Association between UGT1A1*28 Gene Polymorphism and Severe Neutropenia due to Colorectal Cancer Treatment with Irinotecan: Evidence Based on Meta-Analysis

Abstract Objective The present study aimed to evaluate the relationship between UGT1A1*28 gene polymorphism and the prevalence of neutropenia in patients with colorectal cancer treated with irinotecan. Method Thirteen studies were included. These papers were selected from the Virtual Health Library, Scientific Electronic Library Online, International Health Sciences Literature and PubMed, and their data were collected and evaluated using the BioEstat 5.3 software (BioEstat, Belém, PA, Brazil). Results Three genotypes were analyzed, namely 6/6 (wild type), 6/7, and 7/7. In total, 2,146 patients were included in the present study; of these, 55.6% (n = 1,193) had 6/6 genotype, 37.3% (n = 801) were heterozygous (6/7), and 7.1% (n = 152) had the 7/7 genotype. A total of 1,672 (77.9%) patients displayed mild neutropenia, whereas 474 (22.1%) had severe neutropenia. When contrasting the 6/7 and 7/7 genotypes with the 6/6 genotype using statistical tests for meta-analysis, patients with the 7 allele, either in homozygosis or heterozygosis, presented higher risk of developing severe neutropenia than patients with the 6/6 genotype (odds ratio = 1.559; 95% confidence interval = 1.163–2.090; p = 0.003). Conclusion The analysis of the UGT1A1*28 gene polymorphism can aid the choice of treatment for patients with colorectal cancer in personalized medicine, increasing the chances of therapeutic success.

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A trial sequential meta-analysis of TNF-α –308G>A (rs800629) gene polymorphism and susceptibility to colorectal cancer

Bioscience Reports ◽

10.1042/bsr20181052 ◽

2019 ◽

Vol 39 (1) ◽

Cited By ~ 1

Author(s):

Raju K. Mandal ◽

Munawwar Ali Khan ◽

Arif Hussain ◽

Naseem Akhter ◽

Arshad Jawed ◽

...

Keyword(s):

Colorectal Cancer ◽

Gene Polymorphism ◽

Meta Analysis ◽

Asian Population ◽

Epidemiological Studies ◽

Pooled Analysis ◽

Asian Ethnicity ◽

Tnf Α ◽

Factor Α ◽

The Relationship

Abstract Purpose: Tumor necrosis factor-α (TNF-α), secreted by the activated macrophages, may participate in the onset and progression of colorectal cancer (CRC). The association of TNF-α –308 G>A (rs1800629) single-nucleotide polymorphism (SNP) with CRC risk has been investigated by many studies but the results are inconclusive. A trial sequential meta-analysis was performed for precise estimation of the relationship between TNF-α –308 G>A gene polymorphism with CRC risk. Methods: Medline (PubMed), EMBASE (Excerpta-Medica) and Google Scholar were mined for relevant articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the significance of association. Results: The pooled analysis indicated no risk associated with TNF-α –308 G>A SNP and overall CRC risk in five genetic comparison models, i.e. allelic (A vs. G: P = 0.524; OR = 1.074, 95% CI = 0.863–1.335), homozygous (AA vs. GG: P = 0.489; OR = 1.227, 95% CI = 0.688–2.188), heterozygous (AG vs. GG: P = 0.811; OR = 1.024, 95% CI = 0.843–1.244), dominant (AA+AG vs. GG: P = 0.630; OR = 1.055, 95% CI = 0.849–1.311) and recessive (AA vs. AG+GG: P = 0.549; OR = 1.181, 95% CI = 0.686–2.033). Subgroup analysis revealed that TNF-α –308 G>A SNP is associated with reduced risk of CRC in Asian ethnicity. The study showed no publication bias. Conclusions: No association of TNF-α –308 G>A SNP with overall CRC risk was found. This SNP is likely to be protective against CRC in Asian population when compared with Caucasian population. Larger prospective-epidemiological studies are warranted to elucidate the roles of TNF-α –308 G>A SNP in the etiology of CRC and to endorse the present findings.

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The Relationship between Telomerase Activity and Clinicopathological Parameters in Colorectal Cancer: A Meta-Analysis

Balkan Medical Journal ◽

10.5152/balkanmedj.2015.151182 ◽

2016 ◽

Vol 33 (1) ◽

pp. 64-71 ◽

Cited By ~ 2

Author(s):

Xue Cheng Xie ◽

Lian Ying Ge ◽

Hao Lai ◽

Hai Qiu ◽

Fan Tang ◽

...

