Influence of FPGS, ABCC4, SLC29A1, and MTHFR genes on the pharmacogenomics of fluoropyrimidines in patients with gastrointestinal cancer from the Brazilian Amazon
Purpose Fluoropyrimidines are one of the most used drug class to treat cancer patients, although they show high levels of associated toxicity. This study analyzed 33 polymorphisms in 17 pharmacogenes involved with the pharmacogenomics of fluoropyrimidines, in gastrointestinal cancer patients undergo...
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| Veröffentlicht in: | Cancer chemotherapy and pharmacology 2021-11, Vol.88 (5), p.837-844 |
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| creator | Fernandes, Marianne Rodrigues Rodrigues, Juliana Carla Gomes Dobbin, Elizabeth Ayres Fragoso Pastana, Lucas Favacho da Costa, Danielle Feio Barra, Williams Fernandes Modesto, Antônio André Conde de Assumpção, Paula Baraúna da Costa Silva, Artur Luiz dos Santos, Sidney Emanuel Batista Burbano, Rommel Mario Rodriguez de Assumpção, Paulo Pimentel dos Santos, Ney Pereira Carneiro |
| description | Purpose
Fluoropyrimidines are one of the most used drug class to treat cancer patients, although they show high levels of associated toxicity. This study analyzed 33 polymorphisms in 17 pharmacogenes involved with the pharmacogenomics of fluoropyrimidines, in gastrointestinal cancer patients undergoing fluoropyrimidine-based treatment in the Brazilian Amazon.
Methods
The study population was composed of 216 patients, 92 of whom have an anatomopathological diagnosis of gastric cancer and 124 of colorectal cancer. The single nucleotide polymorphisms (SNP) were genotyped by allelic discrimination using the TaqMan OpenArray Genotyping technology, with a panel of 32 customized assays, run in a QuantStudio ™ 12K Flex Real-Time PCR System (Applied Biosystems, Life Technologies, Carlsbad USA). Ancestry analysis was performed using 61 autosomal ancestry informative markers (AIMs).
Results
The study population show mean values of 48.1% European, 31.1% Amerindian, and 20.8% African ancestries. A significant risk association for general and severe toxicity was found in the rs4451422 of
FPGS
(
p
= 0.001; OR 3.40; CI 95% 1.65–7.00 and
p
= 0.006; OR 4.63; CI 95% 1.56–13.72, respectively) and the rs9524885 of
ABCC4
(
p
= 0.023; OR 2.74; CI 95% 1.14–6.65 and
p
= 0.024; OR 5.36; IC 95% 1.24–23.11, respectively) genes. The rs760370 in the
SLC29A1
gene (
p
= 0.009; OR 6.71; CI 95% 1.16–8.21) and the rs1801133 in the
MTHFR
toxicity (
p
= 0.023; OR 3.09; CI 95% 1.16–8.21) gene also demonstrated to be significant, although only for severe toxicity. The results found in this study did not have statistics analysis correction.
