UGT1A1 Polymorphism Positive

3602 Background: 5-Fluorouracil plus CPT-11 is one of the standard 1st-line therapies in patients (pts) with metastatic colorectal cancer (MCRC). Although it has been reported that individuals carrying the (TA) 7 allele in the TATAA promoter of UGT1A1 increased risk of severe toxic event occurrence after CPT-11 administration, there is no report about phase I study based on the polymorphism of UGT1A1. Here we report the results from a genetic UGT1A1 polymorphism oriented phase I study of CPT-11 and 5’-DFUR to determine the maximum tolerated dose (MTD) and the recommend doses (RD) for each UGT1A1 genotypes. Methods: Eligibility criteria were as follows; histologically proven CRC with unresectable metastatic lesions, PS 0–2, age<76, adequate organ functions, and written informed consent. CPT-11 was infused (level 1, 2, 3 and 4: 70, 100, 120, 150 mg/m2, respectively) biweekly and 5’-DFUR was administered orally (800 mg/body, <1.39 m2; 600 mg/body) on 5 consecutive days with 2 days’ rest for more than 12 weeks. DLT were determined as grade 3 hematological and non-hematological toxicities. Genotypes were determined by analyzing the sequence of TATA box of UGT1A1 of genomic DNA from pts. Results: Eighteen pts with wild 6/6 allele and 9 pts with mutated 6/7 allele were registered. In pts with 6/6 allele, MTD was not observed up to level 4 (150 mg/m2). In pts with mutated 6/7 allele, on the other hand, MTD was observed at level 2 (100 mg/m2). We recommend doses of 70 mg/m2 of CPT-11 for pts with mutated 6/7 allele and 150 mg/m2 of CPT-11 for pts with wild 6/6 allele, respectively. Conclusions: The recommended phases II/III starting doses of biweekly CPT-11 administration are 150 mg/m2 for pts with wild 6/6 allele and 70 mg/m2 of CPT-11 for pts with mutated 6/7 allele, and 5’ -DFUR 800 mg/body on every 5 days per week. This combination therapy may be administered safely for all pts according to the TATAA promoter polymorphism of UGT1A1. The gene polymorphism should be taken into consideration to provide more precise information to guess the individual toxicities. No significant financial relationships to disclose.

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The usefulness of UGT1A1 polymorphism testing before starting irinotecan-based chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.11055 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 11055-11055

Author(s):

Taishi Harada ◽

Haruhiro Saito ◽

Makiko Sugiura ◽

Shuji Murakami ◽

Tetsuro Kondo ◽

...

Keyword(s):

Lung Cancer ◽

Enzyme Activity ◽

Adverse Events ◽

Elderly Patients ◽

Combination Chemotherapy ◽

Test Group ◽

Hematologic Toxicity ◽

Lung Cancer Patients ◽

Ugt1a1 Polymorphism ◽

Ugt1a1 Genotype

11055 Background: A few studies have revealed an association between UGT1A1 genotype and irinotecan-induced neutropenia. However, the usefulness of UGT1A1 polymorphism testing before starting irinotecan-based chemotherapy is controversial, even now. We assessed the clinical usefulness of UGT1A1 polymorphism testing before chemotherapy. Methods: 136 lung cancer patients were treated with nedaplatin and irinotecan combination chemotherapy as initial chemotherapy. Except for the patients with low enzyme activity of UGT1A1, 70 patients were treated after UGT1A1 polymorphism testing. (test group) 66 patients were treated without UGT1A1 polymorphism testing. (non-test group) We retrospectively analyzed adverse events and compared the test group with non-test group. Results: We could not confirm any reduction in hematologic or non-hematologic toxicity statistically in the test group. In 9 patients with non-hematologic toxicity of grade 4 and 5, 6 patients had febrile neutropenia (FN). All patients with FN were older than 70 years old. Adverse events in elderly patients were significantly more frequent than in the non-elderly. Conclusions: In patients treated with nedaplatin and irinotecan combination chemotherapy, UGT1A1 polymorphism testing before starting chemotherapy did not reduce adverse events. With UGT1A1 polymorphism testing only, it was difficult to predict the onset of severe adverse events. Therefore, it is more important to manage adverse events carefully, especially in elderly patients.

