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 population-based 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.

Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) are ubiquitous synthetic chemicals with no known effect on human cancer development. This article systematically and critically reviews the epidemiologic evidence regarding the association between PFOA and PFOS exposure and cancer risk in humans. Eighteen epidemiologic studies – eight of PFOA, four of PFOS, and six of both PFOA and PFOS – have estimated associations of exposure to these chemicals with cancer incidence or mortality, with studies equally divided between occupational and nonoccupational settings. Although some statistically significant positive associations have been reported, for example, with cancers of the prostate, kidney, testis, and thyroid, the majority of relative risk estimates for both PFOA and PFOS have been between 0.5 and 2.0 (with 95% confidence intervals including 1.0), inconsistently detected across studies, counterbalanced by negative associations, not indicative of a monotonic exposure-response relationship, and not coherent with toxicological evidence in animals, in which the primary target organs are the liver, testis (Leydig cells), and pancreas (acinar cells). Many positive associations with PFOA exposure were detected in community settings without occupational exposure and were not supported by results in exposed workers. Given that occupational exposure to PFOA and PFOS is one to two orders of magnitude higher than environmental exposure, the discrepant positive findings are likely due to chance, confounding, and/or bias. Taken together, the epidemiologic evidence does not support the hypothesis of a causal association between PFOA or PFOS exposure and cancer in humans.

Whether perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS), two widely used and biopersistent synthetic chemicals, are immunotoxic in humans is unclear. Accordingly, this article systematically and critically reviews the epidemiologic evidence on the association between exposure to PFOA and PFOS and various immune-related health conditions in humans. Twenty-four epidemiologic studies have reported associations of PFOA and/or PFOS with immune-related health conditions, including ten studies of immune biomarker levels or gene expression patterns, ten studies of atopic or allergic disorders, five studies of infectious diseases, four studies of vaccine responses, and five studies of chronic inflammatory or autoimmune conditions (with several studies evaluating multiple endpoints). Asthma, the most commonly studied condition, was evaluated in seven studies. With few, often methodologically limited studies of any particular health condition, generally inconsistent results, and an inability to exclude confounding, bias, or chance as an explanation for observed associations, the available epidemiologic evidence is insufficient to reach a conclusion about a causal relationship between exposure to PFOA and PFOS and any immune-related health condition in humans. When interpreting such studies, an immunodeficiency should not be presumed to exist when there is no evidence of a clinical abnormality. Large, prospective studies with repeated exposure assessment in independent populations are needed to confirm some suggestive associations with certain endpoints.

The current World Health Organization (WHO) classification of nasopharyngeal carcinoma (NPC) conveys little prognostic information. This study aimed to propose an NPC histopathologic classification that can potentially be used to predict prognosis and treatment response. We initially developed a histopathologic classification based on the morphologic traits and cell differentiation of tumors of 2716 NPC patients who were identified at Sun Yat-sen University Cancer Center (SYSUCC) (training cohort). Then, the proposed classification was applied to 1702 patients (retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients (prospective validation cohort) from SYSUCC. The efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes. We used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS). The 5-year OS rates for all NPC patients who were diagnosed with epithelial carcinoma (EC; 3708 patients), mixed sarcomatoid-epithelial carcinoma (MSEC; 1247 patients), sarcomatoid carcinoma (SC; 823 patients), and squamous cell carcinoma (SCC; 253 patients) were 79.4%, 70.5%, 59.6%, and 42.6%, respectively (P < 0.001). In multivariate models, patients with MSEC had a shorter OS than patients with EC (HR = 1.44, 95% CI = 1.27–1.62), SC (HR = 2.00, 95% CI = 1.76–2.28), or SCC (HR = 4.23, 95% CI = 3.34–5.38). Radiochemotherapy significantly improved survival compared with radiotherapy alone for patients with EC (HR = 0.67, 95% CI = 0.56–0.80), MSEC (HR = 0.58, 95% CI = 0.49–0.75), and possibly for those with SCC (HR = 0.63; 95% CI = 0.40–0.98), but not for patients with SC (HR = 0.97, 95% CI = 0.74–1.28). The proposed classification offers more information for the prediction of NPC prognosis compared with the WHO classification and might be a valuable tool to guide treatment decisions for subtypes that are associated with a poor prognosis.

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.

Background: Better understanding about gastric cancer incidence patterns among Hispanics by birthplace, socioeconomic status (SES), and acculturation can improve preventive strategies and disease models. Methods: Incidence rates, rate ratios, and estimated annual percent change (EAPC) in rates of anatomic and histologic subtype-specific gastric cancer were calculated by age, sex, and nativity among Hispanics using California Cancer Registry data from 1988 through 2004. Incidence rates in 1998 to 2002 were compared by neighborhood SES and Hispanic enclave status according to 2000 US Census data. Results: Incidence rates of diffuse gastric cancer increased from 1988 through 2004 among foreign-born Hispanic men (EAPC: 3.5%, 95% CI: 1.5%–5.5%) and U.S.-born Hispanic women (EAPC: 3.0%, 95% CI: 0.7%–5.3%). During the same time period, incidence rates of intestinal gastric cancer declined significantly and both cardia and noncardia gastric cancer were steady or declined among foreign-born and U.S.-born Hispanic men and women. Noncardia and both intestinal and diffuse gastric cancer were more common in foreign-born than U.S.-born Hispanic men and women, and in those from lower SES, higher enclave neighborhoods. By contrast, among younger and middle-aged Hispanic men, cardia tumors were more common in the U.S.-born than the foreign-born, and in higher SES, lower enclave neighborhoods. Conclusions: Varying gastric cancer risk factors among Hispanic subgroups and increasing rates of diffuse gastric cancer in foreign-born Hispanic men and U.S.-born Hispanic women merit further investigation to identify separate disease etiologies. Impact: Age, sex, birthplace, SES, and acculturation modify gastric cancer incidence in Hispanics and should be considered when examining disease risk and prevention. Cancer Epidemiol Biomarkers Prev; 21(5); 709–19. ©2012 AACR.