Are the Common Genetic 3′UTR Variants in ADME Genes Playing a Role in Tolerance of Breast Cancer Chemotherapy?

We studied the associations between 3′UTR genetic variants in ADME genes, clinical factors, and the risk of breast cancer chemotherapy toxicity. Those variants and factors were tested in relation to seven symptoms belonging to myelotoxicity (anemia, leukopenia, neutropenia), gastrointestinal side ef...

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Bibliographic Details
Published in:International journal of molecular sciences 2024-11, Vol.25 (22), p.12283
Main Authors: Tęcza, Karolina, Kalinowska-Herok, Magdalena, Rusinek, Dagmara, Zajkowicz, Artur, Pfeifer, Aleksandra, Oczko-Wojciechowska, Małgorzata, Pamuła-Piłat, Jolanta
Format: Article
Language:English
Subjects:
Anemia
Antimitotic agents
Antineoplastic agents
Breast cancer
Cancer
Cancer therapies
Care and treatment
Chemotherapy
Drugs
Enzymes
Genes
Genetic aspects
Genetic research
Health aspects
Kidneys
Leukopenia
Medical prognosis
Metabolism
Metabolites
Methods
Postmenopausal women
Risk factors
Side effects
Toxicity
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Summary:We studied the associations between 3′UTR genetic variants in ADME genes, clinical factors, and the risk of breast cancer chemotherapy toxicity. Those variants and factors were tested in relation to seven symptoms belonging to myelotoxicity (anemia, leukopenia, neutropenia), gastrointestinal side effects (vomiting, nausea), nephrotoxicity, and hepatotoxicity, occurring in overall, early, or recurrent settings. The cumulative risk of overall symptoms of anemia was connected with AKR1C3 rs3209896 AG, ERCC1 rs3212986 GT, and >6 cycles of chemotherapy; leukopenia was determined by ABCC1 rs129081 allele G and DPYD rs291593 allele T; neutropenia risk was correlated with accumulation of genetic variants of DPYD rs291583 allele G, ABCB1 rs17064 AT, and positive HER2 status. Risk of nephrotoxicity was determined by homozygote DPYD rs291593, homozygote AKR1C3 rs3209896, postmenopausal age, and negative ER status. Increased risk of hepatotoxicity was connected with NR1/2 rs3732359 allele G, postmenopausal age, and with present metastases. The risk of nausea and vomiting was linked to several genetic factors and premenopausal age. We concluded that chemotherapy tolerance emerges from the simultaneous interaction of many genetic and clinical factors.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms252212283