Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4
Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4
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DOI：
10.1038/ng932
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发表时间：
2002-08-01
期刊：
影响因子：
30.8
通讯作者：
Zeng, YX
中科院分区：
文献类型：
--
作者：
Feng, BJ;Huang, W;Zeng, YX
鼻咽癌（Nasopharyngeal carcinoma，NPC）在亚洲人群中发病率很高，尤其是广东人。在高发地区，NPC在家庭中聚集，这表明地理和遗传可能会影响疾病风险（1-6）。虽然HLA-Bw 46基因座与NPC的风险增加相关7，8，但迄今为止尚未鉴定出易感基因。在这里，我们报告的结果进行了全基因组搜索在中国广东省的鼻咽癌高危家庭。参数分析提供了与4号染色体上的D4 S405标记连锁的证据，连锁的对数比值（lod）评分为3.06，异质性调整的lod（hlod）评分为3.21。用D4 S405侧翼的额外标记进行精细作图，导致区域4p15.1-q12的lod得分为3.54，hlod得分为3.67。多点非参数连锁分析得出D4 S405的lod评分为3.54（P = 5.4 x 10（-5）），D4 S3002的lod评分为4.2（P = 1.1 x 10（-5）），D4 S3002距离D4 S405 4.5 cM。当EB病毒抗体滴度作为协变量时，D4 S405和D4 S3002的lod评分分别达到4.70（P = 2.0 x 10（-5））和5.36（P = 4.36 x 10（-6））。我们的研究结果提供了一个主要的易感基因座鼻咽癌的4号染色体上的一个子集的家庭的证据。
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(1-6). Although the HLA-Bw46 locus is associated with increased risk of NPC7,8, 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 x 10(-5)) and 4.2 at D4S3002 (P = 1.1 x 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 x 10(-5)) and 5.36 (P = 4.36 x 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.