Abstract
Introduction: Self-reported smoking has been associated with higher seropositivity for the IgA response to Epstein–Barr virus (EBV) viral capsid antigen (VCA-IgA) and transcription activator protein (Zta) in healthy men in southern China where nasopharyngeal carcinoma (NPC) is endemic. Results on the association of biochemically verified smoking status with EBV reactivation are scarce. We aimed to investigate the relations of serum cotinine level with serological markers of EBV in healthy women, in addition to men.Methods: We collected information on demographic, lifestyle, environmental factors, and EBV serological markers in a cross-sectional study on 2,275 healthy subjects who were recruited from physical examination centers in Guangdong Province, China. In the present analysis, 901 subjects' serum cotinine levels have been measured by enzyme-linked immunosorbent assay (ELISA). Odds ratios (seropositivity of four EBV serological markers vs. seronegativity) for categorical serum cotinine levels were calculated by unconditional logistic regression with a group-specific confidence interval (CI).Results: In women, compared with lower serum cotinine level (0–0.71 ng/ml), higher cotinine level (>0.71–1.20 ng/ml; >1.20–228.40 ng/ml) was associated but non-significantly with higher seropositivity for EBV VCA-IgA (age- and education-adjusted OR = 1.18, 95% CIs = 0.84–1.64, 1.06, 0.75–1.50). These associations remained but still non-significant after adjusting for 5-year age group, education, family history of cancer, consumption of tea, Chinese herbal tea, salted fish at childhood, and exposure to occupational dust, chemical, fume, and radiation (multivariable adjusted OR = 1.21, 95% CIs = 0.85–1.71, 1.09, 0.76–1.55). In men, compared with lower serum cotinine level (0–2.15 ng/ml), higher cotinine level (>2.15–103.6 ng/ml; >103.6–419.4 ng/ml) was significantly associated with higher seropositivity for EBV VCA-IgA and Zta-IgA (age- and education-adjusted OR = 2.16, 95% CIs = 1.37–3.41, 1.79, 1.11–2.90; 1.98, 1.17–3.34, 1.95, 1.14–3.34). The association remained significant after adjusting for potential confounders for Zta-IgA (OR = 2.32, 95% CI = 1.37–3.93 for >2.15–103.6, and 2.50, 1.43–4.38 for >103.6–419.4 ng/ml), but not for VCA-IgA (2.06, 1.29–3.27, and 1.61, 0.96–2.71).Conclusions: Higher serum cotinine level is associated with higher seropositivity for EBV serological markers in healthy men in southern China. Such positive association was also observed in women but became non-significant. If confirmed to be causal, this finding has important implications for tobacco control and prevention of EBV-related disease, particularly for NPC.
Highlights
Self-reported smoking has been associated with higher seropositivity for the IgA response to Epstein–Barr virus (EBV) viral capsid antigen (VCA-IgA) and transcription activator protein (Zta) in healthy men in southern China where nasopharyngeal carcinoma (NPC) is endemic
EBV has been rated as a Group 1 carcinogen by the International Agency for Research on Cancer, because of its association with nasopharyngeal carcinoma (NPC) [2]
NPC remains very rare in the world, except southern China, suggesting reactivation of EBV is necessary in the pathogenesis of NPC [4]
Summary
Self-reported smoking has been associated with higher seropositivity for the IgA response to Epstein–Barr virus (EBV) viral capsid antigen (VCA-IgA) and transcription activator protein (Zta) in healthy men in southern China where nasopharyngeal carcinoma (NPC) is endemic. Our previous study has first reported that self-reported smoking initiation at younger age and higher cumulative amount of smoking (vs never smoking) were associated with higher seropositivity for the IgA response to viral capsid antigen (VCA-IgA) in healthy men in Guangdong province, southern China where NPC is endemic [5]. Our recent study has shown that self-reported smoking was associated with higher levels of other EBV antibodies (EBNA1-IgA and BZLF1 transcription activator protein [Zta-IgA]) in the same population [6]. The validity of self-reported smoking is often questioned because of the common belief that smokers are inclined to underestimate the amount smoked or to deny smoking at all [9], in women in China where smoking is usually socially undesirable [10]
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