Identification of genes with allelic imbalance on 6p associated with nasopharyngeal carcinoma in southern Chinese.

Nasopharyngeal carcinoma (NPC) is a malignancy of epithelial origin. The etiology of NPC is complex and includes multiple genetic and environmental factors. We employed case-control analysis to study the association of chromosome 6p regions with NPC. In total, 360 subjects and 360 healthy controls w...

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Autores principales: Yan Li, Li Fu, Alissa Michelle Go Wong, Yan-Hui Fan, Miao-Xin Li, Jin-Xin Bei, Wei-Hua Jia, Yi-Xin Zeng, Danny Chan, Kenneth M C Cheung, Pak Sham, Daniel Chua, Xin-Yuan Guan, You-Qiang Song
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spelling oai:doaj.org-article:9730bf7adc4d4b65aefd51324335f2fc2021-11-18T07:00:09ZIdentification of genes with allelic imbalance on 6p associated with nasopharyngeal carcinoma in southern Chinese.1932-620310.1371/journal.pone.0014562https://doaj.org/article/9730bf7adc4d4b65aefd51324335f2fc2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21283797/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Nasopharyngeal carcinoma (NPC) is a malignancy of epithelial origin. The etiology of NPC is complex and includes multiple genetic and environmental factors. We employed case-control analysis to study the association of chromosome 6p regions with NPC. In total, 360 subjects and 360 healthy controls were included, and 233 single nucleotide polymorphisms (SNPs) on 6p were examined. Significant single-marker associations were found for SNPs rs2267633 (p = 4.49 × 10(-5)), rs2076483 (most significant, p = 3.36 × 10(-5)), and rs29230 (p=1.43 × 10(-4)). The highly associated genes were the gamma-amino butyric acid B receptor 1 (GABBR1), human leukocyte antigen (HLA-A), and HLA complex group 9 (HCG9). Haplotypic associations were found for haplotypes AAA (located within GABBR1, p-value  = 6.46 × 10(-5)) and TT (located within HLA-A, p = 0.0014). Further investigation of the homozygous genotype frequencies between cases and controls suggested that micro-deletion regions occur in GABBR1 and neural precursor cell expressed developmentally down-regulated 9 (NEDD9). Quantitative real-time polymerase chain reaction (qPCR) using 11 pairs of NPC biopsy samples confirmed the significant decline in GABBR1 and NEDD9 mRNA expression in the cancer tissues compared to the adjacent non-tumor tissue (p<0.05). Our study demonstrates that multiple chromosome 6p susceptibility loci contribute to the risk of NPC, possibly though GABBR1 and NEDD9 loss of function.Yan LiLi FuAlissa Michelle Go WongYan-Hui FanMiao-Xin LiJin-Xin BeiWei-Hua JiaYi-Xin ZengDanny ChanKenneth M C CheungPak ShamDaniel ChuaXin-Yuan GuanXin-Yuan GuanYou-Qiang SongPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 1, p e14562 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yan Li
Li Fu
Alissa Michelle Go Wong
Yan-Hui Fan
Miao-Xin Li
Jin-Xin Bei
Wei-Hua Jia
Yi-Xin Zeng
Danny Chan
Kenneth M C Cheung
Pak Sham
Daniel Chua
Xin-Yuan Guan
Xin-Yuan Guan
You-Qiang Song
Identification of genes with allelic imbalance on 6p associated with nasopharyngeal carcinoma in southern Chinese.
description Nasopharyngeal carcinoma (NPC) is a malignancy of epithelial origin. The etiology of NPC is complex and includes multiple genetic and environmental factors. We employed case-control analysis to study the association of chromosome 6p regions with NPC. In total, 360 subjects and 360 healthy controls were included, and 233 single nucleotide polymorphisms (SNPs) on 6p were examined. Significant single-marker associations were found for SNPs rs2267633 (p = 4.49 × 10(-5)), rs2076483 (most significant, p = 3.36 × 10(-5)), and rs29230 (p=1.43 × 10(-4)). The highly associated genes were the gamma-amino butyric acid B receptor 1 (GABBR1), human leukocyte antigen (HLA-A), and HLA complex group 9 (HCG9). Haplotypic associations were found for haplotypes AAA (located within GABBR1, p-value  = 6.46 × 10(-5)) and TT (located within HLA-A, p = 0.0014). Further investigation of the homozygous genotype frequencies between cases and controls suggested that micro-deletion regions occur in GABBR1 and neural precursor cell expressed developmentally down-regulated 9 (NEDD9). Quantitative real-time polymerase chain reaction (qPCR) using 11 pairs of NPC biopsy samples confirmed the significant decline in GABBR1 and NEDD9 mRNA expression in the cancer tissues compared to the adjacent non-tumor tissue (p<0.05). Our study demonstrates that multiple chromosome 6p susceptibility loci contribute to the risk of NPC, possibly though GABBR1 and NEDD9 loss of function.
format article
author Yan Li
Li Fu
Alissa Michelle Go Wong
Yan-Hui Fan
Miao-Xin Li
Jin-Xin Bei
Wei-Hua Jia
Yi-Xin Zeng
Danny Chan
Kenneth M C Cheung
Pak Sham
Daniel Chua
Xin-Yuan Guan
Xin-Yuan Guan
You-Qiang Song
author_facet Yan Li
Li Fu
Alissa Michelle Go Wong
Yan-Hui Fan
Miao-Xin Li
Jin-Xin Bei
Wei-Hua Jia
Yi-Xin Zeng
Danny Chan
Kenneth M C Cheung
Pak Sham
Daniel Chua
Xin-Yuan Guan
Xin-Yuan Guan
You-Qiang Song
author_sort Yan Li
title Identification of genes with allelic imbalance on 6p associated with nasopharyngeal carcinoma in southern Chinese.
title_short Identification of genes with allelic imbalance on 6p associated with nasopharyngeal carcinoma in southern Chinese.
title_full Identification of genes with allelic imbalance on 6p associated with nasopharyngeal carcinoma in southern Chinese.
title_fullStr Identification of genes with allelic imbalance on 6p associated with nasopharyngeal carcinoma in southern Chinese.
title_full_unstemmed Identification of genes with allelic imbalance on 6p associated with nasopharyngeal carcinoma in southern Chinese.
title_sort identification of genes with allelic imbalance on 6p associated with nasopharyngeal carcinoma in southern chinese.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/9730bf7adc4d4b65aefd51324335f2fc
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