Dose-Response Reduction in Risk of Nasopharyngeal Carcinoma From Smoking Cessation: A Multicenter Case-Control Study in Hong Kong, China.

BACKGROUND: Cigarette smoking is associated with nasopharyngeal cancer (NPC) risk. Whether quitting reduces the risk is unclear. We investigated the associations of NPC with duration of and age at quitting in an endemic region. METHODS: We investigated the associations between NPC and quitting in a multicenter case-control study in Hong Kong with 676 newly diagnosed NPC cases and 1,285 hospital controls between 2014 and 2017, using a computer-assisted self-administered questionnaire. Multivariable unconditional logistic regression yielded adjusted odds ratios (AORs) of NPC by quitting status, duration and age of quitting, combinations of duration and age of quitting, and quitting to smoking duration ratio, compared with current smoking. RESULTS: Quitting (AOR: 0.72; 95% CI: 0.53-0.98) and never smoking (0.73, 0.56-0.95) were associated with lower NPC risk. NPC risk decreased with (i) longer quitting duration (p < 0.01), reaching significance after 11-20 (0.62, 0.39-0.99) and 21+ years (0.54, 0.31-0.92) of quitting; (ii) younger quitting age (p = 0.01), reaching significance for quitting at <25 years (0.49, 0.24-0.97); and (iii) higher quitting to smoking duration ratio (p < 0.01), reaching significance when the ratio reached 1 (0.60, 0.39-0.93). Quitting younger (age <25) appeared to confer larger reductions (49% for ≤10 years of quitting, 50% for 11+ years) in NPC risk than quitting at older ages (25+) regardless of quitting duration (16% for ≤10 years, 39% for 11+ years). CONCLUSIONS: We have shown longer duration and younger age of quitting were associated with lower NPC risk, with dose-response relations. Our findings support including smoking as a cause of NPC. Stronger tobacco control measures and quitting services are needed to prevent NPC.

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

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 case-control 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 (2014-2017). 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 (Ptrend = 0.003), and a positive association in those with low socioeconomic status across categories based on the genetic score (Ptrend = 0.005). In addition, risk of NPC diagnosed at an early stage was higher for genetically lower 25OHD level (adjusted OR = 3.09, 95% CI = 1.04-9.21, Ptrend = 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.

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

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.

Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups.

Systemic lupus erythematosus (SLE), a worldwide autoimmune disease with high heritability, shows differences in prevalence, severity and age of onset among different ancestral groups. Previous genetic studies have focused more on European populations, which appear to be the least affected. Consequently, the genetic variations that underlie the commonalities, differences and treatment options in SLE among ancestral groups have not been well elucidated. To address this, we undertake a genome-wide association study, increasing the sample size of Chinese populations to the level of existing European studies. Thirty-eight novel SLE-associated loci and incomplete sharing of genetic architecture are identified. In addition to the human leukocyte antigen (HLA) region, nine disease loci show clear ancestral differences and implicate antibody production as a potential mechanism for differences in disease manifestation. Polygenic risk scores perform significantly better when trained on ancestry-matched data sets. These analyses help to reveal the genetic basis for disparities in SLE among ancestral groups.

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

BACKGROUND: We investigated the relationship of Epstein-Barr virus viral capsid antigen (EBV VCA-IgA) serostatus with ambient and personal ultraviolet radiation (UVR) and vitamin D exposure. METHODS: Using data from a multicenter case-control study, we included 1026 controls subjects in 2014-2017 in Hong Kong, China. Odds ratios (ORs) and 95% confidence intervals (CIs) of the association between UVR exposure and EBV VCA-IgA (seropositivity vs seronegativity) were calculated using unconditional logistic regression models adjusted for potential confounders. RESULTS: We observed a large increase in seropositivity of EBV VCA-IgA in association with duration of sunlight exposures at both 10 years before recruitment and age 19-30 years (adjusted OR = 3.59, 95% CI = 1.46-8.77; and adjusted OR = 2.44, 95% CI = 1.04-5.73 for ≥8 vs <2 hours/day; P for trend = .005 and .048, respectively). However, no association of EBV VCA-IgA serostatus with other indicators of UVR exposure was found. In addition, both circulating 25-hydroxyvitamin D (25OHD) and genetic predicted 25OHD were not associated with EBV VCA-IgA serostatus. CONCLUSIONS: Our results suggest that personal UVR exposure may be associated with higher risk of EBV reactivation, but we did not find clear evidence of vitamin D exposure (observational or genetic), a molecular mediator of UVR exposure. Further prospective studies in other populations are needed to confirm this finding and to explore the underlying biological mechanisms. Information on photosensitizing agents, and serological markers of EBV, and biomarkers related to systemic immunity and inflammation should be collected and are also highly relevant in future studies.

