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LAPTM4B polymorphism increases susceptibility to multiple cancers in Chinese populations: a meta-analysis.

ABSTRACT: BACKGROUND: Lysosome-associated protein transmembrane-4 beta (LAPTM4B) is a novel cancer-related gene. While recent studies have reported that the LAPTM4B polymorphism increased the susceptibility of several cancers, the results remain inconclusive. Therefore, we performed a meta-analysis to systematically summarize the possible association. RESULTS: The meta-analysis was conducted based on 17 studies in Chinese populations, including 4160 cases and 4148 controls. The relevant studies were searched through electronic databases updated in November 2013. The strength of association between the LAPTM4B polymorphism and susceptibility to multiple cancers was assessed by odds ratio (OR) and 95% confidence interval (95% CI).The meta-analysis results suggested that the LAPTM4B polymorphism was significantly associated with overall susceptibility to multiple cancers in all genetic models (*2 vs. *1, OR = 1.53, 95% CI = 1.37-1.70; *2/2 vs. *1/1, OR = 2.18, 95% CI = 1.72-2.75; *2/1 vs.*1/1, OR = 1.62, 95% CI = 1.41-1.86; *2/1 + *2/2 vs. *1/1, OR = 1.70, 95% CI = 1.47-1.97; *2/2 vs. *2/1 + *1/1, OR = 1.76, 95% CI = 1.50-2.05). Further subgroup analysis revealed a significant association between the LAPTM4B polymorphism and cancer susceptibility in the subgroups stratified by control source, cancer type, histopathologic differentiation, and TNM stage. CONCLUSIONS: This meta-analysis indicated that the LAPTM4B *2 allele was associated with increasing risk of multiple cancers, tumor initiation and development.

SUBMITTER: Mo C

PROVIDER: S-EPMC4022328 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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LAPTM4B polymorphism increases susceptibility to multiple cancers in Chinese populations: a meta-analysis.

Mo Cuiju C Lu Yu Y Deng Yan Y Wang Jian J Xie Li L Li Taijie T He Yu Y Peng Qiliu Q Qin Xue X Li Shan S

BMC genetics 20140418

<h4>Background</h4>Lysosome-associated protein transmembrane-4 beta (LAPTM4B) is a novel cancer-related gene. While recent studies have reported that the LAPTM4B polymorphism increased the susceptibility of several cancers, the results remain inconclusive. Therefore, we performed a meta-analysis to systematically summarize the possible association.<h4>Results</h4>The meta-analysis was conducted based on 17 studies in Chinese populations, including 4160 cases and 4148 controls. The relevant studi ...[more]

PMID: 24746178

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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

LAPTM4B polymorphism increases susceptibility to multiple cancers in Chinese populations: a meta-analysis.

Publications

LAPTM4B polymorphism increases susceptibility to multiple cancers in Chinese populations: a meta-analysis.

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