Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4.
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 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.
Feng
Bing-Jian
BJ
Cancer Institute, Cancer Center, Sun Yat-sen University, GuangZhou, China.
Huang
Wei
W
Shugart
Yin Yao
YY
Lee
Ming K
MK
Zhang
Feng
F
Xia
Jian-Chuan
JC
Wang
Hui-Yun
HY
Huang
Teng-Bo
TB
Jian
Shao-Wen
SW
Huang
Ping
P
Feng
Qi-Sheng
QS
Huang
Li-Xi
LX
Yu
Xing-Juan
XJ
Li
Duang
D
Chen
Li-Zheng
LZ
Jia
Wei-Hua
WH
Fang
Yan
Y
Huang
Hui-Ming
HM
Zhu
Jing-Liu
JL
Liu
Xiao-Ming
XM
Zhao
Yan
Y
Liu
Wang-Qing
WQ
Deng
Mang-Quan
MQ
Hu
Wei-Han
WH
Wu
Shao-Xiong
SX
Mo
Hao-Yuan
HY
Hong
Ming-Fang
MF
King
Mary Claire
MC
Chen
Zhu
Z
Zeng
Yi-Xin
YX
D000328:Adult; D044466:Asian People / Q000235:genetics; D002277:Carcinoma / Q000235:genetics* / Q000821:virology; D002681:China; D002881:Chromosomes, Human, Pair 12; D002894:Chromosomes, Human, Pair 4; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D004854:Herpesvirus 4, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000821:virology; D010375:Pedigree; D011995:Recombination, Genetic
D005819:Genetic Markers