Nasopharyngeal Carcinoma (NPC)
Genetics and Epstein-Barr virus in the pathogenesis of NPC.
Six case-control studies have shown consistent HLA associations
among our Chinese NPC patients. These findings have been confirmed
in many countries with a sizable Chinese population. Sibpair studies
from China, Hong Kong, Malaysia and Singapore not only confirmed the
linkage with HLA but also indicated that both chromosome sixes are
involved. Our current interests are in using computer program
predictions of EBV peptide binding to at risk and protective HLA
alleles and validate these predictions with the binding of
synthesized peptides to the relevant HLA alleles. The ability of
these HLA peptide combinations to bind to and stimulate relevant T
cells is tested using tetramer technology and Elispot assays. SNPs
are also used to scan chromosome six of patients and controls for
other genes associated with NPC. We have also started to look at the
contribution of NK receptors to the aetiology of NPC.
First degree relatives of NPC patients are at high risk of
developing NPC and many normal relatives have raised EBV serology.
Together with the ENT department NUH, we are monitoring relatives of
NPC patients with HLA, EBV serology and serum EBV DNA copy numbers
for the early detection of NPC.
and vaccine efficacy of infectious diseases in Singapore.
We have monitored
exposure to dengue, EV71, Haemophilus influenzae infections in
Singapoean children and the need for Hepatitis B and acellular
pertussis vaccine boosters in children and adults.
HX, Srinivasan N, Ren EC and Chan SH. Identificationof CD8+ T
cell epitopes specific for immediate-early transactivator Rta of
Epstein-Barr virus. Hu Immunol. 2005; in press.
H, Tang KF, Chua YN, Lu JH, Feng P, Chew TC and Chan SH.
Expression of interleukin-18 by nasopharyngeal carcinoma cells: a
factor that possibly initiates the massive leukocyte infiltration.
Hu Pathol. 2004; 35(6): 722-728.
JY, Chan SH, Yap EH and Hu H. Induction of acute
graft-versus-host disease by T cells that do not respond to in
vitro alloantigen stimulation. Brit J Haematol. 2004; 126:
HX, Ren EC and Chan SH. Associations of HLA microsatellites with
rheumatoid arthritis in Singaporean Chinese. Tissue Antigens.
2003 Aug; 62(2): 133-8.
EE, Phoon MC, Ishak B and Chan SH. Seroepidemiology of human
enterovirus 71, Singapore. Emerg Infect Dis. 2002 Sep; 8(9):
W, Ren EC, Chan SH, Gong WK and Yap HK. Increased HLA- A*11 in
Chinese children with steroid-responsive nephrotic syndrome.
Pediatr Nephrol. 2002 Mar; 17(3): 212-6.
P, Chan SH, Soo MY, Liu D, Guan M, Ren EC and Hu H. Antibody
response to Epstein-Barr virus Rta protein in patients with
nasopharyngeal carcinoma: a new serologic parameter for diagnosis.
Cancer. 2001 Oct 1; 92(7): 1872-80.
P, Ren EC, Liu D, Chan SH and Hu H. Expression of Epstein-Barr
virus lytic gene BRLF1 in nasopharyngeal carcinoma: potential use in
diagnosis. J Gen Virol. 2001 Oct; 81 Pt 10: 2417-23.
EE, Hart TJ, Tan HC and Chan SH. Dengue seroepidemiology in
Singapore. Lancet. 2001 Mar 3; 357(9257): 685-6.
B, New JY, Yap EH, Lu J, Chan SH and Hu H. Blocking L-selectin
and alpha4-integrin changes donor cell homing pattern and
ameliorates murine acute graft versus host disease. Eur J
Immunol. 2001 Feb; 31(2): 617-24.