Association of melatonin membrane receptor 1A/1B gene polymorphisms with the occurrence and metastasis of hepatocellular carcinoma

Shih Chi Su, Yung Chuan Ho, Yu Fan Liu, Russel J Reiter, Chia Hsuan Chou, Chia Ming Yeh, Hsiang Lin Lee, Wen Hung Chung, Ming Ju Hsieh, Shun Fa Yang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Hepatocellular carcinoma (HCC) is a prevalent primary neoplasm of the liver, whose heterogeneous global incidence suggests the likely impact of genetic variations among individuals on the susceptibility to this disease. Increasing evidence indicates that melatonin exhibits oncostatic properties in many cancer types at least in part mediated by its membrane-bound receptors, melatonin receptor 1A (encoded by MTNR1A) and 1B (MTNR1B). In this study, the effect of melatonin receptor gene polymorphisms on the risk and progression of hepatic tumors was evaluated between 335 HCC patients and 1196 cancer-free subjects. We detected a significant association of MTNR1A single nucleotide polymorphism (SNP), rs6553010, with the elevated risk of HCC (AOR, 1.587; 95% CI, 1.053-2.389; p = 0.027) after being adjusted for two potential confounders, age and alcohol use. In addition, patients who carry at least one polymorphic allele (heterozygote or homozygote) of MTNR1A rs2119882 or rs2375801 were more prone to develop distant metastasis (OR, 5.202; 95% CI, 1.163-23.270; p = 0.031, and OR, 7.782; 95% CI, 1.015-59.663; p = 0.048, for rs2119882 and rs2375801, respectively). Further analyses revealed that rs2119882 is located on the consensus binding site of GATA2 transcription factor within the promoter region of MTNR1A gene, and that a correlation between the levels of GATA2 and melatonin receptor 1A was observed in the TCGA (The Cancer Genome Atlas) dataset. Moreover, individuals bearing a specific haplotype of four MTNR1B SNPs were more prone to develop HCC. In conclusion, our data suggest an association of melatonin receptor gene polymorphisms with the risk of HCC and hepatic cancer metastasis.

Original languageEnglish (US)
Pages (from-to)85655-85669
Number of pages15
JournalOncotarget
Volume8
Issue number49
DOIs
StatePublished - Oct 17 2017

Fingerprint

Melatonin Receptors
Hepatocellular Carcinoma
Neoplasm Metastasis
Liver Neoplasms
Membranes
Genes
Single Nucleotide Polymorphism
GATA2 Transcription Factor
Neoplasms
Atlases
Disease Susceptibility
Homozygote
Melatonin
Heterozygote
Genetic Promoter Regions
Haplotypes
Alleles
Binding Sites
Alcohols
Genome

Keywords

  • Hepatocellular carcinoma
  • Melatonin receptor
  • Metastasis
  • Polymorphism

ASJC Scopus subject areas

  • Oncology

Cite this

Association of melatonin membrane receptor 1A/1B gene polymorphisms with the occurrence and metastasis of hepatocellular carcinoma. / Su, Shih Chi; Ho, Yung Chuan; Liu, Yu Fan; Reiter, Russel J; Chou, Chia Hsuan; Yeh, Chia Ming; Lee, Hsiang Lin; Chung, Wen Hung; Hsieh, Ming Ju; Yang, Shun Fa.

In: Oncotarget, Vol. 8, No. 49, 17.10.2017, p. 85655-85669.