Conclusion
Four polymorphisms of the
ABCC4
,
FPGS
,
SLC29A1,
and
MTHFR
genes are likely to be potential predictive biomarkers for precision medicine in fluoropyrimidine-based treatments in the population of the Brazilian Amazon, which is constituted by a unique genetic background. |
| doi_str_mv | 10.1007/s00280-021-04327-w |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2557229739</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2577917040</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-62c4ed0e69dc79b7c14f91375849649743f62f9eaae200bf951e9c218eb83bf63</originalsourceid><addsrcrecordid>eNp9kc1u1DAURi0EotPCC7BAlth0MQH_JY6X04hpKw0C0bK2HMeecZXYwU40ah-HJ62nU0BiwcqW7_G59v0AeIfRR4wQ_5QQIjUqEMEFYpTwYv8CLHDeFahm9CVYIMpYUXLETsBpSncIIYYpfQ1OKKMUlxVegF_X3vaz8drAYOH62-XNEq4umoYt4c2mIWKFl1D5Dn65vVp_h1vjTYLBw2ln4LhTcVA65MMwOJ0OguwKMYz30Q2ucwfYeTiqyRk_Jbh30w5uVZpicH4yaXJe9VCr3D1CG8Pw5L2I6sH1Tnm4GtRD8G_AK6v6ZN4-r2fgx_rzbXNVbL5eXjerTaEpL6eiIpqZDplKdJqLlmvMrMC5VDNRMcEZtRWxwihlCEKtFSU2QhNcm7amra3oGTg_escYfs75dXJwSZu-V96EOUlSlpwQwanI6Id_0Lswx_yZA8W5wHnmKFPkSOkYUorGyjHPRcV7iZE8JCiPCcqcoHxKUO7zpffP6rkdTPfnyu_IMkCPQMolvzXxb-__aB8B9nSmhQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2577917040</pqid></control><display><type>article</type><title>Influence of FPGS, ABCC4, SLC29A1, and MTHFR genes on the pharmacogenomics of fluoropyrimidines in patients with gastrointestinal cancer from the Brazilian Amazon</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Fernandes, Marianne Rodrigues ; Rodrigues, Juliana Carla Gomes ; Dobbin, Elizabeth Ayres Fragoso ; Pastana, Lucas Favacho ; da Costa, Danielle Feio ; Barra, Williams Fernandes ; Modesto, Antônio André Conde ; de Assumpção, Paula Baraúna ; da Costa Silva, Artur Luiz ; dos Santos, Sidney Emanuel Batista ; Burbano, Rommel Mario Rodriguez ; de Assumpção, Paulo Pimentel ; dos Santos, Ney Pereira Carneiro</creator><creatorcontrib>Fernandes, Marianne Rodrigues ; Rodrigues, Juliana Carla Gomes ; Dobbin, Elizabeth Ayres Fragoso ; Pastana, Lucas Favacho ; da Costa, Danielle Feio ; Barra, Williams Fernandes ; Modesto, Antônio André Conde ; de Assumpção, Paula Baraúna ; da Costa Silva, Artur Luiz ; dos Santos, Sidney Emanuel Batista ; Burbano, Rommel Mario Rodriguez ; de Assumpção, Paulo Pimentel ; dos Santos, Ney Pereira Carneiro</creatorcontrib><description>Purpose
Fluoropyrimidines are one of the most used drug class to treat cancer patients, although they show high levels of associated toxicity. This study analyzed 33 polymorphisms in 17 pharmacogenes involved with the pharmacogenomics of fluoropyrimidines, in gastrointestinal cancer patients undergoing fluoropyrimidine-based treatment in the Brazilian Amazon.
Methods
The study population was composed of 216 patients, 92 of whom have an anatomopathological diagnosis of gastric cancer and 124 of colorectal cancer. The single nucleotide polymorphisms (SNP) were genotyped by allelic discrimination using the TaqMan OpenArray Genotyping technology, with a panel of 32 customized assays, run in a QuantStudio ™ 12K Flex Real-Time PCR System (Applied Biosystems, Life Technologies, Carlsbad USA). Ancestry analysis was performed using 61 autosomal ancestry informative markers (AIMs).
Results
The study population show mean values of 48.1% European, 31.1% Amerindian, and 20.8% African ancestries. A significant risk association for general and severe toxicity was found in the rs4451422 of
FPGS
(
p
= 0.001; OR 3.40; CI 95% 1.65–7.00 and
p
= 0.006; OR 4.63; CI 95% 1.56–13.72, respectively) and the rs9524885 of
ABCC4
(
p
= 0.023; OR 2.74; CI 95% 1.14–6.65 and
p
= 0.024; OR 5.36; IC 95% 1.24–23.11, respectively) genes. The rs760370 in the
SLC29A1
gene (
p
= 0.009; OR 6.71; CI 95% 1.16–8.21) and the rs1801133 in the
MTHFR
toxicity (
p
= 0.023; OR 3.09; CI 95% 1.16–8.21) gene also demonstrated to be significant, although only for severe toxicity. The results found in this study did not have statistics analysis correction.