Milk Consumption Across Life Periods in Relation to Lower Risk of Nasopharyngeal Carcinoma: A Multicentre Case-Control Study.

Background: The much higher incidence of nasopharyngeal carcinoma (NPC) in men suggests sex hormones as a risk factor, and dairy products contain measurable amounts of steroid hormones. Milk consumption has greatly increased in endemic regions of NPC. We investigated the association between NPC and milk consumption across life periods in Hong Kong. Methods: A multicentre case-control study included 815 histologically confirmed NPC incident cases and 1,502 controls who were frequency-matched on age and sex at five major hospitals in Hong Kong in 2014-2017. Odds ratios (ORs) of NPC (cases vs. controls) for milk consumption at different life periods were estimated by unconditional logistic regression, adjusting for sex, age, socioeconomic status score, smoking and alcohol drinking status, exposure to occupational hazards, family history of cancer, IgA against Epstein-Barr virus viral capsid antigen, and total energy intake. Results: Compared with abstainers, lower risks of NPC were consistently observed in regular users (consuming ≥5 glasses of milk [fresh and powdered combined] per month) across four life periods of age 6-12 (adjusted OR 0.74, 95% CI 0.54-0.86), 13-18 (0.68, 0.55-0.84), 19-30 (0.68, 0.55-0.84), and 10 years before recruitment (0.72, 0.59-0.87). Long-term average milk consumption of ≤2.5, >2.5, and ≤12.5, >12.5 glasses per month yielded adjusted OR (95% CI) of 1.00 (0.80-1.26), 0.98 (0.81-1.18), 0.95 (0.76-1.18), and 0.55 (0.43-0.70), respectively (all P-values for trend < 0.05). Conclusion: Consumption of milk across life periods was associated with lower risks of NPC. If confirmed to be causal, this has important implications for dairy product consumption and prevention of NPC.

Test-retest reliability of a computer-assisted self-administered questionnaire on early life exposure in a nasopharyngeal carcinoma case-control study.

We evaluated the reliability of early life nasopharyngeal carcinoma (NPC) aetiology factors in the questionnaire of an NPC case-control study in Hong Kong during 2014-2017. 140 subjects aged 18+ completed the same computer-assisted questionnaire twice, separated by at least 2 weeks. The questionnaire included most known NPC aetiology factors and the present analysis focused on early life exposure. Test-retest reliability of all the 285 questionnaire items was assessed in all subjects and in 5 subgroups defined by cases/controls, sex, time between 1st and 2nd questionnaire (2-29/≥30 weeks), education (secondary or less/postsecondary), and age (25-44/45-59/60+ years) at the first questionnaire. The reliability of items on dietary habits, body figure, skin tone and sun exposure in early life periods (age 6-12 and 13-18) was moderate-to-almost perfect, and most other items had fair-to-substantial reliability in all life periods (age 6-12, 13-18 and 19-30, and 10 years ago). Differences in reliability by strata of the 5 subgroups were only observed in a few items. This study is the first to report the reliability of an NPC questionnaire, and make the questionnaire available online. Overall, our questionnaire had acceptable reliability, suggesting that previous NPC study results on the same risk factors would have similar reliability.

Smoking and nasopharyngeal carcinoma mortality: a cohort study of 101,823 adults in Guangzhou, China.

