The Correlation Between UGT1A1 Gene Phenotypes and the Clinical Prognosis of Advanced Colorectal Cancer After FOLFIRI Therapy
This study investigated the correlations between the different phenotypes of the uridine diphosphate glucuronyl transferase (UGT) 1A1 gene and the treatment of advanced colorectal cancer after the FOLFIRI regimen. A total of 240 advanced colorectal cancer patients with stage IV colon cancer or recur...
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| Veröffentlicht in: | Cancer biotherapy & radiopharmaceuticals 2021-11, Vol.36 (9), p.720-727 |
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| creator | Li, Xiao-Kai Wang, Wen-Ling Xu, Yu-Xuan Yang, Yuan Wang, Gang Dong, Hong-Min Chen, Wei-Wei Li, Guo-Dong |
| description | This study investigated the correlations between the different phenotypes of the uridine diphosphate glucuronyl transferase (UGT) 1A1 gene and the treatment of advanced colorectal cancer after the FOLFIRI regimen.
A total of 240 advanced colorectal cancer patients with stage IV colon cancer or recurrence after radical surgery between January 2014 and December 2018 were included in a retrospective study. All participants were treated with the FOLFIRI regimen until the disease progressed or an intolerable level of toxicity occurred.
In this study, three phenotypes of the UGT1A1 gene promoter were found: the homozygous wild type (TA6/6 type, 78.3%), the heterozygous mutant type (TA6/7 type, 19.6%), and the homozygous mutant type (TA7/7 type, 2.1%). Compared with TA6/7 and TA6/6, the risk of nonresponse to FOLFIRI chemotherapy increased by 16%, but the difference was not significant. The risk of death increased by 24%, and there was no significant difference. There was a risk of hematologic and nonhematologic adverse reactions occurring in TA6/7 and TA6/6, and the total risk of adverse reactions increased by 9.3773 times among patients with more than two metastatic organs. Compared with patients with TA6/6, the risk of toxic side-effects increased by 42.8066 times (
= 0.0259) for patients with TA6/7. Among patients who received FOLFIRI chemotherapy for more than four cycles, the proportion with TA6/7 was greater than that with TA6/6. Compared with those with TA6/6, patients with TA6/7 showed a higher risk of hematologic toxicity (22.3246 times,
= 0.0035).
The TA6/7 in patients with advanced colorectal cancer had more than two metastatic organs, and received FOLFIRI chemotherapy for more than four cycles compared with TA6/6 patients. Furthermore, the risk of hematologic and nonhematologic adverse reactions significantly increased, and the risk of digestive-tract and hematologic toxicity was more significant. |
| doi_str_mv | 10.1089/cbr.2020.4163 |
| format | Article |
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A total of 240 advanced colorectal cancer patients with stage IV colon cancer or recurrence after radical surgery between January 2014 and December 2018 were included in a retrospective study. All participants were treated with the FOLFIRI regimen until the disease progressed or an intolerable level of toxicity occurred.
In this study, three phenotypes of the UGT1A1 gene promoter were found: the homozygous wild type (TA6/6 type, 78.3%), the heterozygous mutant type (TA6/7 type, 19.6%), and the homozygous mutant type (TA7/7 type, 2.1%). Compared with TA6/7 and TA6/6, the risk of nonresponse to FOLFIRI chemotherapy increased by 16%, but the difference was not significant. The risk of death increased by 24%, and there was no significant difference. There was a risk of hematologic and nonhematologic adverse reactions occurring in TA6/7 and TA6/6, and the total risk of adverse reactions increased by 9.3773 times among patients with more than two metastatic organs. Compared with patients with TA6/6, the risk of toxic side-effects increased by 42.8066 times (
= 0.0259) for patients with TA6/7. Among patients who received FOLFIRI chemotherapy for more than four cycles, the proportion with TA6/7 was greater than that with TA6/6. Compared with those with TA6/6, patients with TA6/7 showed a higher risk of hematologic toxicity (22.3246 times,
= 0.0035).