Conclusion
Four polymorphisms of the
ABCC4
,
FPGS
,
SLC29A1,
and
MTHFR
genes are likely to be potential predictive biomarkers for precision medicine in fluoropyrimidine-based treatments in the population of the Brazilian Amazon, which is constituted by a unique genetic background.</description><identifier>ISSN: 0344-5704</identifier><identifier>EISSN: 1432-0843</identifier><identifier>DOI: 10.1007/s00280-021-04327-w</identifier><identifier>PMID: 34331561</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Biomarkers ; Brazil ; Camptothecin - analogs & derivatives ; Camptothecin - pharmacology ; Cancer ; Cancer Research ; Colorectal cancer ; Colorectal carcinoma ; Equilibrative Nucleoside Transporter 1 - genetics ; Female ; Fluorouracil - administration & dosage ; Fluorouracil - pharmacokinetics ; Fluorouracil - pharmacology ; Gastric cancer ; Gastrointestinal cancer ; Gastrointestinal Neoplasms - drug therapy ; Gastrointestinal Neoplasms - genetics ; Genes ; Genotyping ; Humans ; Leucovorin - pharmacology ; Male ; Medicine ; Medicine & Public Health ; Methylenetetrahydrofolate reductase ; Methylenetetrahydrofolate Reductase (NADPH2) - genetics ; Middle Aged ; Multidrug Resistance-Associated Proteins - genetics ; Nucleotides ; Oncology ; Organoplatinum Compounds - pharmacology ; Original Article ; Patients ; Peptide Synthases - genetics ; Pharmacogenomic Variants ; Pharmacogenomics ; Pharmacology ; Pharmacology/Toxicology ; Polymorphism, Single Nucleotide ; Population studies ; Precision medicine ; Single-nucleotide polymorphism ; Statistical analysis ; Toxicity</subject><ispartof>Cancer chemotherapy and pharmacology, 2021-11, Vol.88 (5), p.837-844</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-62c4ed0e69dc79b7c14f91375849649743f62f9eaae200bf951e9c218eb83bf63</citedby><cites>FETCH-LOGICAL-c375t-62c4ed0e69dc79b7c14f91375849649743f62f9eaae200bf951e9c218eb83bf63</cites><orcidid>0000-0003-3289-390X ; 0000-0002-8803-4664 ; 0000-0002-1396-3442 ; 0000-0002-4872-234X ; 0000-0002-8622-9417 ; 0000-0001-8087-7037 ; 0000-0001-8954-4212 ; 0000-0003-1854-0358 ; 0000-0003-3846-8445 ; 0000-0002-7735-7732 ; 0000-0002-4082-1132 ; 0000-0003-2625-8037 ; 0000-0003-1665-3535</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00280-021-04327-w$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00280-021-04327-w$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34331561$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fernandes, Marianne Rodrigues</creatorcontrib><creatorcontrib>Rodrigues, Juliana Carla Gomes</creatorcontrib><creatorcontrib>Dobbin, Elizabeth Ayres Fragoso</creatorcontrib><creatorcontrib>Pastana, Lucas Favacho</creatorcontrib><creatorcontrib>da Costa, Danielle Feio</creatorcontrib><creatorcontrib>Barra, Williams Fernandes</creatorcontrib><creatorcontrib>Modesto, Antônio André Conde</creatorcontrib><creatorcontrib>de Assumpção, Paula Baraúna</creatorcontrib><creatorcontrib>da Costa Silva, Artur Luiz</creatorcontrib><creatorcontrib>dos Santos, Sidney Emanuel Batista</creatorcontrib><creatorcontrib>Burbano, Rommel Mario Rodriguez</creatorcontrib><creatorcontrib>de Assumpção, Paulo Pimentel</creatorcontrib><creatorcontrib>dos Santos, Ney Pereira Carneiro</creatorcontrib><title>Influence of FPGS, ABCC4, SLC29A1, and MTHFR genes on the pharmacogenomics of fluoropyrimidines in patients with gastrointestinal cancer from the Brazilian Amazon</title><title>Cancer chemotherapy and pharmacology</title><addtitle>Cancer Chemother Pharmacol</addtitle><addtitle>Cancer Chemother Pharmacol</addtitle><description>Purpose
Fluoropyrimidines are one of the most used drug class to treat cancer patients, although they show high levels of associated toxicity. This study analyzed 33 polymorphisms in 17 pharmacogenes involved with the pharmacogenomics of fluoropyrimidines, in gastrointestinal cancer patients undergoing fluoropyrimidine-based treatment in the Brazilian Amazon.