BACKGROUND: Nasopharyngeal carcinoma (NPC), also known as Cantonese cancer, is rare worldwide, but has particularly high incidence in North Africa and Southeast Asia, especially in Guangdong, China, such as Guangzhou. Tobacco causes head and neck cancers, but nasopharyngeal carcinoma is not included as causally related to smoking in the 2014 United States Surgeon General's report. Prospective evidence remains limited. We used Guangzhou Occupational Cohort data to conduct the first and robust prospective study on smoking and NPC mortality in an NPC high-risk region. METHODS: Information on demographic characteristics and smoking status was collected through occupational health examinations in factories and driver examination stations from March 1988 to December 1992. Vital status and causes of deaths were retrieved until the end of 1999. Cox proportional hazard model was used to assess the association of smoking with NPC mortality. RESULTS: Of 101,823 subjects included for the present analysis, 34 NPC deaths occurred during the average 7.3 years of follow up. The mean age (standard deviation) of the subjects was 41 (5.7) years. Compared with never smokers, the hazard ratio (HR) of NPC mortality was 2.95 (95% confidence interval 1.01-8.68; p=0.048) for daily smokers and 4.03 (1.29-12.58; p=0.016) for smokers with more than 10 pack-years of cumulative consumption, after adjusting for age, sex, education, drinking status, occupation and cohort status and accounting for smoking-drinking interaction. The risk of NPC mortality increased significantly with cigarettes per day (p for trend=0.01) and number of pack-years (p for trend=0.02). CONCLUSIONS: In this first and largest cohort in a high NPC risk region, smoking was associated with higher NPC mortality. The findings have shown statistically significant dose-response trend between smoking amount and smoking cumulative consumption and the risk of NPC mortality, but due to the small event number, further studies with larger sample size are needed to confirm the findings in the present study. Our results support that smoking is one of the risk factors likely to be causally associated with NPC mortality.

Tetra-aqua-bis(2-methyl-benzimidazolium-1,3-diacetato-κO)zinc(II) tetra-hydrate.

The asymmetric unit of the title compound, [Zn(C(12)H(11)N(2)O(4))(2)(H(2)O)(4)]·4H(2)O, contains one-half of the complex mol-ecule and two uncoordin-ated water mol-ecules. The four water O atoms in the equatorial plane around the Zn(II) centre ( symmetry) form a distorted square-planar arrangement, while the distorted octa-hedral coordination geometry is completed by the O atoms of the zwitterionic 2-methyl-benzimidazolium-1,3-diacetate ligands in the axial positions. The benzimidazole ring system is planar, with a maximum deviation of 0.041 (3) Å. Intra-molecular O-H⋯O hydrogen bonding results in the formation of a non-planar six-membered ring. In the crystal structure, strong intra- and inter-molecular O-H⋯O hydrogen bonds link the mol-ecules into a three-dimensional network. π-π contacts between benzimidazole rings [centroid-centroid distance = 3.899 (1) Å] may further stabilize the structure.

Bis[4-(2-hydroxy-benzyl-ideneamino)benzoato-κO]tetrakis-(methanol-κO)manganese(II).

In the title mononuclear complex, [Mn(C(14)H(10)NO(3))(2)(CH(3)OH)(4)], the Mn(II) atom, lying on an inversion centre, exhibits a distorted octa-hedral geometry, defined by two O atoms from two monodentate ligands and four O atoms from four methanol mol-ecules. The crystal structure involves intra-molecular O-H⋯N and O-H⋯O and inter-molecular O-H⋯O hydrogen bonds.

[µ-N,N,N',N'-Tetra-kis(diphenyl-phosphino-meth-yl)benzene-1,4-diamine-κP,P':P'',P''']bis-[bis-(nitrato-κO)palladium(II)].

The asymmetric unit of the title complex, [Pd(2)(NO(3))(4)(C(58)H(52)N(2)P(4))], contains one half-mol-ecule, in which the central benzene ring is located on a crystallographic centre of inversion. The Pd atom has a distorted square-planar coordination consisting of two P and two O atoms. In the crystal structure, inter-molecular C-H⋯O inter-actions link the mol-ecules into chains, and π-π contacts between the phenyl rings [centroid-centroid distance = 3.928 (3) Å] may further stabilize the structure.