Elevated Risk of Fluoropyrimidine-Associated Toxicity in European Patients with DPYD Genetic Polymorphism: A Systematic Review and Meta-Analysis
Fluoropyrimidine is widely used owing to its clinical efficacy, however, patients with dihydropyrimidine dehydrogenase (DPD) deficiency can experience fluoropyrimidine-associated toxicity. The dihydropyrimidine dehydrogenase ( ) gene encodes DPD, and studies suggest that polymorphisms can result in...
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description | Fluoropyrimidine is widely used owing to its clinical efficacy, however, patients with dihydropyrimidine dehydrogenase (DPD) deficiency can experience fluoropyrimidine-associated toxicity. The dihydropyrimidine dehydrogenase (
) gene encodes DPD, and studies suggest that
polymorphisms can result in DPD deficiency. Since there is not a complete consistency of how much the risk of complication is elevated, we aimed to conduct a systematic literature review and a meta-analysis to provide the risk of fluoropyrimidine-associated toxicity in patients with
rs1801160 polymorphism.
We searched for qualifying studies published before October 2021 from PubMed, Web of Science, and EMBASE based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between rs1801160 polymorphism and toxicities. A sensitivity analysis using the leave-one-out method was performed on the overall toxicity.
The pooled OR for overall toxicity in the patients with A allele was elevated 1.73 times higher than those with the GG genotype (95% CI 1.44-2.07). Sensitivity analysis yielded similar results, showing the robustness of the result. Subjects with variants showed a 2.37-fold increased hematological toxicity (95% CI 1.48-3.81); especially a 1.87-fold increased neutropenia compared to patients with wildtype (95% CI 1.49-2.34). Patients with A allele revealed 1.22 times higher gastrointestinal toxicity compared to those with GG genotype (95% CI 0.93-1.61), and among gastrointestinal toxicity, the risk of diarrhea was elevated 1.43 times higher in those with variants than patients with wildtype (95% CI 1.12-1.83).
rs1801160 polymorphism is associated with elevated fluoropyrimidine-associated toxicity. Therefore, rs1801160 can be a potential candidate for DPD deficiency screening prior to fluoropyrimidine-based regimen. |
doi_str_mv | 10.3390/jpm12020225 |
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) gene encodes DPD, and studies suggest that
polymorphisms can result in DPD deficiency. Since there is not a complete consistency of how much the risk of complication is elevated, we aimed to conduct a systematic literature review and a meta-analysis to provide the risk of fluoropyrimidine-associated toxicity in patients with
rs1801160 polymorphism.
We searched for qualifying studies published before October 2021 from PubMed, Web of Science, and EMBASE based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between rs1801160 polymorphism and toxicities. A sensitivity analysis using the leave-one-out method was performed on the overall toxicity.
The pooled OR for overall toxicity in the patients with A allele was elevated 1.73 times higher than those with the GG genotype (95% CI 1.44-2.07). Sensitivity analysis yielded similar results, showing the robustness of the result. Subjects with variants showed a 2.37-fold increased hematological toxicity (95% CI 1.48-3.81); especially a 1.87-fold increased neutropenia compared to patients with wildtype (95% CI 1.49-2.34). Patients with A allele revealed 1.22 times higher gastrointestinal toxicity compared to those with GG genotype (95% CI 0.93-1.61), and among gastrointestinal toxicity, the risk of diarrhea was elevated 1.43 times higher in those with variants than patients with wildtype (95% CI 1.12-1.83).