Methods
The study population was composed of 216 patients, 92 of whom have an anatomopathological diagnosis of gastric cancer and 124 of colorectal cancer. The single nucleotide polymorphisms (SNP) were genotyped by allelic discrimination using the TaqMan OpenArray Genotyping technology, with a panel of 32 customized assays, run in a QuantStudio ™ 12K Flex Real-Time PCR System (Applied Biosystems, Life Technologies, Carlsbad USA). Ancestry analysis was performed using 61 autosomal ancestry informative markers (AIMs).
Results
The study population show mean values of 48.1% European, 31.1% Amerindian, and 20.8% African ancestries. A significant risk association for general and severe toxicity was found in the rs4451422 of
FPGS
(
p
= 0.001; OR 3.40; CI 95% 1.65–7.00 and
p
= 0.006; OR 4.63; CI 95% 1.56–13.72, respectively) and the rs9524885 of
ABCC4
(
p
= 0.023; OR 2.74; CI 95% 1.14–6.65 and
p
= 0.024; OR 5.36; IC 95% 1.24–23.11, respectively) genes. The rs760370 in the
SLC29A1
gene (
p
= 0.009; OR 6.71; CI 95% 1.16–8.21) and the rs1801133 in the
MTHFR
toxicity (
p
= 0.023; OR 3.09; CI 95% 1.16–8.21) gene also demonstrated to be significant, although only for severe toxicity. The results found in this study did not have statistics analysis correction.
Conclusion
Four polymorphisms of the
ABCC4
,
FPGS
,
SLC29A1,
and
MTHFR
genes are likely to be potential predictive biomarkers for precision medicine in fluoropyrimidine-based treatments in the population of the Brazilian Amazon, which is constituted by a unique genetic background.</description><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>Antineoplastic Combined Chemotherapy Protocols - pharmacology</subject><subject>Biomarkers</subject><subject>Brazil</subject><subject>Camptothecin - analogs & derivatives</subject><subject>Camptothecin - pharmacology</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Equilibrative Nucleoside Transporter 1 - genetics</subject><subject>Female</subject><subject>Fluorouracil - administration & dosage</subject><subject>Fluorouracil - pharmacokinetics</subject><subject>Fluorouracil - pharmacology</subject><subject>Gastric cancer</subject><subject>Gastrointestinal cancer</subject><subject>Gastrointestinal Neoplasms - drug therapy</subject><subject>Gastrointestinal Neoplasms - genetics</subject><subject>Genes</subject><subject>Genotyping</subject><subject>Humans</subject><subject>Leucovorin - pharmacology</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Methylenetetrahydrofolate reductase</subject><subject>Methylenetetrahydrofolate Reductase (NADPH2) - genetics</subject><subject>Middle Aged</subject><subject>Multidrug Resistance-Associated Proteins - genetics</subject><subject>Nucleotides</subject><subject>Oncology</subject><subject>Organoplatinum Compounds - pharmacology</subject><subject>Original Article</subject><subject>Patients</subject><subject>Peptide Synthases - genetics</subject><subject>Pharmacogenomic Variants</subject><subject>Pharmacogenomics</subject><subject>Pharmacology</subject><subject>Pharmacology/Toxicology</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population studies</subject><subject>Precision medicine</subject><subject>Single-nucleotide polymorphism</subject><subject>Statistical