Environmental and Genetic Determinants of NPC
Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in southern China
and Southeast Asia. While infection with Epstein-Barr Virus (EBV) is believed to be
necessary for the development of NPC, non-viral environmental factors have also been
implicated in the carcinogenesis of NPC including consumption of salted fish and other
nitrosamine containing preserved foods, formaldehyde and wood dust exposure, cigarette
smoking, and betel nut chewing. In addition to environmental factors, it is widely accepted
that genetic susceptibility plays an important role in the pathogenesis of NPC.
Polymorphisms in genes involved in antigen presentation, nitrosamine metabolism and DNA
repair have been suggested to be associated with NPC risk, and various chromosomal regions
linked to NPC development have been reported. Two recently completed NPC GWAS have reported
that the strongest evidence for disease association is observed for SNPs located on the 3.6
Mb Major Histocompatibility Complex (MHC) region on chromosome 6p21 where human leukocyte
antigen (HLA) genes are located. These associations highlight the role of both environmental
exposures and genomic variation in the etiology of NPC. However, the specific role of EBV
on NPC pathogenesis is not completely understood and studies to date have had difficulty
pinpointing the specific genetic factors involved in NPC pathogenesis due to the complexity
of the MHC region and limited sample size of candidate gene studies.
DCEG investigators and their Taiwan colleagues have a longstanding history of studies to
elucidate the role of environmental and genetic factors associated with NPC. A case-control
study (375 cases; 327 controls) was conducted in the early 1990s and was followed by a large
multiplex family study that was completed in 2006 (358 families; 3,216 individuals).
Results from these studies have provided a substantial portion of the epidemiological
evidence regarding factors linked to NPC development to date.
At this time, we propose a new case-control study in Taiwan designed to 1) comprehensively
evaluate environmental risk factors for NPC; 2) systematically evaluate genetic risk factors
for NPC for which previous GWAS and candidate-gene studies have suggested an association;
and 3) explore gene-gene and gene-environment interactions for strong main effects
identified in our study. In total, up to 2000 cases and 2000 controls are expected to be
recruited from five participating hospitals in Northern Taiwan. Cases will consist of 550
incident cases ascertained retrospectively and 1350 incident cases ascertained
prospectively. Controls will be hospital based; they will be frequency matched (1:1) to
cases on age, gender and ethnicity, and will exclude individuals referred to the
participating hospitals due to conditions associated with known NPC risk factors.
This project is a collaborative effort between investigators in Taiwan and at the NCI.
Investigators in Taiwan will fund the field recruitment and data collection effort. Results
from this study have the potential to further clarify currently controversial environmental
risk factors as well as elucidate genetic factors of NPC.
Allan Hildesheim, Ph.D.
National Cancer Institute (NCI)
United States: Federal Government