genetic polymorphisms; Opioid; Systematic review.

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Conflict of interest statement

Ethics approval and consent to participate

The STOP Pain study obtained ethics approval from the institutional review board at Meyer Children’s Hospital (Protocol letter 9116/2010, December 14, 2010). Written informed consent to participate in the study was obtained from each patient (or their parent or legal guardian).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
PRISMA Flow diagram of the selection of studies searched with PUMBED and EMBASE and included in the systematic review
Fig. 2
Fig. 2
Forest plot of the comparison of STOP Pain data with those included in the systematic review, relative to the 24-h opioid cumulative dose (when reported as mean ± SD)
See this image and copyright information in PMC

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