The TA6/7 in patients with advanced colorectal cancer had more than two metastatic organs, and received FOLFIRI chemotherapy for more than four cycles compared with TA6/6 patients. Furthermore, the risk of hematologic and nonhematologic adverse reactions significantly increased, and the risk of digestive-tract and hematologic toxicity was more significant.</description><identifier>ISSN: 1084-9785</identifier><identifier>EISSN: 1557-8852</identifier><identifier>DOI: 10.1089/cbr.2020.4163</identifier><identifier>PMID: 33877904</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Biological Variation, Population ; Camptothecin - administration & dosage ; Camptothecin - adverse effects ; Camptothecin - analogs & derivatives ; Cancer therapies ; Chemotherapy ; China - epidemiology ; Colon cancer ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - pathology ; Colorectal Neoplasms - radiotherapy ; Correlation of Data ; Digestive System Diseases - chemically induced ; Digestive System Diseases - diagnosis ; Drug Resistance, Neoplasm - genetics ; Drug-Related Side Effects and Adverse Reactions - genetics ; Female ; Fluorouracil - administration & dosage ; Fluorouracil - adverse effects ; Glucuronosyltransferase - genetics ; Hematologic Diseases - chemically induced ; Hematologic Diseases - diagnosis ; Humans ; Leucovorin - administration & dosage ; Leucovorin - adverse effects ; Male ; Metastases ; Metastasis ; Middle Aged ; Mutants ; Neoplasm Staging ; Outcome and Process Assessment, Health Care ; Patients ; Phenotypes ; Prognosis ; Radiotherapy - methods ; Retrospective Studies ; Risk Assessment ; Side effects ; Toxicity ; Uridine</subject><ispartof>Cancer biotherapy & radiopharmaceuticals, 2021-11, Vol.36 (9), p.720-727</ispartof><rights>Copyright Mary Ann Liebert, Inc. Nov 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c321t-dc61f6e4bc2bb03720ce87a71f65decfceac6110688c778996f535b9a9355bbd3</citedby><cites>FETCH-LOGICAL-c321t-dc61f6e4bc2bb03720ce87a71f65decfceac6110688c778996f535b9a9355bbd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33877904$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Xiao-Kai</creatorcontrib><creatorcontrib>Wang, Wen-Ling</creatorcontrib><creatorcontrib>Xu, Yu-Xuan</creatorcontrib><creatorcontrib>Yang, Yuan</creatorcontrib><creatorcontrib>Wang, Gang</creatorcontrib><creatorcontrib>Dong, Hong-Min</creatorcontrib><creatorcontrib>Chen, Wei-Wei</creatorcontrib><creatorcontrib>Li, Guo-Dong</creatorcontrib><title>The Correlation Between UGT1A1 Gene Phenotypes and the Clinical Prognosis of Advanced Colorectal Cancer After FOLFIRI Therapy</title><title>Cancer biotherapy & radiopharmaceuticals</title><addtitle>Cancer Biother Radiopharm</addtitle><description>This study investigated the correlations between the different phenotypes of the uridine diphosphate glucuronyl transferase (UGT) 1A1 gene and the treatment of advanced colorectal cancer after the FOLFIRI regimen.
A total of 240 advanced colorectal cancer patients with stage IV colon cancer or recurrence after radical surgery between January 2014 and December 2018 were included in a retrospective study. All participants were treated with the FOLFIRI regimen until the disease progressed or an intolerable level of toxicity occurred.
In this study, three phenotypes of the UGT1A1 gene promoter were found: the homozygous wild type (TA6/6 type, 78.3%), the heterozygous mutant type (TA6/7 type, 19.6%), and the homozygous mutant type (TA7/7 type, 2.1%). Compared with TA6/7 and TA6/6, the risk of nonresponse to FOLFIRI chemotherapy increased by 16%, but the difference was not significant. The risk of death increased by 24%, and there was no significant difference. There was a risk of hematologic and nonhematologic adverse reactions occurring in TA6/7 and TA6/6, and the total risk of adverse reactions increased by 9.3773 times among patients with more than two metastatic organs. Compared with patients with TA6/6, the risk of toxic side-effects increased by 42.8066 times (
= 0.0259) for patients with TA6/7. Among patients who received FOLFIRI chemotherapy for more than four cycles, the proportion with TA6/7 was greater than that with TA6/6. Compared with those with TA6/6, patients with TA6/7 showed a higher risk of hematologic toxicity (22.3246 times,
= 0.0035).
