Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA –B, and HLA -C class I genes (PHLA-A-aa-site-62 = 7.4×10−29; P HLA-B-aa-site-116 = 6.5×10−19; P HLA-C-aa-site-156 = 6.8×10−8 respectively). Over 250 NPC-HLA associated variants within HLA were analyzed in concert to resolve separate and largely independent HLA-A, -B, and -C gene influences. Multivariate logistical regression analysis collapsed significant associations in adjacent genes spanning 500 kb (OR2H1, GABBR1, HLA-F, and HCG9) as proxies for peptide binding motifs carried by HLA- A*11:01. A similar analysis resolved an independent association signal driven by HLA-B*13:01, B*38:02, and B*55:02 alleles together. NPC resistance alleles carrying the strongly associated amino acid variants implicate specific class I peptide recognition motifs in HLA-A and -B peptide binding groove as conferring strong genetic influence on the development of NPC in China.

To understand the role of environmental and genetic influences on nasopharyngeal carcinoma (NPC) in populations at high risk of NPC, we have performed a case-control study in Guangxi Province of Southern China in 2004-2005. NPC cases (n=1049) were compared to 785 NPC-free matched controls who were seropositive for IgA antibodies (IgA) to Epstein-Barr virus (EBV) capsid antigen (VCA)—a predictive marker for NPC in Chinese populations. A questionnaire was used to capture exposure and NPC family history data. Risk factors associated with NPC in a multivariant analysis model were the following: 1) a first, second or third degree relative with NPC [Attributable risk (AR)= 6%, Odds ratio (OR) = 3.1, 95%CI = 2.0-4.9, p < 0.001]; 2) consumption of salted fish 3 or more than 3 times per month (AR=3%, OR = 1.9, 95%CI = 1.1-3.5, p = 0.035); 3) exposure to domestic wood cooking fires for more than 10 years (AR=69%, OR = 5.8, 95%CI = 2.5-13.6, p < 0.001); and 4) exposure to occupational solvents for 10 or less years (AR=4%, OR = 2.6, 95%CI = 1.4-4.8, p = 0.002). Consumption of preserved meats or a history of tobacco smoking were not associated with NPC (P>0.05). We also assessed the contribution of EBV/IgA/VCA antibody serostatus to NPC risk—32.2% of NPC can be explained by IgA+ status. However, family history and environmental risk factors cumulatively explained only 2.7% of NPC development in NPC high risk population. These findings should have important public health implications for NPC risk reduction in endemic regions.

Summary A case-control study was conducted on 88 incident cases of histologically confirmed undifferentiated nasopharyngeal carcinoma (NPC) in Zangwu County, China, and 176 age-sex-and neighbourhood-matched controls. The design of this study was defined after an anthropological survey on living habits in regions of high NPC incidence and the evidence of carcinogenic substances in some commonly consumed preserved foods. Subjects were interviewed regarding living conditions and diet in the year preceding the diagnosis of NPC and, with the help of their families, during childhood and weaning. After adjustment for a living conditions score to eliminate a confounding effect, an increased risk associated with consumption of salted fish during weaning and childhood was confirmed, especially for salted fish in rice porridge. The consumption of leafy vegetables was associated with a reduced risk for NPC, and consumption of melon seeds between 2 and 10 years of age with an increased risk. After multivariate analysis and adjustment according to the living conditions score, the consumption of salted fish in rice porridge before age 2 (OR = 3.8, P = 0.005), exposure to domestic woodfire (OR = 5.4, P = 0.01) and consumption of herbal tea (OR = 4.2, P = 0.02) were found to be independently related to the risk of NPC. The excess risk associated with the use of domestic wood fire increased if there were no windows in the house and with poor ventilation and cooking outside the house in a shack. As well as confirming the importance of the consumption of salted fish in childhood, this study has been the first to provide unequivocal evidence for two other factors implicated in increasing the risk of NPC in China, the adult consumption of traditional medicines (herbal tea) and exposure to domestic wood fumes.

The peripheral blood neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR) have been reported to correlate with the prognosis of many malignancies. This study evaluated the prognostic value of pretreatment NLR, LMR, and PLR in nasopharyngeal carcinoma (NPC). A retrospective analysis of clinical and pathological data of 140 NPC patients without distant metastasis during initial treatment was conducted to identify correlations between NLR, LMR, and PLR and clinicopathological features, overall survival, and progression-free survival. Cox proportional hazard regression analysis was used to reveal the independent factors affecting the prognosis of NPC patients. NLR was associated with T staging, N staging, and overall clinical stage grouping of the NPC patients (P < 0.05). NLR ≥ 2.28, LMR < 2.26, and PLR ≥ 174 were significantly associated with a relatively short overall survival (P < 0.05). In addition, NLR ≥ 2.28 was significantly associated with a relatively short progression-free survival (P < 0.05). Cox proportional hazard regression analysis showed that NLR was an independent prognostic factor in NPC. Pretreatment NLR, LMR, and PLR might be a useful complement to TNM staging in the prognostic assessment of NPC patients.

The magnitude and patterns of associations between smoking and risk of nasopharyngeal carcinoma (NPC) in high-incidence regions remain uncertain. Associations with active and passive tobacco smoking were estimated using multivariate logistic regression in a population-based case-control study of 2,530 NPC cases and 2,595 controls in Guangdong and Guangxi, southern China, in 2010-2014. Among men, risk of NPC was significantly higher in current smokers compared with never smokers (odds ratio (OR) = 1.32, 95% confidence interval (CI): 1.14, 1.53) but not in former smokers (OR = 0.92, 95% CI: 0.73, 1.17). Risk increased with smoking intensity (per 10 cigarettes/day, OR = 1.09, 95% CI: 1.03, 1.16), smoking duration (per 10 years, OR = 1.11, 95% CI: 1.06, 1.16), and cumulative smoking (per 10 pack-years, OR = 1.08, 95% CI: 1.04, 1.12). Risk decreased with later age at smoking initiation (per year, OR = 0.97, 95% CI: 0.96, 0.98) but not greater time since smoking cessation. Exposures to passive smoking during childhood (OR = 1.24, 95% CI: 1.03, 1.48) and from a spouse during adulthood (OR = 1.30, 95% CI: 1.03, 1.63) were independently associated with increased NPC risk in never-smoking men and women, but exposure-response trends were not observed. In conclusion, active and passive tobacco smoking are associated with modestly increased risk of NPC in southern China; risk is highest among long-term smokers.