Insertion-Deletion Polymorphisms in the Promoter Region of BRM Contribute to Risk of Hepatocellular Carcinoma in Chinese PopulationsReport as inadecuate




Insertion-Deletion Polymorphisms in the Promoter Region of BRM Contribute to Risk of Hepatocellular Carcinoma in Chinese Populations - Download this document for free, or read online. Document in PDF available to download.

Background

BRM Brahma homologue is well known for its critical role in tumor suppression and cancer development. Genetic variations in the promoter region of BRM have been suggested to be associated with loss of BRM expression and lung cancer risk. To the authors’ knowledge, no study on the role of BRM genetic polymorphisms in hepatocellular carcinoma HCC risk has been performed.

Methodology-Principal Findings

In two independent case-control studies containing 796 HCC cases and 806 cancer-free individuals, we genotyped two putative functional insertion-deletion indel polymorphisms BRM-1321 rs3832613 and BRM-741 rs34480940 within promoter region of BRM in Chinese populations using a PCR-based method. Real-time RT-PCR analysis was used to explore the genotype-phenotype correlation between these polymorphisms and BRM expression in both tissue samples and HCC cell lines. Logistic regression analysis showed that compared to BRM-1321del-del genotype, the ins-del and ins-ins variant genotypes had an increased HCC risk adjusted odds ratio OR = 1.47, 95% confidence interval CI = 1.19–1.82; adjusted OR = 2.55, 95% CI = 1.75–3.72, respectively. No significant association between BRM-741 and HCC incidence was observed. However, stratification analysis revealed a significant association between ins-ins genotype of BRM-741 and increased HCC susceptibility in smokers adjusted OR = 2.07, 95% CI = 1.33–3.22. Quantitative PCR analyses demonstrated that the genotypes of BRM-1321 and the corresponding haplotypes were significantly correlated with BRM expression in vivo. Compared with ins-ins genotype, subjects carrying ins-del and del-del genotype had 2.30 and 4.99 fold higher BRM expression in HCC tissue samples, respectively. Similar trends were observed in western blot analysis at protein level.

Conclusions-Significance

Our findings suggest that BRM promoter polymorphism BRM-1321 could regulate BRM expression and may serve as a potential marker for genetic susceptibility to HCC.



Author: Xueren Gao , Moli Huang , Limin Liu , Yan He, Qiang Yu, Hua Zhao, Chunxiao Zhou, Jinkun Zhang, Zhansheng Zhu, Jiao Wan, Xinghong

Source: http://plos.srce.hr/



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