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UGT1A1 polymorphism has a prognostic effect in patients with stage IB or II uterine cervical cancer and one or no metastatic pelvic nodes receiving irinotecan chemotherapy

10.21203/rs.3.rs-27689/v3 ◽

2020 ◽

Author(s):

Hideki Matsuoka ◽

Ryusuke Murakami ◽

Kaoru Abiko ◽

Ken Yamaguchi ◽

Akihito Horie ◽

...

Keyword(s):

Cervical Cancer ◽

Side Effects ◽

Lymph Nodes ◽

Progression Free Survival ◽

Conditional Inference ◽

Free Survival ◽

Metastatic Lymph Nodes ◽

Ugt1a1 Polymorphism ◽

Metastatic Lymph ◽

Gynecology And Obstetrics

Abstract Background : Uridine diphosphate glucuronosyltransferase 1 family polypeptide A1 (UGT1A1 ) is a predictive biomarker for the side-effects of irinotecan; irinotecan chemotherapy reduces the volume of tumors harboring UGT1A1 polymorphisms. We aimed to determine whether UGT1A1 polymorphisms can predict progression-free survival in patients with local cervical cancer treated with irinotecan. Methods : We retrospectively analyzed the data of 51 patients with cervical cancer treated at a single institution between 2010 and 2015. All patients were diagnosed with the 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IB1, IB2, IIA, or IIB squamous cell carcinoma, underwent radical hysterectomy, and received irinotecan chemotherapy as neoadjuvant and/or adjuvant treatment. All patients were examined for irinotecan side effects using UGT1A1 tests. Conditional inference tree and survival analyses were performed considering stage, age, UGT1A1 status, and the number of metastatic lymph nodes to determine primary factors associated with progression-free survival. Results : The tree-structured survival model determined high recurrence-risk factors related to progression-free survival. The most relevant factor was ≥2 metastatic lymph nodes (p = 0.004). The second most relevant was UGT1A1 genotype (p = 0.024). Among patients with ≤1 metastatic lymph node, those with UGT1A1 polymorphisms benefited from irinotecan chemotherapy and demonstrated significantly longer progression-free survival (p = 0.020) than those with wild-type UGT1A1 . Conclusion : Irinotecan chemotherapy has the potential to benefit patients with cervical cancer, UGT1A1 polymorphism, and ≤1 metastatic lymph nodes.

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Association between UGT1A1 Polymorphism and Risk of Laryngeal Squamous Cell Carcinoma

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph13010112 ◽

2016 ◽

Vol 13 (1) ◽

pp. 112 ◽

Cited By ~ 4

Author(s):

Hui Huangfu ◽

Hong Pan ◽

Binquan Wang ◽

Shuxin Wen ◽

Rui Han ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Ugt1a1 Polymorphism

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UGT1A1 polymorphism as a prognostic indicator of stage I ovarian clear cell carcinoma patients treated with irinotecan

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyw163 ◽

2016 ◽

Vol 47 (2) ◽

pp. 170-174 ◽

Cited By ~ 1

Author(s):

Tomoko Yoshihama ◽

Akira Hirasawa ◽

Hiroyuki Nomura ◽

Tomoko Akahane ◽

Yoshiko Nanki ◽

...

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Prognostic Indicator ◽

Stage I ◽

Ovarian Clear Cell Carcinoma ◽

Ugt1a1 Polymorphism

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SERUM TOTAL BILIRUBIN, NOT CHOLELITHIASIS, IS INFLUENCED BY UGT1A1 POLYMORPHISM, ALPHA THALASSEMIA AND S GENOTYPE: FIRST REPORT ON COMPARISON BETWEEN ARAB-INDIAN AND AFRICAN S GENES

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2015.060 ◽

2015 ◽

Vol 7 ◽

pp. e2015060 ◽

Cited By ~ 4

Author(s):