analysis</subject><subject>Toxicity</subject><issn>0344-5704</issn><issn>1432-0843</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kc1u1DAURi0EotPCC7BAlth0MQH_JY6X04hpKw0C0bK2HMeecZXYwU40ah-HJ62nU0BiwcqW7_G59v0AeIfRR4wQ_5QQIjUqEMEFYpTwYv8CLHDeFahm9CVYIMpYUXLETsBpSncIIYYpfQ1OKKMUlxVegF_X3vaz8drAYOH62-XNEq4umoYt4c2mIWKFl1D5Dn65vVp_h1vjTYLBw2ln4LhTcVA65MMwOJ0OguwKMYz30Q2ucwfYeTiqyRk_Jbh30w5uVZpicH4yaXJe9VCr3D1CG8Pw5L2I6sH1Tnm4GtRD8G_AK6v6ZN4-r2fgx_rzbXNVbL5eXjerTaEpL6eiIpqZDplKdJqLlmvMrMC5VDNRMcEZtRWxwihlCEKtFSU2QhNcm7amra3oGTg_escYfs75dXJwSZu-V96EOUlSlpwQwanI6Id_0Lswx_yZA8W5wHnmKFPkSOkYUorGyjHPRcV7iZE8JCiPCcqcoHxKUO7zpffP6rkdTPfnyu_IMkCPQMolvzXxb-__aB8B9nSmhQ</recordid><startdate>20211101</startdate><enddate>20211101</enddate><creator>Fernandes, Marianne 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of FPGS, ABCC4, SLC29A1, and MTHFR genes on the pharmacogenomics of fluoropyrimidines in patients with gastrointestinal cancer from the Brazilian Amazon</title><author>Fernandes, Marianne Rodrigues ; Rodrigues, Juliana Carla Gomes ; Dobbin, Elizabeth Ayres Fragoso ; Pastana, Lucas Favacho ; da Costa, Danielle Feio ; Barra, Williams Fernandes ; Modesto, Antônio André Conde ; de Assumpção, Paula Baraúna ; da Costa Silva, Artur Luiz ; dos Santos, Sidney Emanuel Batista ; Burbano, Rommel Mario Rodriguez ; de Assumpção, Paulo Pimentel ; dos Santos, Ney Pereira Carneiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-62c4ed0e69dc79b7c14f91375849649743f62f9eaae200bf951e9c218eb83bf63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antineoplastic Combined Chemotherapy Protocols - adverse effects</topic><topic>Antineoplastic Combined Chemotherapy Protocols - pharmacology</topic><topic>Biomarkers</topic><topic>Brazil</topic><topic>Camptothecin - analogs & derivatives</topic><topic>Camptothecin - pharmacology</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Equilibrative Nucleoside Transporter 1 - genetics</topic><topic>Female</topic><topic>Fluorouracil - administration & dosage</topic><topic>Fluorouracil - pharmacokinetics</topic><topic>Fluorouracil - pharmacology</topic><topic>Gastric cancer</topic><topic>Gastrointestinal cancer</topic><topic>Gastrointestinal Neoplasms - drug therapy</topic><topic>Gastrointestinal Neoplasms - genetics</topic><topic>Genes</topic><topic>Genotyping</topic><topic>Humans</topic><topic>Leucovorin - pharmacology</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Methylenetetrahydrofolate reductase</topic><topic>Methylenetetrahydrofolate Reductase (NADPH2) - genetics</topic><topic>Middle Aged</topic><topic>Multidrug Resistance-Associated Proteins - genetics</topic><topic>Nucleotides</topic><topic>Oncology</topic><topic>Organoplatinum Compounds - pharmacology</topic><topic>Original Article</topic><topic>Patients</topic><topic>Peptide Synthases - genetics</topic><topic>Pharmacogenomic Variants</topic><topic>Pharmacogenomics</topic><topic>Pharmacology</topic><topic>Pharmacology/Toxicology</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population studies</topic><topic>Precision medicine</topic><topic>Single-nucleotide polymorphism</topic><topic>Statistical analysis</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fernandes, Marianne Rodrigues</creatorcontrib><creatorcontrib>Rodrigues, Juliana Carla Gomes</creatorcontrib><creatorcontrib>Dobbin, Elizabeth Ayres Fragoso</creatorcontrib><creatorcontrib>Pastana, Lucas Favacho</creatorcontrib><creatorcontrib>da Costa, Danielle