Effect of DPYD, MTHFR, ABCB1, XRCC1, ERCC1 and GSTP1 on chemotherapy related toxicity in colorectal carcinoma.

Autor: Puerta-García E; Pharmacy Service, Pharmacogenetics Unit. University, Hospital Virgen de las Nieves, Granada, Av. de las Fuerzas Armadas, 2, 18014 Granada, Spain. Electronic address: elenapuert@gmail.com., Urbano-Pérez D; Pharmacy Service, Pharmacogenetics Unit. University, Hospital Virgen de las Nieves, Granada, Av. de las Fuerzas Armadas, 2, 18014 Granada, Spain. Electronic address: davidurbanopv@gmail.com., Carrasco-Campos MI; Pharmacy Service, Pharmacogenetics Unit. University, Hospital Virgen de las Nieves, Granada, Av. de las Fuerzas Armadas, 2, 18014 Granada, Spain. Electronic address: mariaisabelcarrascocampos@gmail.com., Pérez-Ramírez C; Department of Social Pharmacy, Faculty of Pharmacy. University of Lisbon, Av. Prof. Gama. Pinto, 1600-083, Lisbon, Lisboa e Vale do Tejo, Portugal. Electronic address: mariaisabelcarrascocampos@gmail.com., Segura-Pérez A; Pathology Department, Universitary Hospital Campus de la, Salud, Granada, Av. de la Investigación, s/n, 18016, Granada, Spain. Electronic address: anichu29@hotmail.com., Calleja-Hernández; Department of Pharmacy, Unidad de Gestion Clinica (UGC), University Hospital Virgen Macarena, Sevilla, Calle Dr. Fedriani, 3, 41009, Sevilla, Spain. Electronic address: mangel.calleja.sspa@juntadeandalucia.es., Cañadas-Garre M; Epidemiology and Public Health Research Group Centre for Public Health, Queen's University of Belfast, Belfast, Northern Ireland, United Kingdom. Electronic address: m.canadasgarre@qub.ac.uk.
Jazyk: angličtina
Zdroj: Surgical oncology [Surg Oncol] 2020 Dec; Vol. 35, pp. 388-398. Date of Electronic Publication: 2020 Sep 19.
DOI: 10.1016/j.suronc.2020.09.016
Abstrakt: ABCB1, DPYD, MHTFR, XRCC1, ERCC1, GSTP1 and UGT1A1 genetic variants affect proteins related to CRC chemotherapy toxicity. A retrospective cohort study was conducted in 194 CRC patients. In first line treatment, DPYD rs17376848 AG genotype was associated with hematological toxicity (OR = 4.85; p = 0.03); GSTP1 G-allele (OR = 3.01; p = 0.005) and MTHFR rs1801133 T allele (OR = 2.51; p = 0.03) with respiratory toxicity; GSTP1 G-allele with cardiovascular toxicity (OR = 4.05; p = 0.01); ERCC1 rs11615 GG genotype with neurological toxicity (OR = 3.98; p = 0.01) and with asthenia (OR = 2.91; p = 0.08); XRCC1 rs1799782 T allele (OR = 0.31; p = 0.03) and GSTP1 G-allele (OR = 1.81; p = 0.01) with cutaneous toxicity. In second line treatment, XRCC1 rs1799782 T-allele was associated with asthenia (OR = 0.17; p = 0.03) and XRCC1 rs25487 T-allele with gastrointestinal toxicity (OR = 3.03; p = 0.005). After stratifying by treatment, in the 5-Fluorouracil group, the DPYD rs17376848 AG genotype was associated with hematological toxicity (OR = 2.76; p = 0.003), ABCB1 rs1045642 T-allele with the need of treatment adjustment due to toxicity (OR = 3.06; p = 0.01), and rs1045642 CC genotype with gastrointestinal toxicity (OR = 5.80; p = 0.03). In the capecitabine group, the MTHFR rs1801131 CC genotype was associated with asthenia (OR = 3.48; p = 0.009). In the oxaliplatin group, rs1045642 TT genotype was associated with the need to adjust treatment (OR = 0.32; p = 0.02), ERCC1 rs11615 GG genotype with asthenia (OR = 3.01; p = 0.01) and rs1615 GSTP1 GG genotype with respiratory toxicity (OR = 5.07; p = 0.009). ABCB1 rs1045642 T-allele reduces the need for treatment modification with both 5FU and oxaliplatin. Although several biomarkers predicted different toxic effects, they cannot be considered as risk factors for severe toxicity.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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