scholarly journals UGT1A1 gene polymorphism: Impact on toxicity and efficacy of irinotecan-based regimens in metastatic colorectal cancer

2009 ◽  
Vol 15 (40) ◽  
pp. 5058 ◽  
Author(s):  
Christoph Schulz ◽  
Volker Heinemann ◽  
Andreas Schalhorn ◽  
Nikolas Moosmann ◽  
Thomas Zwingers ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Polymorphism ◽  
Metastatic Colorectal Cancer ◽  
Ugt1a1 Gene

scholarly journals Correlation between UGT1A1 gene polymorphism and irinotecan chemotherapy in metastatic colorectal cancer：a study from Guangxi Zhuang

2020 ◽  
Author(s):  
Shaojun Chen ◽  
Li Hua ◽  
Chenjun Feng ◽  
Qia Mo ◽  
Mengzhuan Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Polymorphism ◽  
Metastatic Colorectal Cancer ◽  
Heterozygous Mutation ◽  
Wild Type ◽  
Ugt1a1 Gene ◽  
Geographical Regions ◽  
Significant Difference ◽  
Homozygous Mutant ◽  
Grade 3

Abstract Background: UGTlA1 gene polymorphism has different distribution in different ethnicities, geographical regions and ethnic groups, which may lead to different toxicity and efficacy of irinotecan. The study aimed to explore the correlation of UGT1A1 gene polymorphism of Guangxi Zhuang metastatic colorectal cancer (mCRC) with irinotecan -based chemotherapy, in order to develop an individualized irinotecan regimen for mCRC patients of Guangxi Zhuang. Methods: From June 2013 and June 2015, a total of 406 patients of Guangxi who were histologically diagnosed as metastatic colorectal cancer with 102 patients of this cohort with three generations of Zhuang, and 86 patients that conformed to inclusion and exclusion criteria were competitively enrolled . The distribution of UGT1A1 gene polymorphism was analyzed-retrospectively in all patients. Pyrosequencing method was used to detect the UGT1A1 * 28 and * 6 gene polymorphism in the 86 Guangxi Zhuang mCRC patients. After first-line chemotherapy with FOLFIRI regimen, the relationship between gene polymorphism of UGT1A1 and adverse reactions, and efficacy of Irinotecan were analyzed with χ2 test and Kaplan-Meier method.Results: UGT1A1 * 28 wild-type (TA6 / 6), heterozygous mutant (TA6 /7) and homozygous mutant (TA7 / 7) accounted for 69.8%, 30.2% and 0%, respectively. UGT1A1 * 6 wild type (G / G), heterozygous mutation type (G / A) and homozygous mutant (A / A) accounted for 76.7%，20.9% and 2.3%，respectively.UGT1A1 * 28 TA6 / 7 type could increase the risk of grade 3-4 diarrhea (P=0.027), which did not increase the risk of grade 3-4 neutropenia (P=0.092). UGT1A1 * 6 G / A and A / A type could increase the risk of grade 3-4 diarrhea and neutropenia (P=0.001; P=0.017). After chemotherapy with FOLFIRI, there was no significant difference in response rate (RR) (P=0.729; P=0.745) or in median progression-free survival (mPFS) between the wild-type, mutant treatment of UGT1A1 * 28 and UGT1A1 * 6 (7.0 m vs 7.4 m, P=0.427; 6.9 m vs 7.0m P=0.408).Conclusions: The distribution of UGT1A1*28 and UGT1A1* 6 gene polymorphism in Guangxi Zhuang patients were differed from the existing reported of European people and Chinese Han population. The UGT1A1 gene polymorphism with irinotecan chemotherapy-associated diarrhea and neutropenia were closely related. There was no significant association between UGT1A1 gene polymorphism and therapeutic efficacy of irinotecan.

scholarly journals Correlation between UGT1A1 gene polymorphism and irinotecan chemotherapy in metastatic colorectal cancer: a study from Guangxi Zhuang

2020 ◽  
Author(s):  
Shaojun Chen ◽  
Li Hua ◽  
Chenjun Feng ◽  
Qia Mo ◽  
Mengzhuan Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Polymorphism ◽  
Metastatic Colorectal Cancer ◽  
Heterozygous Mutation ◽  
Wild Type ◽  
Ugt1a1 Gene ◽  
Geographical Regions ◽  
Significant Difference ◽  
Homozygous Mutant ◽  
Grade 3