rs1801160 polymorphism is associated with elevated fluoropyrimidine-associated toxicity. Therefore, rs1801160 can be a potential candidate for DPD deficiency screening prior to fluoropyrimidine-based regimen.</description><identifier>ISSN: 2075-4426</identifier><identifier>EISSN: 2075-4426</identifier><identifier>DOI: 10.3390/jpm12020225</identifier><identifier>PMID: 35207713</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Alleles ; Bias ; Cancer ; Dehydrogenases ; Diarrhea ; Gene polymorphism ; Genotype & phenotype ; Hematology ; Literature reviews ; Meta-analysis ; Metabolism ; Metabolites ; Neutropenia ; Patients ; Polymorphism ; Precision medicine ; Sensitivity analysis ; Toxicity</subject><ispartof>Journal of personalized medicine, 2022-02, Vol.12 (2), p.225</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-5a9e1503bc93f8bf47cc4f59cdb544532fe1355d3ad3bfff4f0c6cbc8662310d3</citedby><cites>FETCH-LOGICAL-c409t-5a9e1503bc93f8bf47cc4f59cdb544532fe1355d3ad3bfff4f0c6cbc8662310d3</cites><orcidid>0000-0002-9484-7792</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875904/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875904/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35207713$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Woorim</creatorcontrib><creatorcontrib>Cho, Young-Ah</creatorcontrib><creatorcontrib>Kim, Dong-Chul</creatorcontrib><creatorcontrib>Lee, Kyung-Eun</creatorcontrib><title>Elevated Risk of Fluoropyrimidine-Associated Toxicity in European Patients with DPYD Genetic Polymorphism: A Systematic Review and Meta-Analysis</title><title>Journal of personalized medicine</title><addtitle>J Pers Med</addtitle><description>Fluoropyrimidine is widely used owing to its clinical efficacy, however, patients with dihydropyrimidine dehydrogenase (DPD) deficiency can experience fluoropyrimidine-associated toxicity. The dihydropyrimidine dehydrogenase (
) gene encodes DPD, and studies suggest that
polymorphisms can result in DPD deficiency. Since there is not a complete consistency of how much the risk of complication is elevated, we aimed to conduct a systematic literature review and a meta-analysis to provide the risk of fluoropyrimidine-associated toxicity in patients with
rs1801160 polymorphism.
We searched for qualifying studies published before October 2021 from PubMed, Web of Science, and EMBASE based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between rs1801160 polymorphism and toxicities. A sensitivity analysis using the leave-one-out method was performed on the overall toxicity.
The pooled OR for overall toxicity in the patients with A allele was elevated 1.73 times higher than those with the GG genotype (95% CI 1.44-2.07). Sensitivity analysis yielded similar results, showing the robustness of the result. Subjects with variants showed a 2.37-fold increased hematological toxicity (95% CI 1.48-3.81); especially a 1.87-fold increased neutropenia compared to patients with wildtype (95% CI 1.49-2.34). Patients with A allele revealed 1.22 times higher gastrointestinal toxicity compared to those with GG genotype (95% CI 0.93-1.61), and among gastrointestinal toxicity, the risk of diarrhea was elevated 1.43 times higher in those with variants than patients with wildtype (95% CI 1.12-1.83).
rs1801160 polymorphism is associated with elevated fluoropyrimidine-associated toxicity. Therefore, rs1801160 can be a potential candidate for DPD deficiency screening prior to fluoropyrimidine-based regimen.</description><subject>Alleles</subject><subject>Bias</subject><subject>Cancer</subject><subject>Dehydrogenases</subject><subject>Diarrhea</subject><subject>Gene polymorphism</subject><subject>Genotype & phenotype</subject><subject>Hematology</subject><subject>Literature reviews</subject><subject>Meta-analysis</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Neutropenia</subject><subject>Patients</subject><subject>Polymorphism</subject><subject>Precision medicine</subject><subject>Sensitivity analysis</subject><subject>Toxicity</subject><issn>2075-4426</issn><issn>2075-4426</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNpdkUtv1DAUhS0EolXpij2yxAYJBRw_MgkLpFE7LUhFjEpZsLIc55rxkNjBdqbkX_CTcR9UA9eLa-l8OrpHB6HnJXnDWEPebsehpCQ_Kh6hQ0oWouCcVo_3_gfoOMYtyVMLSivyFB0wkdVFyQ7R71UPO5Wgw5c2_sDe4LN-8sGPc7CD7ayDYhmj1_aWufK_rLZpxtbh1ZQpUA6vVbLgUsTXNm3w6frbKT4HB8lqvPb9PPgwbmwc3uEl_jLHBIO6kS5hZ-EaK9fhT5BUsXSqn6ONz9ATo_oIx_f7CH09W12dfCguPp9_PFleFJqTJhVCNVAKwlrdMFO3hi-05kY0umsF54JRAyUTomOqY60xhhuiK93quqooK0nHjtD7O99xagfodE4QVC_HHFuFWXpl5b-Ksxv53e9kXS9EQ3g2eHVvEPzPCWKSg40a-l458FOUtMoFcVI2LKMv_0O3fgo58C1Fa8oFJ5l6fUfp4GMMYB6OKYm8KVvulZ3pF_v3P7B_q2V_AP9bp9k</recordid><startdate>20220206</startdate><enddate>20220206</enddate><creator>Kim, Woorim</creator><creator>Cho, Young-Ah</creator><creator>Kim, Dong-Chul</creator><creator>Lee, Kyung-Eun</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9484-7792</orcidid></search><sort><creationdate>20220206</creationdate><title>Elevated