Keyword(s):

Colorectal Cancer ◽

Meta Analysis ◽

Telomerase Activity ◽

Clinicopathological Parameters ◽

The Relationship

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Systematic Review and Meta-Analysis of the Relationship between EPHX1 Polymorphisms and Colorectal Cancer Risk

PLoS ONE ◽

10.1371/journal.pone.0043821 ◽

2012 ◽

Vol 7 (8) ◽

pp. e43821 ◽

Cited By ~ 21

Author(s):

Fei Liu ◽

Ding Yuan ◽

Yonggang Wei ◽

Wentao Wang ◽

Lvnan Yan ◽

...

Keyword(s):

Colorectal Cancer ◽

Systematic Review ◽

Cancer Risk ◽

Meta Analysis ◽

Colorectal Cancer Risk ◽

The Relationship

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Cyp2C19*2 Polymorphism Related to Clopidogrel Resistance in Patients With Coronary Heart Disease, Especially in the Asian Population: A Systematic Review and Meta-Analysis

Frontiers in Genetics ◽

10.3389/fgene.2020.576046 ◽

2020 ◽

Vol 11 ◽

Author(s):

Ying Sun ◽

Qing Lu ◽

Xuefei Tao ◽

Biao Cheng ◽

Guoxing Yang

Keyword(s):

Gene Polymorphism ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Asian Population ◽

Fixed Effect Model ◽

Clopidogrel Resistance ◽

Effect Model ◽

The Relationship ◽

Allele Model

In recent years, the relationship between Cyp2C19*2 gene polymorphism and clopidogrel resistance reflected by platelet function assay has been studied extensively, but there is no clear conclusion yet. In order to evaluate the relationship between Cyp2C19*2 gene polymorphism and clopidogrel resistance more accurately, meta-analysis was conducted in this study. The I2 value taking 50% as the limit, the heterogeneity is judged as high or low, and then a random effect model or a fixed effect model is selected for statistical analysis. PubMed, EMBASE, Web of Science, CNKI, and China Wanfang database were searched, and the related literatures from the establishment of the database to May 2020 were collected and analyzed by STATA 15.0 software. A total of 3,073 patients were involved in 12 studies, including 1,174 patients with clopidogrel resistance and 1,899 patients with non-clopidogrel resistance. The results of this study showed that allele model (A vs. G): OR = 2.42 (95%CI: 1.97–2.98); dominant model (AA+GA vs. GG): OR = 2.74 (95%CI: 2.09–3.59); recessive model (AA vs. GA+GG): OR = 4.07 (95%CI: 3.06–5.41); homozygous model (AA vs. GG): OR = 5.70 (95%CI: 4.22–7.71); heterozygote model (GA vs. GG): OR = 2.32 (95%CI: 1.76–3.07), the differences were statistically significant. Also, the analysis of the Ethnicity subgroup indicated that the Asian allele model and the other four gene models were statistically significant. In conclusion, Cyp2C19*2 gene polymorphism is strongly associated with clopidogrel resistance. Allele A, genotype GA, AA, and GG + GA can increase clopidogrel resistance, especially in the Asian population.

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Association of dietary fibre intake and gut microbiota in adults

British Journal Of Nutrition ◽

10.1017/s0007114518002465 ◽

2018 ◽

Vol 120 (9) ◽

pp. 1014-1022 ◽

Cited By ~ 20

Author(s):