The TA6/7 in patients with advanced colorectal cancer had more than two metastatic organs, and received FOLFIRI chemotherapy for more than four cycles compared with TA6/6 patients. Furthermore, the risk of hematologic and nonhematologic adverse reactions significantly increased, and the risk of digestive-tract and hematologic toxicity was more significant.</description><subject>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>Biological Variation, Population</subject><subject>Camptothecin - administration & dosage</subject><subject>Camptothecin - adverse effects</subject><subject>Camptothecin - analogs & derivatives</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>China - epidemiology</subject><subject>Colon cancer</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Colorectal Neoplasms - radiotherapy</subject><subject>Correlation of Data</subject><subject>Digestive System Diseases - chemically induced</subject><subject>Digestive System Diseases - diagnosis</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Drug-Related Side Effects and Adverse Reactions - genetics</subject><subject>Female</subject><subject>Fluorouracil - administration & dosage</subject><subject>Fluorouracil - adverse effects</subject><subject>Glucuronosyltransferase - genetics</subject><subject>Hematologic Diseases - chemically induced</subject><subject>Hematologic Diseases - diagnosis</subject><subject>Humans</subject><subject>Leucovorin - administration & dosage</subject><subject>Leucovorin - adverse effects</subject><subject>Male</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Mutants</subject><subject>Neoplasm Staging</subject><subject>Outcome and Process Assessment, Health Care</subject><subject>Patients</subject><subject>Phenotypes</subject><subject>Prognosis</subject><subject>Radiotherapy - methods</subject><subject>Retrospective Studies</subject><subject>Risk Assessment</subject><subject>Side effects</subject><subject>Toxicity</subject><subject>Uridine</subject><issn>1084-9785</issn><issn>1557-8852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kE1PAjEQhhujEUWPXk0Tz4v9oNvuEYkgCQnEwHnT7c7KkqXFdtFw8L_bDehlZjJ55p3kQeiBkgElKns2hR8wwshgSFN-gW6oEDJRSrDLOBM1TDKpRA_dhrAlhKQkldeox7mSMiPDG_Sz2gAeO--h0W3tLH6B9hvA4vV0RUcUT8ECXm7Auva4h4C1LXHbnTS1rY1u8NK7D-tCHbCr8Kj80tZAGRMb58G0ERh3G49HVRvrZDGfzN5nOH71en-8Q1eVbgLcn3sfrSevq_FbMl9MZ-PRPDGc0TYpTUqrFIaFYUVBuGTEgJJaxqUowVQGdCQoSZUyUqosSyvBRZHpjAtRFCXvo6dT7t67zwOENt-6g7fxZc5EJgVTjPJIJSfKeBeChyrf-3qn_TGnJO9k51F23snOO9mRfzynHoodlP_0n13-CzI2eiw</recordid><startdate>202111</startdate><enddate>202111</enddate><creator>Li, Xiao-Kai</creator><creator>Wang, Wen-Ling</creator><creator>Xu, Yu-Xuan</creator><creator>Yang, Yuan</creator><creator>Wang, Gang</creator><creator>Dong, Hong-Min</creator><creator>Chen, Wei-Wei</creator><creator>Li, Guo-Dong</creator><general>Mary Ann Liebert, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope></search><sort><creationdate>202111</creationdate><title>The Correlation Between UGT1A1 Gene Phenotypes and the Clinical Prognosis of Advanced Colorectal Cancer After FOLFIRI Therapy</title><author>Li, Xiao-Kai ; Wang, Wen-Ling ; Xu, Yu-Xuan ; Yang, Yuan ; Wang, Gang ; Dong, Hong-Min ; Chen, Wei-Wei ; Li, Guo-Dong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c321t-dc61f6e4bc2bb03720ce87a71f65decfceac6110688c778996f535b9a9355bbd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols - adverse effects</topic><topic>Biological Variation, Population</topic><topic>Camptothecin - administration & dosage</topic><topic>Camptothecin - adverse effects</topic><topic>Camptothecin - analogs & derivatives</topic><topic>Cancer therapies</topic><topic>Chemotherapy</topic><topic>China - epidemiology</topic><topic>Colon cancer</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Colorectal Neoplasms - radiotherapy</topic><topic>Correlation of Data</topic><topic>Digestive System Diseases - chemically induced</topic><topic>Digestive System Diseases - diagnosis</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Drug-Related Side Effects and Adverse Reactions - genetics</topic><topic>Female</topic><topic>Fluorouracil - administration & dosage</topic><topic>Fluorouracil - adverse effects</topic><topic>Glucuronosyltransferase - genetics</topic><topic>Hematologic Diseases - chemically induced</topic><topic>Hematologic Diseases - diagnosis</topic><topic>Humans</topic><topic>Leucovorin - administration & dosage</topic><topic>Leucovorin - adverse effects</topic><topic>Male</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Mutants</topic><topic>Neoplasm Staging</topic><topic>Outcome and Process Assessment, Health Care</topic><topic>Patients</topic><topic>Phenotypes</topic><topic>Prognosis</topic><topic>Radiotherapy - methods</topic><topic>Retrospective