Feio</creatorcontrib><creatorcontrib>Barra, Williams Fernandes</creatorcontrib><creatorcontrib>Modesto, Antônio André Conde</creatorcontrib><creatorcontrib>de Assumpção, Paula Baraúna</creatorcontrib><creatorcontrib>da Costa Silva, Artur Luiz</creatorcontrib><creatorcontrib>dos Santos, Sidney Emanuel Batista</creatorcontrib><creatorcontrib>Burbano, Rommel Mario Rodriguez</creatorcontrib><creatorcontrib>de Assumpção, Paulo Pimentel</creatorcontrib><creatorcontrib>dos Santos, Ney Pereira Carneiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 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USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer chemotherapy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fernandes, Marianne Rodrigues</au><au>Rodrigues, Juliana Carla Gomes</au><au>Dobbin, Elizabeth Ayres Fragoso</au><au>Pastana, Lucas Favacho</au><au>da Costa, Danielle Feio</au><au>Barra, Williams Fernandes</au><au>Modesto, Antônio André Conde</au><au>de Assumpção, Paula Baraúna</au><au>da Costa Silva, Artur Luiz</au><au>dos Santos, Sidney Emanuel Batista</au><au>Burbano, Rommel Mario Rodriguez</au><au>de Assumpção, Paulo Pimentel</au><au>dos Santos, Ney Pereira Carneiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of FPGS, ABCC4, SLC29A1, and MTHFR genes on the pharmacogenomics of fluoropyrimidines in patients with gastrointestinal cancer from the Brazilian Amazon</atitle><jtitle>Cancer chemotherapy and pharmacology</jtitle><stitle>Cancer Chemother Pharmacol</stitle><addtitle>Cancer Chemother Pharmacol</addtitle><date>2021-11-01</date><risdate>2021</risdate><volume>88</volume><issue>5</issue><spage>837</spage><epage>844</epage><pages>837-844</pages><issn>0344-5704</issn><eissn>1432-0843</eissn><abstract>Purpose
Fluoropyrimidines are one of the most used drug class to treat cancer patients, although they show high levels of associated toxicity. This study analyzed 33 polymorphisms in 17 pharmacogenes involved with the pharmacogenomics of fluoropyrimidines, in gastrointestinal cancer patients undergoing fluoropyrimidine-based treatment in the Brazilian Amazon.
Methods
The study population was composed of 216 patients, 92 of whom have an anatomopathological diagnosis of gastric cancer and 124 of colorectal cancer. The single nucleotide polymorphisms (SNP) were genotyped by allelic discrimination using the TaqMan OpenArray Genotyping technology, with a panel of 32 customized assays, run in a QuantStudio ™ 12K Flex Real-Time PCR System (Applied Biosystems, Life Technologies, Carlsbad USA). Ancestry analysis was performed using 61 autosomal ancestry informative markers (AIMs).
Results
The study population show mean values of 48.1% European, 31.1% Amerindian, and 20.8% African ancestries. A significant risk association for general and severe toxicity was found in the rs4451422 of
FPGS
(
p
= 0.001; OR 3.40; CI 95% 1.65–7.00 and
p
= 0.006; OR 4.63; CI 95% 1.56–13.72, respectively) and the rs9524885 of
ABCC4
(
p
= 0.023; OR 2.74; CI 95% 1.14–6.65 and
p
= 0.024; OR 5.36; IC 95% 1.24–23.11, respectively) genes. The rs760370 in the
SLC29A1
gene (
p
= 0.009; OR 6.71; CI 95% 1.16–8.21) and the rs1801133 in the
MTHFR
toxicity (
p
= 0.023; OR 3.09; CI 95% 1.16–8.21) gene also demonstrated to be significant, although only for severe toxicity. The results found in this study did not have statistics analysis correction.
