Solar Ultraviolet Radiation and Vitamin D Deficiency on Epstein-Barr Virus Reactivation: Observational and Genetic Evidence From a Nasopharyngeal Carcinoma-Endemic Population

Mai, Zhi‐Ming; Lin, Jing‐Ying; Ngan, Roger K.C.; Kwong, Dora Lai-Wan; Ng, Wai‐Tong; Ng, Aik Seng; Ip, Kai-Ming; Chan, Yap‐Hang; Lee, Anne W.M.; Ho, Sai-Yin; Lung, Maria Li; Lam, Tai‐Hing

doi:10.1093/ofid/ofaa426

Cited by 9 publications

(10 citation statements)

References 39 publications

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“… 32 , 34 Our case-control study in Hong Kong, China, also reported similar association between smoking and NPC with and without adjusting for salted fish intake (data not shown). 68 Although our results may be influenced by EBV infection and activation, EBV may not be a confounder but a mediator of the association between smoking and NPC. We did not collect information on reasons for quitting (whether stopped by choice or because of illness).…”

Section: Discussionmentioning

confidence: 67%

Smoking and nasopharyngeal cancer: individual data meta-analysis of six prospective studies on 334 935 men

Lin

Wen

Jiang

et al. 2021

International Journal of Epidemiology

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Background The role of smoking in nasopharyngeal carcinoma (NPC) remains uncertain, especially in endemic regions. We conducted an individual participant data (IPD) meta-analysis of prospective cohort studies to investigate the associations between smoking exposure and risk of NPC. Methods We obtained individual participant data of 334 935 male participants from six eligible population-based cohorts in NPC-endemic regions, including two each in Guangzhou and Taiwan, and one each in Hong Kong and Singapore. We used one- and two-stage approaches IPD meta-analysis and Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of NPC for smoking exposure adjusting for age and drinking status. Results During 2 961 315 person-years of follow-up, 399 NPC evens were ascertained. Risks of NPC were higher in ever versus never smokers (HRone-stage = 1.32, 95% CI = 1.07-1.63, P = 0.0088; HRtwo-stage = 1.27, 1.01-1.60, 0.04). These positive associations appeared to be stronger in ever smokers who consumed 16+ cigarettes/day (HRone-stage = 1.67, 95% CI = 1.29-2.16, P = 0.0001), and in those who started smoking at age younger than 16 (2.16, 1.33-3.50, 0.0103), with dose-response relationships (P-values for trend = 0.0028 and 0.0103, respectively). Quitting (versus daily smoking) showed a small reduced risk (stopped for 5+ years: HRone-stage = 0.91, 95% CI = 0.60-1.39, P = 0.66; for former smokers: HRtwo-stage = 0.84, 0.61-1.14, 0.26). Conclusions This first IPD meta-analysis from six prospective cohorts in endemic regions has provided robust observational evidence that smoking increased NPC risk in men. NPC should be added to the 12–16 cancer sites known to be tobacco-related cancers. Strong tobacco control policies, preventing young individuals from smoking, would reduce NPC risk in endemic regions.

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Section: Discussionmentioning

confidence: 67%

Smoking and nasopharyngeal cancer: individual data meta-analysis of six prospective studies on 334 935 men

Lin

Wen

Jiang

et al. 2021

International Journal of Epidemiology

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“…The intraassay coefficient of variation was 4.3-8.1% by repeating measurements of 50 samples, and the reliability coefficient was acceptable (< 10%). Circulating 25OHD was classified into three a priori categorizes based on clinically relevant cut-off points for the main analysis: < 37.5 (deficient), 37.5 < 75 (insufficient), and ≥ 75 (sufficient) nmol/L [31].…”

Section: Covariate Assessmentmentioning

confidence: 99%

Dietary fiber intake from fresh and preserved food and risk of nasopharyngeal carcinoma: observational evidence from a Chinese population