Said Y ALkindi ◽

Anil Pathare ◽

Salam Alkindi

Keyword(s):

Steady State ◽

Bilirubin Level ◽

Total Bilirubin ◽

Globin Gene ◽

Total Bilirubin Level ◽

Promoter Polymorphism ◽

Serum Total Bilirubin ◽

Imaging Data ◽

Ugt1a1 Polymorphism ◽

The Mean

Background: We explored the potential relationship between steady state serum bilirubin levels and the incidence of cholelithiasis in the context of UGT1A1 gene A(TA)nTAA promoter polymorphism in Omani sickle cell anemia (SCA) patients, homozygotes for African (Benin and Bantu) and Arab-Indian bS haplotypes, but sharing the same microgeographical environment and comparable life style factors. Methods: 136 SCA patients were retrospectively studied in whom imaging data including abdominal CT scan, MRI or Ultrasonography was routinely available. Available data on the mean steady state hematological/biochemical parameters (n=136), bs haplotypes(n=136), a globin gene status (n=105) and UGT1A1 genotypes(n=133) were reviewed from the respective medical records. Results: The mean serum total bilirubin level was significantly higher in the homozygous UGT1A1(AT)7 group as compared to UGT1A1(AT)6 group. Strikingly, cholelithiasis was not influenced by age, gender, alpha globin genotype or bS haplotypes in this SCA cohort. Conclusion: As observed in other population groups, the UGT1A1 (AT)7 homozygosity was significantly associated with raised serum total bilirubin level, but the prevalence of gallstones in the Omani SCA patients was not associated with a thalassaemia, UGT1A1 polymorphism, or bs haplotypes.

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Pharmacogenetic study in Hodgkin lymphomas reveals the impact of UGT1A1 polymorphisms on patient prognosis

Blood ◽

10.1182/blood-2008-03-148874 ◽

2009 ◽

Vol 113 (14) ◽

pp. 3307-3313 ◽

Cited By ~ 29

Author(s):

Vincent Ribrag ◽

Serge Koscielny ◽

Olivier Casasnovas ◽

Cecile Cazeneuve ◽

Pauline Brice ◽

...

Keyword(s):

Treatment Failure ◽

Hodgkin Lymphoma ◽

Gene Polymorphisms ◽

Peripheral Blood Lymphocytes ◽

Pharmacogenetic Study ◽

Time To Treatment ◽

Ugt1a1 Polymorphism ◽

Hodgkin Lymphoma Patient ◽

Time To Treatment Failure ◽

The Impact

AbstractHodgkin lymphoma is a highly curable malignancy, but treatment outcome might be influenced by inherited gene polymorphisms determining anticancer agent metabolism. We prospectively collected peripheral blood lymphocytes from 313 patients with Hodgkin lymphomas to analyze GSTP1, GSTM1, GSTT1, UGT1A1, and CYP3A4 enzyme gene polymorphisms. All patients were treated with chemotherapy, associated with radiotherapy when they had localized disease. There was no difference for GSTP1, GSTM1, and GSTT1 as well as for UGT1A1 and CYP3A4 polymorphism distributions between Hodgkin lymphoma patients and healthy controls. Patients carrying 1 or 2 UGT1A1*28 allele had a significantly (P < .05) better freedom from progression and time to treatment failure than those homozygous for the UGT1A1 TA6/TA6 allele. Multivariate prognostic analyses showed that the UGT1A1 polymorphism was as an independent prognostic parameter for all the studied endpoints, the wild-type homozygous UGT1A1 TA6/TA6 genotype being associated with a significantly worse prognosis than genotypes with at least one UGT1A1*28 allele (overall survival; relative risk [RR] = 2.54, 95% confidence interval [CI], 1.05-6.14; P = .04; freedom from progression, RR = 2.70, 95% CI, 1.37-5.31; P = .004; time to treatment failure, RR = 2.37, 95% CI, 1.28-4.40, P = .006). UGT1A1 polymorphism on TA repeats, which are thought to determine several anticancer drugs metabolism, influence Hodgkin lymphoma patient outcome.

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