Risk of Fluoropyrimidine-Associated Toxicity in European Patients with DPYD Genetic Polymorphism: A Systematic Review and Meta-Analysis</title><author>Kim, Woorim ; Cho, Young-Ah ; Kim, Dong-Chul ; Lee, Kyung-Eun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-5a9e1503bc93f8bf47cc4f59cdb544532fe1355d3ad3bfff4f0c6cbc8662310d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Alleles</topic><topic>Bias</topic><topic>Cancer</topic><topic>Dehydrogenases</topic><topic>Diarrhea</topic><topic>Gene polymorphism</topic><topic>Genotype & phenotype</topic><topic>Hematology</topic><topic>Literature reviews</topic><topic>Meta-analysis</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Neutropenia</topic><topic>Patients</topic><topic>Polymorphism</topic><topic>Precision medicine</topic><topic>Sensitivity analysis</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Woorim</creatorcontrib><creatorcontrib>Cho, Young-Ah</creatorcontrib><creatorcontrib>Kim, Dong-Chul</creatorcontrib><creatorcontrib>Lee, Kyung-Eun</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of personalized medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Woorim</au><au>Cho, Young-Ah</au><au>Kim, Dong-Chul</au><au>Lee, Kyung-Eun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Elevated Risk of Fluoropyrimidine-Associated Toxicity in European Patients with DPYD Genetic Polymorphism: A Systematic Review and Meta-Analysis</atitle><jtitle>Journal of personalized medicine</jtitle><addtitle>J Pers Med</addtitle><date>2022-02-06</date><risdate>2022</risdate><volume>12</volume><issue>2</issue><spage>225</spage><pages>225-</pages><issn>2075-4426</issn><eissn>2075-4426</eissn><abstract>Fluoropyrimidine is widely used owing to its clinical efficacy, however, patients with dihydropyrimidine dehydrogenase (DPD) deficiency can experience fluoropyrimidine-associated toxicity. The dihydropyrimidine dehydrogenase (
) gene encodes DPD, and studies suggest that
polymorphisms can result in DPD deficiency. Since there is not a complete consistency of how much the risk of complication is elevated, we aimed to conduct a systematic literature review and a meta-analysis to provide the risk of fluoropyrimidine-associated toxicity in patients with
rs1801160 polymorphism.
We searched for qualifying studies published before October 2021 from PubMed, Web of Science, and EMBASE based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between rs1801160 polymorphism and toxicities. A sensitivity analysis using the leave-one-out method was performed on the overall toxicity.
The pooled OR for overall toxicity in the patients with A allele was elevated 1.73 times higher than those with the GG genotype (95% CI 1.44-2.07). Sensitivity analysis yielded similar results, showing the robustness of the result. Subjects with variants showed a 2.37-fold increased hematological toxicity (95% CI 1.48-3.81); especially a 1.87-fold increased neutropenia compared to patients with wildtype (95% CI 1.49-2.34). Patients with A allele revealed 1.22 times higher gastrointestinal toxicity compared to those with GG genotype (95% CI 0.93-1.61), and among gastrointestinal toxicity, the risk of diarrhea was elevated 1.43 times higher in those with variants than patients with wildtype (95% CI 1.12-1.83).
rs1801160 polymorphism is associated with elevated fluoropyrimidine-associated toxicity. Therefore, rs1801160 can be a potential candidate for DPD deficiency screening prior to fluoropyrimidine-based regimen.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>35207713</pmid><doi>10.3390/jpm12020225</doi><orcidid>https://orcid.org/0000-0002-9484-7792</orcidid><oa>free_for_read</oa></addata></record> |
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source | MDPI - Multidisciplinary Digital Publishing Institute; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
subjects | Alleles Bias Cancer Dehydrogenases Diarrhea Gene polymorphism Genotype & phenotype Hematology Literature reviews Meta-analysis Metabolism Metabolites Neutropenia Patients Polymorphism Precision medicine Sensitivity analysis Toxicity |
title | Elevated Risk of Fluoropyrimidine-Associated Toxicity in European Patients with DPYD Genetic Polymorphism: A Systematic Review and Meta-Analysis |
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