Mai

Ngan

Kwong

et al. 2021

Nutr J

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Background The role of dietary fiber intake on risk of nasopharyngeal carcinoma (NPC) remains unclear. We examined the associations of dietary fiber intake on the risk of NPC adjusting for a comprehensive list of potential confounders. Methods Using data from a multicenter case-control study, we included 815 histologically confirmed NPC incident cases and 1502 controls in Hong Kong, China recruited in 2014–2017. Odds ratios (ORs) of NPC (cases vs controls) for dietary fiber intake from different sources at different life periods (age 13–18, age 19–30, and 10 years before recruitment) were evaluated using unconditional logistic regression, adjusting for sex, age, socioeconomic status, smoking and drinking status, occupational hazards, family history of cancer, salted fish, and total energy intake in Model 1, Epstein-Barr virus viral capsid antigen serological status in Model 2, and duration of sun exposure and circulating 25-hydroxyvitamin D in Model 3. Results Higher intake of total dietary fiber 10 years before recruitment was significantly associated with decreased NPC risk, with demonstrable dose-response relationship (P-values for trend = 0.001, 0.020 and 0.024 in Models 1–3, respectively). The adjusted ORs (95% CI) in the highest versus the lowest quartile were 0.51 (0.38–0.69) in Model 1, 0.48 (0.33–0.69) in Model 2, and 0.48 (0.33–0.70) in Model 3. However, the association was less clear after adjustment of other potential confounders (e.g. EBV) in the two younger periods (age of 13–18 and 19–30 years). Risks of NPC were significantly lower for dietary fiber intake from fresh vegetables and fruits and soybean products over all three periods, with dose-response relationships observed in all Models (P-values for trend for age 13–18, age 19–30 and 10 years before recruitment were, respectively, 0.002, 0.009 and 0.001 for Model1; 0.020, 0.031 and 0.003 for Model 2; and 0.022, 0.037 and 0.004 for Model 3). No clear association of NPC risk with dietary fiber intake from preserved vegetables, fruits and condiments was observed. Conclusion Our study has shown the protective role of dietary fiber from fresh food items in NPC risk, but no association for total dietary fiber intake was observed, probably because total intake also included intake of preserved food. Further studies with detailed dietary information and in prospective settings are needed to confirm this finding, and to explore the possible underlying biological mechanisms.

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“…We also hypothesized vitamin D exposure was associated with EBV reactivation. Indeed, our recent study found higher sunlight exposure was associated with EBV VCA-IgA seropositivity in our hospital controls, but circulating 25OHD and genetic predicted 25OHD levels were not associated with EBV VCA-IgA serostatus [26]. The association between UVR and NPC may be positive via EBV reactivation due to UVR-induced immunosuppression [48].…”

Section: Discussionmentioning

confidence: 62%

“…European studies in patients with multiple sclerosis reported inverse associations between vitamin D exposure and EBV serostatus [23e25]. Our recent study [26] showed personal UVR was associated with EBV viral capsid antigen (VCA-IgA) seropositivity, but not with observational or genetic 25-hydroxyvitamin D (25OHD) levels in Hong Kong, where UVR levels are high due to its latitude (22.3 N) yet vitamin D deficiency is common [27]. Given the close relation between EBV and NPC, we hypothesized vitamin D deficiency could have a role in the etiology of NPC.…”

Section: Introductionmentioning

confidence: 50%

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Low vitamin D exposure and risk of nasopharyngeal carcinoma: Observational and genetic evidence from a multicenter case–control study

Mai

Ngan

et al. 2021

Clinical Nutrition

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Background & aims: Little is known about the risk of nasopharyngeal carcinoma (NPC) in relation to vitamin D exposure. The aim of this study was to examine the associations of NPC risk with serum level of 25-hydroxyvitamin D (25OHD) and genetic predicted 25OHD, and potential effect modification by several putative risk factors of NPC. Methods: Our multicenter caseecontrol study in Hong Kong recruited 815 NPC cases and 1502 frequency-matched (by sex and age) hospital controls from five major regional hospitals, and recruited 299 healthy subjects from blood donation centers (2014e2017). Circulating level of 25-hydroxyvitamin D (25OHD) and genetic predicted 25OHD (rs12785878, rs11234027, rs12794714, rs4588 and rs6013897) were measured by validated enzyme immunoassay and the iPLEX assay on the MassARRAY System, respectively. Data were also collected on demographics, lifestyle factors, ultraviolet radiation exposure, and potential confounders using a computer-assisted, self-administered questionnaire with satisfactory test-retest reliability. Unconditional logistic regression models were used to estimate ORs and 95% CIs. Results: Despite no significant association of NPC risk with circulating 25OHD and genetic predicted 25OHD, there was evidence for an inverse association in participants with normal body mass index (between 18.5 and 27.5) across categories of 25OHD (P trend ¼ 0.003), and a positive association in those with low socioeconomic status across categories based on the genetic score (P trend ¼ 0.005). In addition, risk of NPC diagnosed at an early stage was higher for genetically lower 25OHD level (adjusted OR ¼ 3.09, 95% CI ¼ 1.04e9.21, P trend ¼ 0.022). Conclusions: Findings of this first comprehensive study to investigate the positive association of NPC risk with vitamin D deficiency need to be confirmed and be best interpreted with results of further similar studies. Our findings may inform possible etiological mechanisms of the associations with several putative risk/protective factors of NPC.

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Solar Ultraviolet Radiation and Vitamin D Deficiency on Epstein-Barr Virus Reactivation: Observational and Genetic Evidence From a Nasopharyngeal Carcinoma-Endemic Population

Cited by 9 publications

References 39 publications

Smoking and nasopharyngeal cancer: individual data meta-analysis of six prospective studies on 334 935 men

Smoking and nasopharyngeal cancer: individual data meta-analysis of six prospective studies on 334 935 men

Dietary fiber intake from fresh and preserved food and risk of nasopharyngeal carcinoma: observational evidence from a Chinese population

Low vitamin D exposure and risk of nasopharyngeal carcinoma: Observational and genetic evidence from a multicenter case–control study

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