The Evolving Epidemiology of Nasopharyngeal Carcinoma

Abstract

Background: The epidemiology of nasopharyngeal carcinoma (NPC) has long been a source of fascination due to the malignancy's striking geographic distribution, the involvement of the oncogenic Epstein-Barr virus (EBV), the unique association with intake of Chinese-style salt-preserved fish, and etiologic heterogeneity by histologic subtype.Methods: This review summarizes the current epidemiologic literature on NPC, highlighting recent results from our populationbased case-control study in southern China.Results: Findings from our case-control study provide new insight into the epidemiology of NPC, including a diminished role of Chinese-style salt-preserved fish, a profound impact of EBV genetic sequence variation, modest positive associations with passive smoking and household air pollution, and possible effects of oral health and the oral microbiome. Recent findings from other studies include a protective association with infectious mononucleosis, suggesting a causal role of early EBV infection; familial risk conferred by shared genetic variation in the host antibody-mediated immune response to EBV infection; and an unclear association with occupational exposure to formaldehyde.Conclusions: To shed further light on the interplay of environmental, genetic, and viral causes of NPC, large pooled studies must accumulate sufficient cases with detailed exposure data.Impact: New epidemiologic findings have reshaped the causal model for NPC.

Associations between ALDH Genetic Variants, Alcohol Consumption, and the Risk of Nasopharyngeal Carcinoma in an East Asian Population

“…We also observed that betel nut chewing was significantly associated with NPC risk. Although three previous studies found no such association [44], a positive association has been reported between betel nut chewing and NPC risk in NPC high-risk families in Taiwan [45]. A modestly increased risk of NPC associated with tobacco smoking has been reported in southern China [46], which is consistent with our study.…”

Epstein–Barr Virus—Associated Malignancies and Immune Escape: The Role of the Tumor Microenvironment and Tumor Cell Evasion Strategies

“…Chronic EBV infection of different tissues of mainly epithelial and lymphocytic origin has been associated with malignant diseases such as carcinomas, lymphomas/lymphoproliferative disorders and soft-tissue tumors [17][18][19][20][21]. Geographically, EBV-associated neoplasia is present worldwide but is more frequent in Asia and Africa compared to the Western world [17,[22][23][24][25] with a higher incidence in males than in females [2,26]. Furthermore, different EBV-associated tumor entities present distinct peaks in the disease onset.…”

“…A comprehensive summary concerning the geographic and epidemiologic peculiarities of EBV-associated malignancies is shown in Table 1. South East Asia, North and East Africa [17,22] gastric adenocarcinoma (GC) 1:100,000 ~9% frequently < 60 years worldwide [18,27,28] intrahepatic cholangiocarcinoma (ICC) <0.01:100,000 6.6% 24-68 years South East Asia [23,29,30] Lymphomas and lymphoproliferative disorders chronic active EBV infection (CAEBV) rare 100% 5-31 Asia [31,32] mucocutaneous ulcer unknown 100% >60 years worldwide [25,33] Europe and North America [34,35] extranodal NK/T cell lymphoma (ENKTL) rare 100% 17-89 years Asia [36,37] classical Hodgkin lymphoma (cHL) 0.5:100,000 in Asia 2.3:100,000 in Europe 50-90% depending on the subtype 20-65 worldwide [19] plasmablastic lymphoma 0.1:100,000 80% 7-65 years worldwide [25,38] post-transplant lymphoproliferative disease (PTLD) <1% in bone marrow transplanted up to 30% in small bowel transplanted patients 60-80% children more often affected worldwide [39] angioimmunoblastic T-cell lymphoma (AITL) 0.05-0.2:100,000 ~70% 20-86 years Europe [40][41][42] primary effusion lymphoma rare 70% young adults worldwide [25] Burkitt lymphoma (BL) sporadic 0.15:100,000 <15% 15-40 years worldwide [43] Burkitt lymphoma (BL) endemic 3-6:100,000 >90% 2-20 years Central Africa East Africa [20] diffuse large B-cell lymphoma (DLBCL) 5-7:100,000 Europe ~4% Asia ~15% 50-91 years Asia [24,25,44] Soft-tissue tumors leiomyosarcoma associated with immune suppression rare 100% children and adolescents worldwide [45] EBV + inflammatory follicular dendritic cell sarcoma rare Unknown 8-77 years * worldwide [21,46] * Data from 9 cases.…”

SSTR2 in Nasopharyngeal Carcinoma: Relationship with Latent EBV Infection and Potential as a Therapeutic Target

“…The temporal trend of the decreasing incidence in NPC observed in the last 20 years in large cities with prevalent Chinese populations, such as Hong Kong and Singapore, may well be linked to reduced consumption of preserved food, especially in young children. These environmental or dietary factors correlate with the finding that second-generation Chinese born in the West have a lower risk of developing NPC compared to first-generation Chinese immigrants in the same countries, although increasing genetic diversity may also play a role [11,12]. It is important to note, however, that the incidence of NPC in China is highly heterogenous with record incidence rates in the south of the country and some of the lowest rates in the world in the northern part.…”

“…A total of 22 microRNAs (miR-BARTs) are encoded in the intronic regions of BamHI fragment A rightward transcripts (BARTs) of the EBV genome. These include: miR-BART2 and two microRNA clusters, cluster 1 (miR-BART1, 3,4,5,6,15,16,17) and cluster 2 (miR-BART7, 8,9,10,11,12,13,14,18,19,20,22) based on their locations on the BamHI-A region [40]. EBV miR-BART microRNAs target and repress cellular pro-apoptotic genes, promoting host cell survival through binding and downregulating cellular mRNAs.…”