Conclusion
Four polymorphisms of the
ABCC4
,
FPGS
,
SLC29A1,
and
MTHFR
genes are likely to be potential predictive biomarkers for precision medicine in fluoropyrimidine-based treatments in the population of the Brazilian Amazon, which is constituted by a unique genetic background.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>34331561</pmid><doi>10.1007/s00280-021-04327-w</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-3289-390X</orcidid><orcidid>https://orcid.org/0000-0002-8803-4664</orcidid><orcidid>https://orcid.org/0000-0002-1396-3442</orcidid><orcidid>https://orcid.org/0000-0002-4872-234X</orcidid><orcidid>https://orcid.org/0000-0002-8622-9417</orcidid><orcidid>https://orcid.org/0000-0001-8087-7037</orcidid><orcidid>https://orcid.org/0000-0001-8954-4212</orcidid><orcidid>https://orcid.org/0000-0003-1854-0358</orcidid><orcidid>https://orcid.org/0000-0003-3846-8445</orcidid><orcidid>https://orcid.org/0000-0002-7735-7732</orcidid><orcidid>https://orcid.org/0000-0002-4082-1132</orcidid><orcidid>https://orcid.org/0000-0003-2625-8037</orcidid><orcidid>https://orcid.org/0000-0003-1665-3535</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0344-5704 |
| ispartof | Cancer chemotherapy and pharmacology, 2021-11, Vol.88 (5), p.837-844 |
| issn | 0344-5704 1432-0843 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2557229739 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - pharmacology Biomarkers Brazil Camptothecin - analogs & derivatives Camptothecin - pharmacology Cancer Cancer Research Colorectal cancer Colorectal carcinoma Equilibrative Nucleoside Transporter 1 - genetics Female Fluorouracil - administration & dosage Fluorouracil - pharmacokinetics Fluorouracil - pharmacology Gastric cancer Gastrointestinal cancer Gastrointestinal Neoplasms - drug therapy Gastrointestinal Neoplasms - genetics Genes Genotyping Humans Leucovorin - pharmacology Male Medicine Medicine & Public Health Methylenetetrahydrofolate reductase Methylenetetrahydrofolate Reductase (NADPH2) - genetics Middle Aged Multidrug Resistance-Associated Proteins - genetics Nucleotides Oncology Organoplatinum Compounds - pharmacology Original Article Patients Peptide Synthases - genetics Pharmacogenomic Variants Pharmacogenomics Pharmacology Pharmacology/Toxicology Polymorphism, Single Nucleotide Population studies Precision medicine Single-nucleotide polymorphism Statistical analysis Toxicity |
| title | Influence of FPGS, ABCC4, SLC29A1, and MTHFR genes on the pharmacogenomics of fluoropyrimidines in patients with gastrointestinal cancer from the Brazilian Amazon |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T03%3A22%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Influence%20of%20FPGS,%20ABCC4,%20SLC29A1,%20and%20MTHFR%20genes%20on%20the%20pharmacogenomics%20of%20fluoropyrimidines%20in%20patients%20with%20gastrointestinal%20cancer%20from%20the%20Brazilian%20Amazon&rft.jtitle=Cancer%20chemotherapy%20and%20pharmacology&rft.au=Fernandes,%20Marianne%20Rodrigues&rft.date=2021-11-01&rft.volume=88&rft.issue=5&rft.spage=837&rft.epage=844&rft.pages=837-844&rft.issn=0344-5704&rft.eissn=1432-0843&rft_id=info:doi/10.1007/s00280-021-04327-w&rft_dat=%3Cproquest_cross%3E2577917040%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2577917040&rft_id=info:pmid/34331561&rfr_iscdi=true |