Can population differences in chemotherapy outcomes be inferred from differences in pharmacogenetic frequencies

Inter-ethnic differences in drug handling and frequencies of pharmacogenetic variants are increasingly being characterized. In this study, we systematically assessed the feasibility of inferring ethnic trends in chemotherapy outcomes from inter-ethnic differences in pharmacogenetic variant frequenci...

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Main Authors: Loh, M., Chua, D., Yao, Y., Soo, R., Garrett, K., Zeps, Nikolajs, Platell, C., Minamoto, T., Kawakami, K., Iacopetta, B., Soong, R.
Format: Journal Article
Published: 2013
Online Access:http://hdl.handle.net/20.500.11937/21055
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author Loh, M.
Chua, D.
Yao, Y.
Soo, R.
Garrett, K.
Zeps, Nikolajs
Platell, C.
Minamoto, T.
Kawakami, K.
Iacopetta, B.
Soong, R.
author_facet Loh, M.
Chua, D.
Yao, Y.
Soo, R.
Garrett, K.
Zeps, Nikolajs
Platell, C.
Minamoto, T.
Kawakami, K.
Iacopetta, B.
Soong, R.
author_sort Loh, M.
building Curtin Institutional Repository
collection Online Access
description Inter-ethnic differences in drug handling and frequencies of pharmacogenetic variants are increasingly being characterized. In this study, we systematically assessed the feasibility of inferring ethnic trends in chemotherapy outcomes from inter-ethnic differences in pharmacogenetic variant frequencies. Frequencies of 51 variants and chemotherapy outcomes of East Asian and Caucasian colorectal cancer patients on standard chemotherapy regimens were summarized by meta-analyses, and variant frequencies were validated by MassARRAY analysis. Inferences of relative chemotherapy outcomes were made by considering minor allele function and population differences in their frequency. Significant population differences in genotype distributions were observed for 13/23 (60%) and 27/35 (77%) variants in the meta-analyses and validation series, respectively. Across chemotherapy regimens, East Asians had lower rates of grade 3/4 toxicity for diarrhea and stomatitis/mucositis than Caucasians, which was correctly inferred from 13/18 (72%, P=0.018) informative genetic variants. With appropriate variant selection, inferring relative population toxicity rates from population genotype differences may be relevant.
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spelling curtin-20.500.11937-210552017-09-13T13:45:15Z Can population differences in chemotherapy outcomes be inferred from differences in pharmacogenetic frequencies Loh, M. Chua, D. Yao, Y. Soo, R. Garrett, K. Zeps, Nikolajs Platell, C. Minamoto, T. Kawakami, K. Iacopetta, B. Soong, R. Inter-ethnic differences in drug handling and frequencies of pharmacogenetic variants are increasingly being characterized. In this study, we systematically assessed the feasibility of inferring ethnic trends in chemotherapy outcomes from inter-ethnic differences in pharmacogenetic variant frequencies. Frequencies of 51 variants and chemotherapy outcomes of East Asian and Caucasian colorectal cancer patients on standard chemotherapy regimens were summarized by meta-analyses, and variant frequencies were validated by MassARRAY analysis. Inferences of relative chemotherapy outcomes were made by considering minor allele function and population differences in their frequency. Significant population differences in genotype distributions were observed for 13/23 (60%) and 27/35 (77%) variants in the meta-analyses and validation series, respectively. Across chemotherapy regimens, East Asians had lower rates of grade 3/4 toxicity for diarrhea and stomatitis/mucositis than Caucasians, which was correctly inferred from 13/18 (72%, P=0.018) informative genetic variants. With appropriate variant selection, inferring relative population toxicity rates from population genotype differences may be relevant. 2013 Journal Article http://hdl.handle.net/20.500.11937/21055 10.1038/tpj.2012.26 restricted
spellingShingle Loh, M.
Chua, D.
Yao, Y.
Soo, R.
Garrett, K.
Zeps, Nikolajs
Platell, C.
Minamoto, T.
Kawakami, K.
Iacopetta, B.
Soong, R.
Can population differences in chemotherapy outcomes be inferred from differences in pharmacogenetic frequencies
title Can population differences in chemotherapy outcomes be inferred from differences in pharmacogenetic frequencies
title_full Can population differences in chemotherapy outcomes be inferred from differences in pharmacogenetic frequencies
title_fullStr Can population differences in chemotherapy outcomes be inferred from differences in pharmacogenetic frequencies
title_full_unstemmed Can population differences in chemotherapy outcomes be inferred from differences in pharmacogenetic frequencies
title_short Can population differences in chemotherapy outcomes be inferred from differences in pharmacogenetic frequencies
title_sort can population differences in chemotherapy outcomes be inferred from differences in pharmacogenetic frequencies
url http://hdl.handle.net/20.500.11937/21055