Are the common genetic 3’UTR variants in ADME genes playing a role in tolerance of breast cancer chemotherapy?

Abstract

Abstract We described associations among 3’UTR genetic variants in ADME genes, clinical factors and the risk of toxicity or side effects of breast cancer chemotherapy. The SNPs in breast cancer women were tested in relation to 12 symptoms belonging to myelotoxicity (anemia, leukopenia, neutropenia), gastrointestinal side effects (vomiting, nausea), nephrotoxicity and hepatotoxicity, occurred 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; leucopenia was determined by ABCC1 rs129081 allele G and DPYD rs291593 allele T; neutropenia risk 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.