Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4

Bing Jian Feng; Wei Huang; Yin Yao Shugart; Ming K. Lee; Feng Zhang; Jian Chuan Xia; Hui Yun Wang; Teng Bo Huang; Shao Wen Jian; Ping Huang; Qi Sheng Feng; Li Xi Huang; Xing Juan Yu; Duang Li; Li Zheng Chen; Wei Hua Jia; Yan Fang; Hui Ming Huang; Jing Liu Zhu; Xiao Ming Liu; Yan Zhao; Wang Qing Liu; Mang Quan Deng; Wei Han Hu; Shao Xiong Wu; Hao Yuan Mo; Ming Fang Hong; Mary Claire King; Zhu Chen; Yi Xin Zeng

doi:10.1038/ng932

Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4

Bing Jian Feng, Wei Huang, Yin Yao Shugart, Ming K. Lee, Feng Zhang, Jian Chuan Xia, Hui Yun Wang, Teng Bo Huang, Shao Wen Jian, Ping Huang, Qi Sheng Feng, Li Xi Huang, Xing Juan Yu, Duang Li, Li Zheng Chen, Wei Hua Jia, Yan Fang, Hui Ming Huang, Jing Liu Zhu, Xiao Ming LiuYan Zhao, Wang Qing Liu, Mang Quan Deng, Wei Han Hu, Shao Xiong Wu, Hao Yuan Mo, Ming Fang Hong, Mary Claire King, Zhu Chen, Yi Xin Zeng

School of Medicine

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206 Scopus citations

Abstract

Nasopharyngeal carcinoma (NPC) occurs with high frequency in Asian populations, especially among people of Cantonese ancestry. In areas with high incidence, NPC clusters in families, which suggests that both geography and genetics may influence disease risk. Although the HLA-Bw46 locus is associated with increased risk of NPC, no predisposing genes have been identified so far. Here we report the results of a genome-wide search carried out in families at high risk of NPC from Guangdong Province, China. Parametric analyses provide evidence of linkage to the D4S405 marker on chromosome 4 with a logarithm of odds for linkage (lod) score of 3.06 and a heterogeneity-adjusted lod (hlod) score of 3.21. Fine mapping with additional markers flanking D4S405 resulted in a lod score of 3.54 and hlod score of 3.67 for the region 4p15.1-q12. Multipoint nonparametric linkage analysis gives lod scores of 3.54 at D4S405 (P = 5.4 × 10^-5) and 4.2 at D4S3002 (P = 1.1 × 10^-5), which is positioned 4.5 cM away from D4S405. When Epstein-Barr virus antibody titer was included as a covariate, the lod scores reached 4.70 (P = 2.0 × 10^-s) and 5.36 (P = 4.36 × 10^-6) for D4S405 and D4S3002, respectively. Our findings provide evidence of a major susceptibility locus for NPC on chromosome 4 in a subset of families.

Original language	English (US)
Pages (from-to)	395-399
Number of pages	5
Journal	Nature Genetics
Volume	31
Issue number	4
DOIs	https://doi.org/10.1038/ng932
State	Published - Aug 1 2002

ASJC Scopus subject areas

Genetics(clinical)
Genetics

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10.1038/ng932

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Feng, B. J., Huang, W., Shugart, Y. Y., Lee, M. K., Zhang, F., Xia, J. C., Wang, H. Y., Huang, T. B., Jian, S. W., Huang, P., Feng, Q. S., Huang, L. X., Yu, X. J., Li, D., Chen, L. Z., Jia, W. H., Fang, Y., Huang, H. M., Zhu, J. L., ... Zeng, Y. X. (2002). Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4. Nature Genetics, 31(4), 395-399. https://doi.org/10.1038/ng932

Feng, BJ, Huang, W, Shugart, YY, Lee, MK, Zhang, F, Xia, JC, Wang, HY, Huang, TB, Jian, SW, Huang, P, Feng, QS, Huang, LX, Yu, XJ, Li, D, Chen, LZ, Jia, WH, Fang, Y, Huang, HM, Zhu, JL, Liu, XM, Zhao, Y, Liu, WQ, Deng, MQ, Hu, WH, Wu, SX, Mo, HY, Hong, MF, King, MC, Chen, Z & Zeng, YX 2002, 'Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4', Nature Genetics, vol. 31, no. 4, pp. 395-399. https://doi.org/10.1038/ng932

@article{794d289a19464488a36015f41fa3ef04,

title = "Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4",

abstract = "Nasopharyngeal carcinoma (NPC) occurs with high frequency in Asian populations, especially among people of Cantonese ancestry. In areas with high incidence, NPC clusters in families, which suggests that both geography and genetics may influence disease risk. Although the HLA-Bw46 locus is associated with increased risk of NPC, no predisposing genes have been identified so far. Here we report the results of a genome-wide search carried out in families at high risk of NPC from Guangdong Province, China. Parametric analyses provide evidence of linkage to the D4S405 marker on chromosome 4 with a logarithm of odds for linkage (lod) score of 3.06 and a heterogeneity-adjusted lod (hlod) score of 3.21. Fine mapping with additional markers flanking D4S405 resulted in a lod score of 3.54 and hlod score of 3.67 for the region 4p15.1-q12. Multipoint nonparametric linkage analysis gives lod scores of 3.54 at D4S405 (P = 5.4 × 10-5) and 4.2 at D4S3002 (P = 1.1 × 10-5), which is positioned 4.5 cM away from D4S405. When Epstein-Barr virus antibody titer was included as a covariate, the lod scores reached 4.70 (P = 2.0 × 10-s) and 5.36 (P = 4.36 × 10-6) for D4S405 and D4S3002, respectively. Our findings provide evidence of a major susceptibility locus for NPC on chromosome 4 in a subset of families.",

