PMID- 21272439
OWN - NLM
STAT- MEDLINE
DCOM- 20120824
LR  - 20220502
IS  - 1000-467X (Print)
IS  - 1944-446X (Electronic)
IS  - 1944-446X (Linking)
VI  - 30
IP  - 2
DP  - 2011 Feb
TI  - Nasopharyngeal carcinoma as a paradigm of cancer genetics.
PG  - 79-84
AB  - The unusual incidence patterns for nasopharyngeal carcinoma (NPC) in China, 
      Northeast India, Arctic Inuit, Peninsular and island Southeast Asia, Polynesian 
      Islanders, and North Africans indicate a role for NPC risk genes in Chinese, 
      Chinese-related, and not-obviously Chinese-related populations. Renewed interest 
      in NPC genetic risk has been stimulated by a hypothesis that NPC population 
      patterns originated in Bai-Yue / pre-Austronesian-speaking aborigines and were 
      dispersed during the last glacial maximum by Sundaland submersion. Five articles 
      in this issue of the Chinese Journal of Cancer, first presented at a meeting on 
      genetic aspects of NPC [National Cancer Center of Singapore (NCCS), February 
      20-21, 2010], are directed towards incidence patterns, to early detection of 
      affected individuals within risk populations, and to the application of genetic 
      technology advances to understanding the nature of high risk. Turnbull presents a 
      general framework for understanding population migrations that underlie NPC and 
      similar complex diseases, including other viral cancers. Trejaut et al. apply 
      genetic markers to detail migration from East Asia through Taiwan to the 
      populating of Island Polynesia. Migration dispersal in a westward direction took 
      mongoloid peoples to modern day Northeast India adjacent to Western China 
      (Xinjiang). NPC incidence in mongoloid Nagas ranks amongst the highest in the 
      world, whereas elsewhere in India NPC is uncommon. Cao et al. detail incidence 
      patterns in Southeast China that have occurred over recent decades. Finally, Ji 
      et al. describe the utility of Epstein-Barr virus serostatus in early NPC 
      detection. While genetic risk factors still remain largely unknown, human 
      leukocyte antigen (HLA) genes have been a focus of attention since the discovery 
      of an HLA association with NPC in 1973 and, two years later, that NPC 
      susceptibility in highest-risk Cantonese involved the co-occurrence of multi-HLA 
      locus combinations of HLA genes as chromosome combinations, or haplotypes (e.g. 
      HLA-A2-B46), whereas in relatively lower-risk non-Cantonese Chinese (Hokkiens, 
      Teochews) they appeared to act independently, a strength of association 
      reflecting the 30-50-fold difference in incidence between highest risk Cantonese 
      and lowest-risk Indians. The prototypic haplotype HLA-A2-B46 extends over 
      megabases. An upstream DNA segment (near HLA-DPA1), has close similarity to 
      Gorilla, with no obvious homology to Chimpanzee in current databases, suggesting 
      that a reticulate model of primate evolution may be more appropriate than simple 
      phylogeny. The DNA variation level in this segment is high enough for it to be a 
      hominin remnant. HLA-B46 arose in mongoloids and remains largely limited to 
      Chinese so the question arises as to whether the hominin candidate segment 
      indicates an eastward trek of Homo neanderthalensis or the survival of much 
      earlier Homo erectus? In 2011 sequencing technologies have finally caught up with 
      the requirement to separate parental haplotypes. Recently achieved chromosome 
      separation for whole genome di-haploid genetic and epigenetic analysis of 
      parental inheritance in single individuals will reveal interacting patterns of 
      multi-locus haplotypes as humans move in and through successive environments, 
      thus providing definitive information on the genetic affinities between extant 
      populations, and of the migrations that have led to the global distribution of 
      modern Homo. The challenge can now be met of seeking HLA-associated locations 
      both within and outside the HLA complex on each of the pair of chromosomes. More 
      broadly, for every disease, genetic risk detection will require resolution of the 
      diploid genome as a di-haplome. In the context of NPC, HLA genetic risk complete 
      autosomal di-haplomic sequencing will enable testing of the Wee unitary origin 
      hypothesis of NPC risk even among populations with no apparent mongoloid 
      affinity.
FAU - Simons, Malcolm J
AU  - Simons MJ
AD  - Department of Experimental Research, Sun Yat-sen University Cancer Center, 
      Guangzhou, Guandong 510060, PR China. drsimons@haplomics.com
LA  - eng
PT  - Editorial
PL  - England
TA  - Chin J Cancer
JT  - Chinese journal of cancer
JID - 101498232
SB  - IM
MH  - China/epidemiology
MH  - *Emigration and Immigration
MH  - *Genetics, Population
MH  - Herpesvirus 4, Human/immunology
MH  - Humans
MH  - Nasopharyngeal Neoplasms/ethnology/*genetics/immunology
PMC - PMC4013336
EDAT- 2011/01/29 06:00
MHDA- 2012/08/25 06:00
PMCR- 2011/02/01
CRDT- 2011/01/29 06:00
PHST- 2011/01/29 06:00 [entrez]
PHST- 2011/01/29 06:00 [pubmed]
PHST- 2012/08/25 06:00 [medline]
PHST- 2011/02/01 00:00 [pmc-release]
AID - 1944-446X20110279 [pii]
AID - cjc-30-02-079 [pii]
AID - 10.5732/cjc.010.10609 [doi]
PST - ppublish
SO  - Chin J Cancer. 2011 Feb;30(2):79-84. doi: 10.5732/cjc.010.10609.