Research output: Contribution to journalArticle

Su, SC, Ho, YC, Liu, YF, Reiter, RJ, Chou, CH, Yeh, CM, Lee, HL, Chung, WH, Hsieh, MJ & Yang, SF 2017, 'Association of melatonin membrane receptor 1A/1B gene polymorphisms with the occurrence and metastasis of hepatocellular carcinoma', Oncotarget, vol. 8, no. 49, pp. 85655-85669. https://doi.org/10.18632/oncotarget.21107
Su, Shih Chi ; Ho, Yung Chuan ; Liu, Yu Fan ; Reiter, Russel J ; Chou, Chia Hsuan ; Yeh, Chia Ming ; Lee, Hsiang Lin ; Chung, Wen Hung ; Hsieh, Ming Ju ; Yang, Shun Fa. / Association of melatonin membrane receptor 1A/1B gene polymorphisms with the occurrence and metastasis of hepatocellular carcinoma. In: Oncotarget. 2017 ; Vol. 8, No. 49. pp. 85655-85669.
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abstract = "Hepatocellular carcinoma (HCC) is a prevalent primary neoplasm of the liver, whose heterogeneous global incidence suggests the likely impact of genetic variations among individuals on the susceptibility to this disease. Increasing evidence indicates that melatonin exhibits oncostatic properties in many cancer types at least in part mediated by its membrane-bound receptors, melatonin receptor 1A (encoded by MTNR1A) and 1B (MTNR1B). In this study, the effect of melatonin receptor gene polymorphisms on the risk and progression of hepatic tumors was evaluated between 335 HCC patients and 1196 cancer-free subjects. We detected a significant association of MTNR1A single nucleotide polymorphism (SNP), rs6553010, with the elevated risk of HCC (AOR, 1.587; 95{\%} CI, 1.053-2.389; p = 0.027) after being adjusted for two potential confounders, age and alcohol use. In addition, patients who carry at least one polymorphic allele (heterozygote or homozygote) of MTNR1A rs2119882 or rs2375801 were more prone to develop distant metastasis (OR, 5.202; 95{\%} CI, 1.163-23.270; p = 0.031, and OR, 7.782; 95{\%} CI, 1.015-59.663; p = 0.048, for rs2119882 and rs2375801, respectively). Further analyses revealed that rs2119882 is located on the consensus binding site of GATA2 transcription factor within the promoter region of MTNR1A gene, and that a correlation between the levels of GATA2 and melatonin receptor 1A was observed in the TCGA (The Cancer Genome Atlas) dataset. Moreover, individuals bearing a specific haplotype of four MTNR1B SNPs were more prone to develop HCC. In conclusion, our data suggest an association of melatonin receptor gene polymorphisms with the risk of HCC and hepatic cancer metastasis.",
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AU - Chou, Chia Hsuan

AU - Yeh, Chia Ming

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AB - Hepatocellular carcinoma (HCC) is a prevalent primary neoplasm of the liver, whose heterogeneous global incidence suggests the likely impact of genetic variations among individuals on the susceptibility to this disease. Increasing evidence indicates that melatonin exhibits oncostatic properties in many cancer types at least in part mediated by its membrane-bound receptors, melatonin receptor 1A (encoded by MTNR1A) and 1B (MTNR1B). In this study, the effect of melatonin receptor gene polymorphisms on the risk and progression of hepatic tumors was evaluated between 335 HCC patients and 1196 cancer-free subjects. We detected a significant association of MTNR1A single nucleotide polymorphism (SNP), rs6553010, with the elevated risk of HCC (AOR, 1.587; 95% CI, 1.053-2.389; p = 0.027) after being adjusted for two potential confounders, age and alcohol use. In addition, patients who carry at least one polymorphic allele (heterozygote or homozygote) of MTNR1A rs2119882 or rs2375801 were more prone to develop distant metastasis (OR, 5.202; 95% CI, 1.163-23.270; p = 0.031, and OR, 7.782; 95% CI, 1.015-59.663; p = 0.048, for rs2119882 and rs2375801, respectively). Further analyses revealed that rs2119882 is located on the consensus binding site of GATA2 transcription factor within the promoter region of MTNR1A gene, and that a correlation between the levels of GATA2 and melatonin receptor 1A was observed in the TCGA (The Cancer Genome Atlas) dataset. Moreover, individuals bearing a specific haplotype of four MTNR1B SNPs were more prone to develop HCC. In conclusion, our data suggest an association of melatonin receptor gene polymorphisms with the risk of HCC and hepatic cancer metastasis.

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