Smoking can increase nasopharyngeal carcinoma risk by repeatedly reactivating Epstein‐Barr Virus: An analysis of a prospective study in southern China

Abstract

Background The association between smoking and nasopharyngeal carcinoma ( NPC ) is still uncertain. The aim of this study was to validate smoking effect on NPC and explore if smoking can induce NPC by persistently reactivating EBV in long‐term based on a prospective cohort design. Methods A NPC screening cohort with 10 181 eligible residents in Sihui city, southern China was conducted from 2008 to 2015. The smoking habit was investigated through the trained interviewers and EBV antibodies ( VCA ‐IgA, EBNA 1‐IgA) as screening markers were tested periodically. New NPC cases were identified through local cancer registry. Cox's regression model was used to estimate the adjusted hazard ratios ( aHR s) of smoking on NPC incidence. In the non‐ NPC participants, the associations between smoking and EBV seropositivity in different periods were assessed by logistic regression and generalized estimating equations ( GEE ). Results With a median of 7.54 years, 71 NPC s were diagnosed ≥1 year after recruitment. Compared with never smokers, the aHR s of developing NPC among ever smokers were 3.00 (95% CI : 1.46‐6.16). Stratified by sex, the HR s of ever smoking were 2.59 (95% CI : 1.07‐6.23) for male and 3.75 (95% CI : 1.25‐11.20) for female, respectively. Among the non‐ NPC individuals, ever smoking was not only associated with EBV seropositivity at baseline, but also in the 3‐5 years of follow up, with adjusted odds ratios ( aOR s) of 1.68 (95% CI : 1.29‐2.18) for VCA ‐IgA and 1.92 (95% CI : 1.42‐2.59) for EBNA 1‐IgA. Among the smokers who were tested EBV antibodies at least twice, the similar results were obtained using GEE. Conclusion Smoking could significantly increase the long‐term risk of NPC in southern China, partly by persistently reactivating EBV .

Association Between Serum Cotinine Level and Serological Markers of Epstein–Barr Virus in Healthy Subjects in South China Where Nasopharyngeal Carcinoma Is Endemic

“…Further research on a larger sample size (at least 1,129 subjects, with 80% power) is warranted. Indeed, a recent prospective cohort study on 10,181 residents in Sihui city (27), southern China, showed that in non-NPC subjects, ever smokers were associated with higher odds of EBV seropositivity at baseline (VCA-IgA: adjusted OR = 1.40, 95% CI = 1.22–1.60; EBNA1-IgA: 1.58, 1.38–1.82), and in the 3–5 years of follow up (VCA-IgA: 1.68, 1.29–2.18; EBNA1-IgA: 1.92, 1.42–2.59).…”

Associations between environmental factors and serological Epstein‐Barr virus antibodies in patients with nasopharyngeal carcinoma in South China

“…Evidence from large perspective epidemiological studies has suggested that elevated antibodies could be detected 5‐10 years preceding NPC diagnosis and NPC risk could increase by 20‐30 times in people with elevated levels of EBV antibodies . Several serological EBV antibodies, such as VCA‐IgA, EA‐IgA, and ENBA1‐IgA have served as the effective biomarkers in the screening of NPC in endemic areas for decades . Moreover, serological profiles of EBV have been evidenced in clinical practice to be indicative of tumor burden, treatment response and prognosis of NPC patients .…”

Smoking and Epstein–Barr virus infection in multiple sclerosis development

“…The virus may be reactivated during periods of environmental stress, whereby the EBV antibodies against viral antigens become elevated. Smokers have higher levels of anti-EBV antibodies 26,27 and higher EBV viral load 28,29 compared to nonsmokers, and several studies indicate that smoking may trigger EBV reactivation 30,31 .…”