author = "Feng, {Bing Jian} and Wei Huang and Shugart, {Yin Yao} and Lee, {Ming K.} and Feng Zhang and Xia, {Jian Chuan} and Wang, {Hui Yun} and Huang, {Teng Bo} and Jian, {Shao Wen} and Ping Huang and Feng, {Qi Sheng} and Huang, {Li Xi} and Yu, {Xing Juan} and Duang Li and Chen, {Li Zheng} and Jia, {Wei Hua} and Yan Fang and Huang, {Hui Ming} and Zhu, {Jing Liu} and Liu, {Xiao Ming} and Yan Zhao and Liu, {Wang Qing} and Deng, {Mang Quan} and Hu, {Wei Han} and Wu, {Shao Xiong} and Mo, {Hao Yuan} and Hong, {Ming Fang} and King, {Mary Claire} and Zhu Chen and Zeng, {Yi Xin}",

year = "2002",

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doi = "10.1038/ng932",

language = "English (US)",

volume = "31",

pages = "395--399",

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T1 - Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4

AU - Feng, Bing Jian

AU - Huang, Wei

AU - Shugart, Yin Yao

AU - Lee, Ming K.

AU - Zhang, Feng

AU - Xia, Jian Chuan

AU - Wang, Hui Yun

AU - Huang, Teng Bo

AU - Jian, Shao Wen

AU - Huang, Ping

AU - Feng, Qi Sheng

AU - Huang, Li Xi

AU - Yu, Xing Juan

AU - Li, Duang

AU - Chen, Li Zheng

AU - Jia, Wei Hua

AU - Fang, Yan

AU - Huang, Hui Ming

AU - Zhu, Jing Liu

AU - Liu, Xiao Ming

AU - Zhao, Yan

AU - Liu, Wang Qing

AU - Deng, Mang Quan

AU - Hu, Wei Han

AU - Wu, Shao Xiong

AU - Mo, Hao Yuan

AU - Hong, Ming Fang

AU - King, Mary Claire

AU - Chen, Zhu

AU - Zeng, Yi Xin

PY - 2002/8/1

Y1 - 2002/8/1

N2 - Nasopharyngeal carcinoma (NPC) occurs with high frequency in Asian populations, especially among people of Cantonese ancestry. In areas with high incidence, NPC clusters in families, which suggests that both geography and genetics may influence disease risk. Although the HLA-Bw46 locus is associated with increased risk of NPC, no predisposing genes have been identified so far. Here we report the results of a genome-wide search carried out in families at high risk of NPC from Guangdong Province, China. Parametric analyses provide evidence of linkage to the D4S405 marker on chromosome 4 with a logarithm of odds for linkage (lod) score of 3.06 and a heterogeneity-adjusted lod (hlod) score of 3.21. Fine mapping with additional markers flanking D4S405 resulted in a lod score of 3.54 and hlod score of 3.67 for the region 4p15.1-q12. Multipoint nonparametric linkage analysis gives lod scores of 3.54 at D4S405 (P = 5.4 × 10-5) and 4.2 at D4S3002 (P = 1.1 × 10-5), which is positioned 4.5 cM away from D4S405. When Epstein-Barr virus antibody titer was included as a covariate, the lod scores reached 4.70 (P = 2.0 × 10-s) and 5.36 (P = 4.36 × 10-6) for D4S405 and D4S3002, respectively. Our findings provide evidence of a major susceptibility locus for NPC on chromosome 4 in a subset of families.

AB - Nasopharyngeal carcinoma (NPC) occurs with high frequency in Asian populations, especially among people of Cantonese ancestry. In areas with high incidence, NPC clusters in families, which suggests that both geography and genetics may influence disease risk. Although the HLA-Bw46 locus is associated with increased risk of NPC, no predisposing genes have been identified so far. Here we report the results of a genome-wide search carried out in families at high risk of NPC from Guangdong Province, China. Parametric analyses provide evidence of linkage to the D4S405 marker on chromosome 4 with a logarithm of odds for linkage (lod) score of 3.06 and a heterogeneity-adjusted lod (hlod) score of 3.21. Fine mapping with additional markers flanking D4S405 resulted in a lod score of 3.54 and hlod score of 3.67 for the region 4p15.1-q12. Multipoint nonparametric linkage analysis gives lod scores of 3.54 at D4S405 (P = 5.4 × 10-5) and 4.2 at D4S3002 (P = 1.1 × 10-5), which is positioned 4.5 cM away from D4S405. When Epstein-Barr virus antibody titer was included as a covariate, the lod scores reached 4.70 (P = 2.0 × 10-s) and 5.36 (P = 4.36 × 10-6) for D4S405 and D4S3002, respectively. Our findings provide evidence of a major susceptibility locus for NPC on chromosome 4 in a subset of families.

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Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4

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