Abstract Background: UGTlA1 gene polymorphism has different distribution in different ethnicities, geographical regions and ethnic groups, which may lead to different toxicity and efficacy of irinotecan. The study aimed to explore the correlation of UGT1A1 gene polymorphism of Guangxi Zhuang metastatic colorectal cancer (mCRC) with irinotecan -based chemotherapy to develop an individualized irinotecan regimen. Methods: From June 2013 and June 2015, a total of 406 patients of Guangxi who were histologically diagnosed as metastatic colorectal cancer and 86 patients of this with three generations of Zhuang who were accorded with inclusion and exclusion criteria were enrolled. The distribution of UGT1A1 gene polymorphism was analyzed retrospectively in all patients. Pyrosequencing method was used to detect the UGT1A1 * 28 and * 6 gene polymorphism in the 86 Guangxi Zhuang mCRC patients. After first-line chemotherapy with FOLFIRI regimen, the relationship between gene polymorphism of UGT1A1 and adverse reactions, and efficacy of Irinotecan were analyzed with χ2 test and Kaplan-Meier method. Results: UGT1A1 * 28 wild-type (TA6 / 6), heterozygous mutant (TA6 /7) and homozygous mutant (TA7 / 7) accounted for 69.8%, 30.2%and 0%, respectively. UGT1A1 * 6 wild type (G / G), heterozygous mutation type (G / A) and homozygous mutant (A / A) accounted for 76.7% ，20.9%and 2.3%，respectively。UGT1A1 * 28 TA6 / 7 type could increase the risk of grade 3-4 diarrhea (P=0.027), which did not increase the risk of grade 3-4 neutropenia (P=0.092). UGT1A1 * 6 G / A and A / A type could increase the risk of grade 3-4 diarrhea and neutropenia (P=0.001; P=0.017). After chemotherapy with FOLFIRI, there was no significant difference in response rate (RR) (P=0.729; P=0.745). The median progression-free survival (mPFS) between the wild-type, mutant treatment of UGT1A1 * 28 and UGT1A1 * 6 (7.0m vs 7.4 m, P=0.427; 6.9mvs 7.0m P=0.408). Conclusions: The distribution of UGT1A1*28 and UGT1A1* 6 gene polymorphism in Guangxi Zhuang patients were differed from the existing reported of European people,Chinese Han population. The UGT1A1 gene polymorphism with irinotecan chemotherapy-associated diarrhea and neutropenia were closely related. There was no significant association between UGT1A1 gene polymorphism and therapeutic efficacy of irinotecan.

scholarly journals Correlation between UGT1A1 gene polymorphism and irinotecan chemotherapy in metastatic colorectal cancer：a study from Guangxi Zhuang

2020 ◽  
Author(s):  
Shaojun Chen ◽  
Li Hua ◽  
Chenjun Feng ◽  
Qia Mo ◽  
Mengzhuan Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Polymorphism ◽  
Metastatic Colorectal Cancer ◽  
Heterozygous Mutation ◽  
Wild Type ◽  
Chinese Han ◽  
Ugt1a1 Gene ◽  
Significant Difference ◽  
Homozygous Mutant ◽  
Grade 3

