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 effects (vomiting, nausea), nephrotoxicity, and hepatotoxicity, occurring in overall, early, or recurrent settings. The cumulative risk of overall symptoms of anemia was connected with <i>AKR1C3</i> rs3209896 AG, <i>ERCC1</i> rs3212986 GT, and >6 cycles of chemotherapy; leukopenia was determined by <i>ABCC1</i> rs129081 allele G and <i>DPYD</i> rs291593 allele T; neutropenia risk was correlated with accumulation of genetic variants of <i>DPYD</i> rs291583 allele G, <i>ABCB1</i> rs17064 AT, and positive HER2 status. Risk of nephrotoxicity was determined by homozygote <i>DPYD</i> rs291593, homozygote <i>AKR1C3</i> rs3209896, postmenopausal age, and negative ER status. Increased risk of hepatotoxicity was connected with <i>NR1/2</i> 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.