Studies</topic><topic>Risk Assessment</topic><topic>Side effects</topic><topic>Toxicity</topic><topic>Uridine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Xiao-Kai</creatorcontrib><creatorcontrib>Wang, Wen-Ling</creatorcontrib><creatorcontrib>Xu, Yu-Xuan</creatorcontrib><creatorcontrib>Yang, Yuan</creatorcontrib><creatorcontrib>Wang, Gang</creatorcontrib><creatorcontrib>Dong, Hong-Min</creatorcontrib><creatorcontrib>Chen, Wei-Wei</creatorcontrib><creatorcontrib>Li, Guo-Dong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Cancer biotherapy & radiopharmaceuticals</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Xiao-Kai</au><au>Wang, Wen-Ling</au><au>Xu, Yu-Xuan</au><au>Yang, Yuan</au><au>Wang, Gang</au><au>Dong, Hong-Min</au><au>Chen, Wei-Wei</au><au>Li, Guo-Dong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Correlation Between UGT1A1 Gene Phenotypes and the Clinical Prognosis of Advanced Colorectal Cancer After FOLFIRI Therapy</atitle><jtitle>Cancer biotherapy & radiopharmaceuticals</jtitle><addtitle>Cancer Biother Radiopharm</addtitle><date>2021-11</date><risdate>2021</risdate><volume>36</volume><issue>9</issue><spage>720</spage><epage>727</epage><pages>720-727</pages><issn>1084-9785</issn><eissn>1557-8852</eissn><abstract>This study investigated the correlations between the different phenotypes of the uridine diphosphate glucuronyl transferase (UGT) 1A1 gene and the treatment of advanced colorectal cancer after the FOLFIRI regimen.
A total of 240 advanced colorectal cancer patients with stage IV colon cancer or recurrence after radical surgery between January 2014 and December 2018 were included in a retrospective study. All participants were treated with the FOLFIRI regimen until the disease progressed or an intolerable level of toxicity occurred.
In this study, three phenotypes of the UGT1A1 gene promoter were found: the homozygous wild type (TA6/6 type, 78.3%), the heterozygous mutant type (TA6/7 type, 19.6%), and the homozygous mutant type (TA7/7 type, 2.1%). Compared with TA6/7 and TA6/6, the risk of nonresponse to FOLFIRI chemotherapy increased by 16%, but the difference was not significant. The risk of death increased by 24%, and there was no significant difference. There was a risk of hematologic and nonhematologic adverse reactions occurring in TA6/7 and TA6/6, and the total risk of adverse reactions increased by 9.3773 times among patients with more than two metastatic organs. Compared with patients with TA6/6, the risk of toxic side-effects increased by 42.8066 times (
= 0.0259) for patients with TA6/7. Among patients who received FOLFIRI chemotherapy for more than four cycles, the proportion with TA6/7 was greater than that with TA6/6. Compared with those with TA6/6, patients with TA6/7 showed a higher risk of hematologic toxicity (22.3246 times,
= 0.0035).
The TA6/7 in patients with advanced colorectal cancer had more than two metastatic organs, and received FOLFIRI chemotherapy for more than four cycles compared with TA6/6 patients. Furthermore, the risk of hematologic and nonhematologic adverse reactions significantly increased, and the risk of digestive-tract and hematologic toxicity was more significant.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>33877904</pmid><doi>10.1089/cbr.2020.4163</doi><tpages>8</tpages></addata></record> |
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| subjects | Antineoplastic Combined Chemotherapy Protocols - administration & dosage Antineoplastic Combined Chemotherapy Protocols - adverse effects Biological Variation, Population Camptothecin - administration & dosage Camptothecin - adverse effects Camptothecin - analogs & derivatives Cancer therapies Chemotherapy China - epidemiology Colon cancer Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - drug therapy Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology Colorectal Neoplasms - radiotherapy Correlation of Data Digestive System Diseases - chemically induced Digestive System Diseases - diagnosis Drug Resistance, Neoplasm - genetics Drug-Related Side Effects and Adverse Reactions - genetics Female Fluorouracil - administration & dosage Fluorouracil - adverse effects Glucuronosyltransferase - genetics Hematologic Diseases - chemically induced Hematologic Diseases - diagnosis Humans Leucovorin - administration & dosage Leucovorin - adverse effects Male Metastases Metastasis Middle Aged Mutants Neoplasm Staging Outcome and Process Assessment, Health Care Patients Phenotypes Prognosis Radiotherapy - methods Retrospective Studies Risk Assessment Side effects Toxicity Uridine |
| title | The Correlation Between UGT1A1 Gene Phenotypes and the Clinical Prognosis of Advanced Colorectal Cancer After FOLFIRI Therapy |
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