Daniel Lin ◽

Brandilyn A. Peters ◽

Charles Friedlander ◽

Hal J. Freiman ◽

James J. Goedert ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Risk ◽

Gut Microbiota ◽

Dietary Fibre ◽

Meta Analysis ◽

Microbiota Composition ◽

Fibre Intake ◽

Dietary Fibre Intake ◽

The Relationship ◽

Gut Microbiota Composition

AbstractIncreasing evidence indicates that gut microbiota may influence colorectal cancer risk. Diet, particularly fibre intake, may modify gut microbiota composition, which may affect cancer risk. We investigated the relationship between dietary fibre intake and gut microbiota in adults. Using 16S rRNA gene sequencing, we assessed gut microbiota in faecal samples from 151 adults in two independent study populations: National Cancer Institute (NCI), n 75, and New York University (NYU), n 76. We calculated energy-adjusted fibre intake based on FFQ. For each study population with adjustment for age, sex, race, BMI and smoking, we evaluated the relationship between fibre intake and gut microbiota community composition and taxon abundance. Total fibre intake was significantly associated with overall microbial community composition in NYU (P=0·008) but not in NCI (P=0·81). In a meta-analysis of both study populations, higher fibre intake tended to be associated with genera of class Clostridia, including higher abundance of SMB53 (fold change (FC)=1·04, P=0·04), Lachnospira (FC=1·03, P=0·05) and Faecalibacterium (FC=1·03, P=0·06), and lower abundance of Actinomyces (FC=0·95, P=0·002), Odoribacter (FC=0·95, P=0·03) and Oscillospira (FC=0·96, P=0·06). A species-level meta-analysis showed that higher fibre intake was marginally associated with greater abundance of Faecalibacterium prausnitzii (FC=1·03, P=0·07) and lower abundance of Eubacterium dolichum (FC=0·96, P=0·04) and Bacteroides uniformis (FC=0·97, P=0·05). Thus, dietary fibre intake may impact gut microbiota composition, particularly class Clostridia, and may favour putatively beneficial bacteria such as F. prausnitzii. These findings warrant further understanding of diet–microbiota relationships for future development of colorectal cancer prevention strategies.

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Pharmacogenetic analysis of TS and UGT1A polymorphisms predictive for response and toxicity in Spanish patients with advanced colorectal cancer treated with first-line irinotecan and 5-fluorouracil

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4066 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 4066-4066

Author(s):

E. Martinez-Balibrea ◽

A. Abad ◽

M. Valladares ◽

M. Martinez-Villacampa ◽

E. Aranda ◽

...

Keyword(s):

Colorectal Cancer ◽

Advanced Colorectal Cancer ◽

Cox Regression ◽

Statistical Tests ◽

Severe Neutropenia ◽

High Dose ◽

Severe Toxicity ◽

First Line ◽

Severe Diarrhea ◽

Line Chemotherapy

4066 Background: The possible role of uridine diphosphate-glucuronosyltransferase 1A (UGT1A) and Thymidylate Synthase (TS) gene polymorphisms in predicting toxicity and outcomes in irinotecan/ 5-Fluorouracil (5FU)-treated patients is still controversial. The aim of this work was to determine whether UGT1A1, UGT1A7, and UGT1A9 as well as TS polymorphisms affect toxicities and/or outcomes of Spanish patients with advanced colorectal cancer (mCRC) Methods: A total of 149 patients with mCRC were treated either with weekly irinotecan plus high-dose 5FU (FUIRI) or biweekly irinotecan plus 5FU/Leucovorin (FOLFIRI) as first-line chemotherapy (Aranda E; Ann Oncol. 2008 Aug 20). Genomic DNA was extracted from peripheral blood and genotyped using allelic discrimination and direct sequencing. Chi-square test, Fisher's exact test and logistic regression were used to study the association of genotypes with toxicity and response. Log rank and cox regression were used in survival analysis. All statistical tests were two-sided. Results: According to TS 5’TRP genotypes, 79.3% of the 2R/2R patients responded to therapy while only 52.5% of 2R/3R or 3R/3R patients do so (HR=3.5; 95% CI=1.3- 9.1; p=0.009). TS genotypes were not associated with toxicity. UGT1A1*28 TA7/TA7 genotype was clearly associated with severe toxicity (HR=12.7; 95% CI=3.1–51.3; p=0.001) and diarrhea (HR=4; 95% CI=1.3–12; p=0.016) when compared to TA6/TA7 and TA6/TA6 genotypes. These patients also experienced more severe neutropenia (40% vs. 18.8%, p=0.087) and more frequent dose reductions (53.3% vs. 38.1%, p=ns). UGT1A7*3/*3 and UGT1A9–118(dT)9/9 were associated with severe diarrhea (50% vs. 27% p=0.032 and 43% vs. 23% p=0.012). When all non-favourable genotypes (TA7/TA7, *3/*3 and 9/9) were taken into account, there was a statistically significant association with severe diarrhea (HR=4.5; 95% CI 1.3–16.3; p=0.021), neutropenia (HR=3.5; 95% CI=1–12.7; p=0.047) and both (HR=12.4; 95% CI=2.8–54.2; p=0.001). Conclusions: Our data clearly link UGT1A genotypes with irinotecan-related severe toxicity. TS 5’TRP genotypes are predictive of response to irinotecan/5FU first-line chemotherapy. No significant financial relationships to disclose.

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