Dataset Information

HLA Polymorphisms And TKI-Induced Liver Injury in Patients with Cancer: A Meta-analysis.

ABSTRACT: Background: Tyrosine kinase inhibitors (TKIs) are widely used for patients with cancer, although liver injury has been observed in a small proportion of these patients. The aim of this study was to investigate the mechanisms underlying TKI-induced liver injury according to HLA polymorphisms. Methods: We systematically searched three electronic databases (PubMed, PMC, EmBase, and the Cochrane library) to identify studies that evaluated the impact of HLA polymorphisms on the incidence of TKI-induced liver injury in cancer patients as of November 2018. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Further, sensitivity analysis and publication bias assessments were also performed. Results: In the final analysis, four studies that involved a total of 12,181 patients were included. Three of the studies included patients who received lapatinib, and the other study included patients who received pazopanib. Overall, carriers of HLA-DQA1*02:01 were associated with an increased risk of liver injury (OR: 6.85; 95%CI: 2.34-20.02; P<0.001). Furthermore, HLA-DQB1*02:02 was correlated with a greater risk of liver injury (OR: 5.61; 95%CI: 2.80-11.25; P<0.001). Finally, HLA-DRB1*07:01 was significantly correlated with a greater risk of liver injury (OR: 4.06; 95%CI: 2.33-7.09; P<0.001). Conclusions: The findings of this meta-analysis confirmed that three polymorphisms of HLA were significantly associated with an increased risk of TKI-induced liver injury. Further work will be required to determine these relationships in patients with specific characteristics.

SUBMITTER: Xiang Q

PROVIDER: S-EPMC6584402 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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HLA Polymorphisms And TKI-Induced Liver Injury in Patients with Cancer: A Meta-analysis.

Xiang Qian Q Zhang Zhuo Z Wu Yingchao Y Zuo Shuai S Liu Qianxin Q Liu Tao T Wang Xin X Cui Yimin Y

Journal of Cancer 20190521 10

<b>Background</b>: Tyrosine kinase inhibitors (TKIs) are widely used for patients with cancer, although liver injury has been observed in a small proportion of these patients. The aim of this study was to investigate the mechanisms underlying TKI-induced liver injury according to HLA polymorphisms. <b>Methods</b>: We systematically searched three electronic databases (PubMed, PMC, EmBase, and the Cochrane library) to identify studies that evaluated the impact of HLA polymorphisms on the incidenc ...[more]

PMID: 31258719

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Project description:BackgroundPolygonum multiflorum is one of the leading causes of herb-induced liver injury in China. HLA-B*35:01 is reported to be a potential biomarker of Polygonum multiflorum-induced liver injury (PM-DILI). However, little is known about the relationship between single-nucleotide polymorphisms (SNPs) and PM-DILI.AimTo identify SNPs that indicate susceptibility to PM-DILI.MethodsWe conducted a systematic study enrolling 382 participants from four independent hospitals, including 73 PM-DILI patients, 118 patients with other drug-induced liver injury (other-DILI) and 191 healthy controls. Whole-exome sequencing was performed for 8 PM-DILI patients and 8 healthy controls who were randomly selected from the above subjects. Nineteen SNPs that showed high frequencies in the 8 PM-DILI patients were selected as candidate SNPs and then screened in 65 PM-DILI patients, 118 other-DILI patients and 183 healthy controls using the MassARRAY system. HLA-B high-resolution genotyping was performed for the 73 PM-DILI and 118 other-DILI patients. The Han-MHC database was selected as a population control for HLA-B analysis. P < 6.25 × 10-3 after Bonferroni correction was considered significant.ResultsThe frequencies of rs111686806 in the HLA-A gene, rs1055348 in the HLA-B gene, and rs202047044 in the HLA-DRB1 gene were significantly higher in the PM-DILI group than in the control group [27.2% vs 11.6%, P = 1.72 × 10-5, odds ratio (OR) = 3.96, 95% confidence interval (CI): 2.21-7.14; 42.5% vs 8.6%, P = 1.72 × 10-19, OR = 13.62, 95%CI: 7.16-25.9; 22.9% vs 8.1%, P = 4.64 × 10-6, OR = 4.1, 95%CI: 2.25-7.47]. Only rs1055348 showed a significantly higher frequency in the PM-DILI group than in the other-DILI group (42.5% vs 13.6%, P = 1.84 × 10-10, OR = 10.06, 95%CI: 5.06-20.0), which suggested that it is a specific risk factor for PM-DILI. rs1055348 may become a tag for HLA-B*35:01 with 100% sensitivity and 97.7% specificity in the PM-DILI group and 100% sensitivity and 98.1% specificity in the other-DILI group. Furthermore, HLA-B*35:01 was confirmed to be associated with PM-DILI with a frequency of 41.1% in the PM-DILI group compared with 11.9% (P = 4.30 × 10-11, OR = 11.11, 95%CI: 5.57-22.19) in the other-DILI group and 2.7% (P = 6.22 × 10-166, OR = 62.62, 95%CI: 35.91-109.20) in the Han-MHC database.Conclusionrs111686806, rs1055348, and rs202047044 are associated with PM-DILI, of which, rs1055348 is specific to PM-DILI. As a tag for HLA-B*35:01, rs1055348 may become an alternative predictive biomarker of PM-DILI.

Project description:Potential correlation of human papillomavirus (HPV) 16 E6 variants and human leukocyte antigen (HLA) class II polymorphisms has been suggested in patients with cervical cancer, so far little information is available about the possible interaction between E6 variants and HLA class II variability during the obviously accelerated progression to cervical cancer in young women. In this study, we aimed to explore the association between the HPV16 E6 variants and HLA-DRB1, DQB1 alleles in a Chinese young cervical cancer population. The HLA-DRB1, HLA-DQB1 polymophisms were genotyped by low-resolution polymerase chain reaction (PCR) with sequence-specific primer. HPV16 E6 DNA was tested by Sanger fluorescent dye dideoxy-termination technique. The difference of DRB1, DQB1 polymorphisms between young cervical cancer patients (≤35ys, n=61) and older ones (>35ys, n=85) and the association with E6 variants were analyzed. Results showed that the distribution pattern of HLA-DRB1, DQB1 alleles was different between young cervical cancer patients and older ones. The allele frequency of DQB1*0501 in young patients was significantly lower than older ones (6.6% vs. 23.5%, p<0.05). The HPV16 E6 A4 lineage was the exclusive type observed in young patients, and its prevalence was significantly higher than that of older cases (82.86% vs.41.94%, p<0.05). DRB1*03 was not found in young patients positive for the HPV16 E6 A4 lineage, whereas it was observed in 19.2 % older patients with A4 positive(Pc<0.05). In conclusion, specific association between certain HPV16 E6 variant and genetic polymorphisms of HLA may play a role during the progression of early onset cervical cancer in young patients. Certain HLA-DRB1 and HLA-DQB1 alleles may be related to the A4 lineage among young cervical cancer patients, which was the unique HPV16 E6 variant found in Chinese young patients. Our finding may provide an insight into the pathogenic factors that associated with cervical cancer in young women.

Dataset Information

HLA Polymorphisms And TKI-Induced Liver Injury in Patients with Cancer: A Meta-analysis.

Publications

HLA Polymorphisms And TKI-Induced Liver Injury in Patients with Cancer: A Meta-analysis.

Similar Datasets

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