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.
Cancer Institute, Cancer Center, Sun Yat-sen University, GuangZhou, China.
Bing-Jian
BJ
Feng
Wei
W
Huang
Yin Yao
YY
Shugart
Ming K
MK
Lee
Feng
F
Zhang
Jian-Chuan
JC
Xia
Hui-Yun
HY
Wang
Teng-Bo
TB
Huang
Shao-Wen
SW
Jian
Ping
P
Huang
Qi-Sheng
QS
Feng
Li-Xi
LX
Huang
Xing-Juan
XJ
Yu
Duang
D
Li
Li-Zheng
LZ
Chen
Wei-Hua
WH
Jia
Yan
Y
Fang
Hui-Ming
HM
Huang
Jing-Liu
JL
Zhu
Xiao-Ming
XM
Liu
Yan
Y
Zhao
Wang-Qing
WQ
Liu
Mang-Quan
MQ
Deng
Wei-Han
WH
Hu
Shao-Xiong
SX
Wu
Hao-Yuan
HY
Mo
Ming-Fang
MF
Hong
Mary Claire
MC
King
Zhu
Z
Chen
Yi-Xin
YX
Zeng
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