Abstract Background: There are obviously ethnic differences between the UGT1A1 gene polymorphisms.Due to the difference of genetic background and environment,the treatment with colorectal cancer patients of Guangxi Zhuang should not completely follow the Euramerican or Chinese han patients.The study aimed to explore the correlation of UGT1A1 gene polymorphism of Guangxi Zhuang metastatic colorectal cancer (mCRC) with irinotecan -based chemotherapy, in order to develop an individualized irinotecan regimen for mCRC patients of Guangxi Zhuang. Methods: From June 2013 and June 2015, a total of 406 patients of Guangxi who were histologically diagnosed as metastatic colorectal cancer with 86 patients that conformed to inclusion and exclusion criteria were competitively enrolled.The distribution of UGT1A1 gene polymorphism was analyzed-retrospectively in all patients. Pyrosequencing method was used to detect the UGT1A1 *28 and*6 gene polymorphism in the 86 Guangxi Zhuang mCRC patients. After first-line chemotherapy with FOLFIRI regimen, the relationship between gene polymorphism of UGT1A1 and adverse reactions, and efficacy of Irinotecan were analyzed with χ2 test and Kaplan-Meier method. Results: UGT1A1 *28 wild-type (TA6/6), heterozygous mutant (TA6/7) and homozygous mutant (TA7/7) accounted for 69.8%, 30.2% and 0%, respectively. UGT1A1 *6 wild type (G / G), heterozygous mutation type (G / A) and homozygous mutant (A / A) accounted for 76.7%，20.9% and 2.3%，respectively. UGT1A1 *28 TA6 / 7 type could increase the risk of grade 3~4 diarrhea (p=0.027), which did not increase the risk of grade 3~4 neutropenia (p=0.092). UGT1A1 *6 G / A and A / A type could increase the risk of grade 3~4 diarrhea and neutropenia (p=0.001; p=0.017). After chemotherapy with FOLFIRI, there was no significant difference in response rate (RR) (p=0.729; p=0.745) or in median progression-free survival (mPFS) between the wild-type, mutant treatment of UGT1A1 *28 and UGT1A1 *6 (7.0m vs 7.4m, p=0.427; 6.9m vs 7.0m p=0.408). Conclusions: The distribution of UGT1A1 *28 and UGT1A1 *6 gene polymorphism in Guangxi Zhuang patients were differed from the existing reported of European people and Chinese Han population. The UGT1A1 gene polymorphism with irinotecan chemotherapy-associated diarrhea and neutropenia were closely related. There was no significant association between UGT1A1 gene polymorphism and therapeutic efficacy of irinotecan.

scholarly journals UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer

2004 ◽  
Vol 91 (4) ◽  
pp. 678-682 ◽  
Author(s):  
E Marcuello ◽  
A Altés ◽  
A Menoyo ◽  
E del Rio ◽  
M Gómez-Pardo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Ugt1a1 Gene

scholarly journals CORRELATION ANALYSIS OF GSTP1 GENE POLYMORPHISM WITH MORBIDITY OF PRIMARY METASTATIC COLORECTAL CANCER

2020 ◽  
Vol 2 ◽  
pp. 25-31
Author(s):  
Yuri Bazhora ◽  
Sergii Chetverikov ◽  
Viacheslav Onyshchenko ◽  
Mykhailo Chetverikov ◽  
Valeriia Chetverikova-Ovchynnyk
Keyword(s):  
Colorectal Cancer ◽  
Correlation Analysis ◽  
Gene Polymorphism ◽  
Metastatic Colorectal Cancer ◽  
Glutathione Transferase ◽  
Control Group ◽  
Healthy Population ◽  
Glutathione S Transferase ◽  
Pathological Conditions ◽  
Gstp1 Gene

Colorectal cancer (CRC) is one of the most common malignancies. Susceptibility to malignant processes is mediated by genetically driven differences in the effectiveness of detoxification of potential carcinogens. One of the factors that may influence the risk of CRC is the glutathione-S-transferase (GST) gene family that encodes glutathione transferase enzymes. The GSTP1 gene is expressed both in normal and pathological conditions. Determining its specific alleles may be a marker of CRC. The aim of the research – to study GSTP1 gene polymorphism, which is likely to be more common among patients with primary metastatic colorectal cancer compared with healthy population. Materials and methods. The study involved 12 patients with primary metastatic colorectal cancer aged 43 to 72 years, the control group was represented by a sample of 31 people without cancer. Results. The incidence of advanced CRC in the presence of GSPT1 Val / Val (aa) polymorphism is statistically significantly higher than in the presence of Ile / Ile (AA) and Ile / Val (Aa) GSPT1 polymorphism. Conclusions. Among people with GSTP1 Val / Val (aa) polymorphism, primary CRC is 4.4 times more likely than among people with GSPT1 Ile / Ile (AA) and Ile / Val (Aa) polymorphisms, which are statistically significant (P < 0.05). The obtained results indicate the possibility of conducting a genetic study of GSTP1 polymorphism to form groups of potential risk of CRC.

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