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De Mattia et al. Cancer Drug Resist 2019;2:116-30 I http://dx.doi.org/10.20517/cdr.2019.04 Page 127

demonstrated that a specific combination of MTHFR rs1801131 and TYMS 3’-UTR ins/del (rs16430)
[83]
polymorphisms, instead the single locus, could represent a significant predictor of increased toxicity risk .

A lot of research has been focused to define additional predictive biomarkers to increase the sensitivity of
the available pharmacogenetic tests for FP. A significant contribution in this sense could be provided by
the research on the rare genetic variants, what emerging role has been pointed out by the advancement
of the NGS technologies. From a recent revision of the 1K genome project results it appeared that about
30 to 40% of the inter-individual variability in drugs ADME (adsorption, distribution, metabolism, and
excretion) and nuclear receptors genes is related to rare genetic variants that are not commonly screened in
[84]
the pharmacogenetic studies and can be responsible for the observed variability in term of drug toxicity
and pharmacokinetics. It is likely that future research, based on new and more comprehensive genetic
analysis strategies will highlight more complex and heterogeneous genetic profiles addressing the issue of
unexplained severe toxic events occurrence.

DECLARATIONS
Authors’ contributions
Wrote the manuscript: De Mattia E
Performed the literature search: Roncato R, Dalle Fratte C
Elaborated the Figures: Ecca F
Guarantor: Toffoli G
Wrote and revised the manuscript: Cecchin E
Reviewed the manuscript: All authors

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.

REFERENCES
1. Pirmohamed M, James S, Meakin S, Green C, Scott AK, et al. Adverse drug reactions as cause of admission to hospital: prospective
analysis of 18 820 patients. BMJ 2004;329:15-9.
2. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies.
JAMA 1998;279:1200-5.
3. Rottenkolber D, Schmiedl S, Rottenkolber M, Farker K, Saljé K, et al. Adverse drug reactions in Germany: direct costs of internal
medicine hospitalizations. Pharmacoepidemiol Drug Saf 2011;20:626-34.
4. Gyllensten H, Hakkarainen KM, Hägg S, Carlsten A, Petzold M, et al. Economic impact of adverse drug events--a retrospective