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LIN28A polymorphisms and hepatoblastoma susceptibility in Chinese children.

ABSTRACT: Hepatoblastoma (HB) is the most prevalent primary hepatic cancer in children aged 6 months to 3 years. LIN28A is recurrently mutated in various diseases, and critically involved in tumorigenesis. However, a limited number of studies have examined the involvement of LIN28A polymorphisms in HB risk. We used the TaqMan assay to genotype four LIN28A polymorphisms (rs3811464 G>A, rs3811463 T>C, rs34787247 G>A, and rs11247957 G>A) in 275 Chinese children with HB and 1018 cancer-free controls from five medical centers in China. Their association with HB risk was evaluated on the basis of odds ratio (OR) and corresponding 95% confidence interval (CI). Overall, no significant associations were found in single locus and combine analysis. Interestingly, in the stratified analysis, we found that subjects with 1-3 risk genotypes were more likely to develop HB in patients ?17 months of age (adjusted OR=1.76, 95% CI=1.04-2.98, P=0.034). The rs3811464 GA/AA genotypes were associated with decrease HB risk in patients with clinical stage III+IV disease (adjusted OR=0.50, 95% CI=0.26-0.96, P=0.038). Our results suggest that the LIN28A polymorphisms have a weak association with HB susceptibility in the Chinese children. LIN28A rs3811464 G>A may decrease HB risk in stage III+IV patients which need further validations with larger samples and different ethnicities.

SUBMITTER: Yang Z

PROVIDER: S-EPMC7847658 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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LIN28A polymorphisms and hepatoblastoma susceptibility in Chinese children.

Yang Zhonghua Z Deng Yuyao Y Zhang Keren K Bai Yuzuo Y Zhu Jinhong J Zhang Jiao J Cheng Jiwen J Li Li L He Jing J Wang Weilin W

Journal of Cancer 20210101 5

Hepatoblastoma (HB) is the most prevalent primary hepatic cancer in children aged 6 months to 3 years. LIN28A is recurrently mutated in various diseases, and critically involved in tumorigenesis. However, a limited number of studies have examined the involvement of LIN28A polymorphisms in HB risk. We used the TaqMan assay to genotype four LIN28A polymorphisms (rs3811464 G>A, rs3811463 T>C, rs34787247 G>A, and rs11247957 G>A) in 275 Chinese children with HB and 1018 cancer-fr ...[more]

PMID: 33531982

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Project description:Hepatoblastoma is one of the malignant liver tumors in children. However, genetic mechanisms underpinning the initiation of hepatoblastoma remain largely unclear. The previous study showed that lin-28 homolog B (LIN28B) might play a role in the development of hepatoblastoma. To detect the association between LIN28B gene polymorphisms and hepatoblastoma risk in Chinese children, we conducted a five-center case-control study of 275 hepatoblastoma patients and 1018 cancer-free controls. Four potentially functional polymorphisms were genotyped using the Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the associations. We found that the rs314276 C>A polymorphism (AA vs. CC: adjusted OR=2.05, 95% CI=1.36-3.10, P=0.0006; AA vs. CA/CC: adjusted OR=2.11, 95% CI=1.43-3.12, P=0.0002) and rs9404590 T>G (GG vs. TT: adjusted OR=1.89, 95% CI=1.20-3.00, P=0.007; GG vs. TT/TG: adjusted OR=1.87, 95% CI=1.20-2.92, P=0.006) were associated with increased hepatoblastoma risk. Combination analysis of risk genotypes showed that patients with four risk genotypes had a higher chance of developing hepatoblastoma than carriers of 1 to 3 risk genotypes. Stratification analysis showed the significant association between the rs314276 AA genotype and hepatoblastoma risk in both age and sex groups, as well as clinical stages III+IV cases. The rs9404590 GG genotype was associated with hepatoblastoma risk in participants' ≥17 months, in females, and for those with clinical stages III+IV disease. Furthermore, four risk genotypes confer higher hepatoblastoma susceptibility in both age and sex groups, as well as groups with clinical stages III+IV disease. Genotype-based gene expression analysis confirmed that the rs9404590 T>G polymorphism was significantly associated with altered LIN28B gene expression. We further validated our findings using false-positive probability analysis. This finding suggested that LIN28B gene polymorphisms may be associated with an increased predisposition to hepatoblastoma.

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LIN28A polymorphisms and hepatoblastoma susceptibility in Chinese children.

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<i>LIN28A</i> polymorphisms and hepatoblastoma susceptibility in Chinese children.

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