Dataset Information

No association for Chinese HBV-related hepatocellular carcinoma susceptibility SNP in other East Asian populations.

ABSTRACT: BACKGROUND: A recent genome-wide association study (GWAS) using chronic HBV (hepatitis B virus) carriers with and without hepatocellular carcinoma (HCC) in five independent Chinese populations found that one SNP (rs17401966) in KIF1B was associated with susceptibility to HCC. In the present study, a total of 580 HBV-derived HCC cases and 1351 individuals with chronic hepatitis B (CHB) or asymptomatic carrier (ASC) were used for replication studies in order to evaluate the reported association with HBV-derived HCC in other East Asian populations. RESULTS: We did not detect any associations between rs17401966 and HCC in the Japanese cohorts (replication 1: OR?=?1.09, 95?% CI?=?0.82-1.43; replication 2: OR?=?0.79, 95?% CI?=?0.54-1.15), in the Korean cohort (replication 3: OR?=?0.95, 95?% CI?=?0.66-1.36), or in the Hong Kong Chinese cohort (replication 4: OR?=?1.17, 95?% CI?=?0.79-1.75). Meta-analysis using these cohorts also did not show any associations with P?=?0.97. CONCLUSIONS: None of the replication cohorts showed associations between rs17401966 and HBV-derived HCC. This may be due to differences in the genetic diversity among the Japanese, Korean and Chinese populations. Other reasons could be the high complexity of multivariate interactions between the genomic information and the phenotype that is manifesting. A much wider range of investigations is needed in order to elucidate the differences in HCC susceptibility among these Asian populations.

SUBMITTER: Sawai H

PROVIDER: S-EPMC3407509 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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No association for Chinese HBV-related hepatocellular carcinoma susceptibility SNP in other East Asian populations.

Sawai Hiromi H Nishida Nao N Mbarek Hamdi H Matsuda Koichi K Mawatari Yoriko Y Yamaoka Megumi M Hige Shuhei S Kang Jong-Hon JH Abe Koichi K Mochida Satoshi S Watanabe Masaaki M Kurosaki Masayuki M Asahina Yasuhiro Y Izumi Namiki N Honda Masao M Kaneko Shuichi S Tanaka Eiji E Matsuura Kentaro K Itoh Yoshito Y Mita Eiji E Korenaga Masaaki M Hino Keisuke K Murawaki Yoshikazu Y Hiasa Yoichi Y Ide Tatsuya T Ito Kiyoaki K Sugiyama Masaya M Ahn Sang Hoon SH Han Kwang-Hyub KH Park Jun Yong JY Yuen Man-Fung MF Nakamura Yusuke Y Tanaka Yasuhito Y Mizokami Masashi M Tokunaga Katsushi K

BMC medical genetics 20120619

<h4>Background</h4>A recent genome-wide association study (GWAS) using chronic HBV (hepatitis B virus) carriers with and without hepatocellular carcinoma (HCC) in five independent Chinese populations found that one SNP (rs17401966) in KIF1B was associated with susceptibility to HCC. In the present study, a total of 580 HBV-derived HCC cases and 1351 individuals with chronic hepatitis B (CHB) or asymptomatic carrier (ASC) were used for replication studies in order to evaluate the reported associa ...[more]

PMID: 22712471

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Project description:BACKGROUND: PTPN11, which encodes tyrosine phosphatase Shp2, is a critical gene mediating cellular responses to hormones and cytokines. Loss of Shp2 promotes hepatocellular carcinoma (HCC), suggesting that PTPN11 functions as a tumor suppressor in HCC tumorgenesis. The aim of this study was to evaluate the effects of the short tandem repeat (STR) polymorphism (rs199618935) within 3'UTR of PTPN11 on HCC susceptibility in Chinese populations. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the associations in 400 patients from Jiangsu province of China, validating the findings in an additional 305 patients from Shanghai of China. Unconditional logistic regression was used to analyze the association between rs199618935 and HCC risk. Additional biochemical investigations and in-silico studies were used to evaluate the possible functional significance of this polymorphism. Logistic regression analysis showed that compared with individuals carrying shorter alleles (11 and 12 repeats), those subjects who carry longer alleles (13 and 14 repeats) had a significantly decreased risk of HCC [adjusted odds ratio (OR) = 0.63, 95% confidence interval (CI) ?= 0.53-0.76, P = 2.00 × 10(-7)], with the risk decreased even further in those carrying allele 15 and 16 (adjusted OR = 0.46, 95% CI = 0.34-0.62, P = 1.00 × 10(-7)). Biochemical investigations showed that longer alleles of rs199618935 conferred higher PTPN11 expression in vivo and in vitro. The altered luciferase activities in reporter gene system suggested that STR regulation of PTPN11 expression could be a transcriptional event. Finally, in-silico prediction revealed that different alleles of rs199618935 could alter the local structure of PTPN11 mRNA. CONCLUSIONS/SIGNIFICANCE: Taken together, our findings suggested that the STR polymorphism within PTPN11 contributes to hepatocarcinogenesis, possibly by affecting PTPN11 expression through a structure-dependent mechanism. The replication of our studies and further functional studies are needed to validate our findings.

Dataset Information

No association for Chinese HBV-related hepatocellular carcinoma susceptibility SNP in other East Asian populations.

Publications

No association for Chinese HBV-related hepatocellular carcinoma susceptibility SNP in other East Asian populations.

Similar Datasets

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