Genetic predisposition factors and nasopharyngeal carcinoma risk: A review of epidemiological association studies, 2000–2011

Abstract

While infection with Epstein-Barr virus (EBV) is known to be an essential risk factor for the development of nasopharyngeal carcinoma (NPC), other co-factors including genetic factors are thought to play an important role. In this review, we summarize association studies conducted over the past decade to evaluate the role of genetic polymorphisms in NPC development. A review of the literature identified close to 100 studies, including 3 genome-wide association studies (GWAS), since 2000 that evaluated genetic polymorphisms and NPC risk in at least 100 NPC cases and 100 controls. Consistent evidence for associations were reported for a handful of genes, including immune-related HLA Class I genes, DNA repair gene RAD51L1, cell cycle control genes MDM2 and TP53, and cell adhesion/migration gene MMP2. However, for most of the genes evaluated, there was no effort to replicate findings and studies were largely modest in size, typically consisting of no more than a few hundred cases and controls. The small size of most studies, and the lack of attempts at replication have limited progress in understanding the genetics of NPC. Moving forward, if we are to advance our understanding of genetic factors involved in the development of NPC, and of the impact of gene-gene and gene-environment interations in the development of this disease, consortial efforts that pool across multiple, well-designed and coordinated efforts will most likely be required.

Module function and two-way clustering analysis of Epstein-Barr virus-related nasopharyngeal cancer

“…Multiple chromosomal abnormalities (e.g., copy number changes on chromosomes 3p, 9p, 11q, 12p, and 14q), gene alterations (e.g., p16 deletion and LTBR amplification), and epigenetic changes (e.g., RASSF1A and TSLC1 methylation) have been identified using various genome-wide approaches (Lo et al, 2012). Consistent associations with EBV-related NPC have been reported for a handful of genes, including immune-related HLA class I genes, DNA repair gene RAD51L1, cell cycle control genes MDM2 and TP53, and cell adhesion/migration gene MMP2 (Hildesheim and Wang, 2012). New biomarkers for NPC, including EBV DNA copy number or methylation of multiple tumor suppressor genes, which can be detected in serum and nasopharyngeal brushings, have been developed for molecular diagnosis of this tumor (Tao and Chan, 2007).…”

NKG2C copy number variations in five distinct populations in mainland China and susceptibility to nasopharyngeal carcinoma (NPC)

“…Several factors have been implicated in the etiology of NPC, including genetic determinants (most notably the HLA gene complex encoding the human leukocyte antigen), environmental exposures and Epstein-Barr virus (EBV) infection [12]. HLA-E, the only known ligand for NKG2A and NKG2C receptors, has HLA-E ⁄ 01:01 and HLA-E ⁄ 01:03 alleles in the general population [13,14].…”

Association of the p53 or GSTM1 polymorphism with the risk of nasopharyngeal carcinoma: A meta-analysis

“…The incidence is high in South China and East Asia; however, it is rare in the Western world (1)(2)(3)(4). According to epidemiological studies, Epstein-Barr virus (EBV) infection and the environment are two risk factors for the pathogenesis of NPC (5,6). Certain previous studies show that the morbidity of NPC remains high among Chinese individuals who have migrated to North America, which indicates that host genetic factors, including the genetic alterations of tumor suppressor genes and oncogenes, have an important role in the pathogenesis of NPC (7,8).…”