High-throughput identification of regulatory elements and functional assays to uncover susceptibility genes for nasopharyngeal carcinoma.

Large-scale genetic association studies have identified multiple susceptibility loci for nasopharyngeal carcinoma (NPC), but the underlying biological mechanisms remain to be explored. To gain insights into the genetic etiology of NPC, we conducted a follow-up study encompassing 6,907 cases and 10,472 controls and identified two additional NPC susceptibility loci, 9q22.33 (rs1867277; OR = 0.74, 95% CI = 0.68-0.81, p = 3.08 × 10-11) and 17q12 (rs226241; OR = 1.42, 95% CI = 1.26-1.60, p = 1.62 × 10-8). The two additional loci, together with two previously reported genome-wide significant loci, 5p15.33 and 9p21.3, were investigated by high-throughput sequencing for chromatin accessibility, histone modification, and promoter capture Hi-C (PCHi-C) profiling. Using luciferase reporter assays and CRISPR interference (CRISPRi) to validate the functional profiling, we identified PHF2 at locus 9q22.33 as a susceptibility gene. PHF2 encodes a histone demethylase and acts as a tumor suppressor. The risk alleles of the functional SNPs reduced the expression of the target gene PHF2 by inhibiting the enhancer activity of its long-range (4.3 Mb) cis-regulatory element, which promoted proliferation of NPC cells. In addition, we identified CDKN2B-AS1 as a susceptibility gene at locus 9p21.3, and the NPC risk allele of the functional SNP rs2069418 promoted the expression of CDKN2B-AS1 by increasing its enhancer activity. The overexpression of CDKN2B-AS1 facilitated proliferation of NPC cells. In summary, we identified functional SNPs and NPC susceptibility genes, which provides additional explanations for the genetic association signals and helps to uncover the underlying genetic etiology of NPC development.

Skipping Breakfast and Eating Breakfast Away From Home Were Prospectively Associated With Emotional and Behavioral Problems in 115,217 Chinese Adolescents.

BACKGROUND: Breakfast is deemed the most important meal of the day. We examined the prospective associations of breakfast habits with emotional/behavioral problems in adolescents and potential effect modification. METHODS: 115,217 Primary 6 students (United States Grade 6; mean age, 11.9; standard deviation [SD], 0.59 years) who attended the Student Health Service of Department of Health in Hong Kong in 2004/05, 2006/07, 2008/09 were followed till Secondary 6 (United States Grade 12). Emotional/behavioral problems were biennially examined using Youth Self-Report since Secondary 2 (United States Grade 8). Lifestyles were biennially examined using standardized questionnaires since Primary 6. Prospective associations of breakfast habit with emotional/behavioral problems and potential effect modification were examined using generalized estimating equations. RESULTS: Compared with eating breakfast at home, eating breakfast away from home was significantly associated with total emotional/behavioral problems and seven syndromes, including withdrawal, somatic complaints, anxiety/depression, thought problems, attention problems, delinquent behaviors, and aggressive behaviors (adjusted odds ratios [AORs] 1.22-2.04), while skipping breakfast showed stronger associations with the above problems and social problems (AORs 1.34-2.29). Stronger associations were observed in younger students for total and attention problems (P < 0.03) and in those with lower weight status for delinquent behaviors (P = 0.005). CONCLUSION: Eating breakfast away from home and especially skipping breakfast were prospectively associated with adolescent emotional/behavioral problems. The associations weakened with increasing age for total emotional/behavioral and attention problems, and weakened with higher weight status for delinquent behaviors, highlighting the vulnerability of younger and underweight children. If the associations are causal, increasing home breakfast may reduce adolescent emotional/behavioral problems and benefit psychosocial health.

Mendelian Randomization Focused Analysis of Vitamin D on the Secondary Prevention of Ischemic Stroke.

BACKGROUND AND PURPOSE: Experimental studies showed vitamin D (Vit-D) could promote vascular regeneration and repair. Prior randomized studies had focused mainly on primary prevention. Whether Vit-D protects against ischemic stroke and myocardial infarction recurrence among subjects with prior ischemic insults was unknown. Here, we dissected through Mendelian randomization any effect of Vit-D on the secondary prevention of recurrent ischemic stroke and myocardial infarction. METHODS: Based on a genetic risk score for Vit-D constructed from a derivation cohort sample (n=5331, 45% Vit-D deficient, 89% genotyped) via high-throughput exome-chip screening of 12 prior genome-wide association study-identified genetic variants of Vit-D mechanistic pathways (rs2060793, rs4588, and rs7041; F statistic, 73; P<0.001), we performed a focused analysis on prospective recurrence of myocardial infarction (MI) and ischemic stroke in an independent subsample with established ischemic disease (n=441, all with prior first ischemic event; follow-up duration, 41.6±14.3 years) under a 2-sample, individual-data, prospective Mendelian randomization approach. RESULTS: In the ischemic disease subsample, 11.1% (n=49/441) had developed recurrent ischemic stroke or MI and 13.3% (n=58/441) had developed recurrent or de novo ischemic stroke/MI. Kaplan-Meier analyses showed that genetic risk score predicted improved event-free survival from recurrent ischemic stroke or MI (log-rank, 13.0; P=0.001). Cox regression revealed that genetic risk score independently predicted reduced risk of recurrent ischemic stroke or MI combined (hazards ratio, 0.62 [95% CI, 0.48-0.81]; P<0.001), after adjusted for potential confounders. Mendelian randomization supported that Vit-D is causally protective against the primary end points of recurrent ischemic stroke or MI (Wald estimate: odds ratio, 0.55 [95% CI, 0.35-0.81]) and any recurrent or de novo ischemic stroke/MI (odds ratio, 0.64 [95% CI, 0.42-0.91]) and recurrent MI alone (odds ratio, 0.52 [95% CI, 0.30-0.81]). CONCLUSIONS: Genetically predicted lowering in Vit-D level is causal for the recurrence of ischemic vascular events in persons with prior ischemic stroke or MI.

Higher total white blood cell and neutrophil counts are associated with an increased risk of fatal stroke occurrence: the Guangzhou biobank cohort study.

BACKGROUND: Chronic inflammatory diseases are linked to an increased risk of stroke events. The white blood cell (WBC) count is a common marker of the inflammatory response. However, it is unclear whether the WBC count, its subpopulations and their dynamic changes are related to the risk of fatal stroke in relatively healthy elderly population. METHODS: In total, 27,811 participants without a stroke history at baseline were included and followed up for a mean of 11.5 (standard deviation = 2.3) years. After review of available records, 503 stroke deaths (ischaemic 227, haemorrhagic 172 and unclassified 104) were recorded. Cox proportional hazards regression was used to assess the associations between the WBC count, its subpopulations and their dynamic changes (two-phase examination from baseline to the 1st follow-up) and the risk of fatal all stroke, fatal ischaemic stroke and fatal haemorrhagic stroke. RESULTS: (i) Regarding the WBC count in relation to the risk of fatal stroke, restricted cubic splines showed an atypically U-curved association between the WBC count and the risk of fatal all stroke occurrence. Compared with those in the lowest WBC count quartile (< 5.3*10^9/L), the participants with the highest WBC count (> 7.2*10^9/L) had a 53 and 67% increased risk for fatal all stroke (adjusted hazard ratio [aHR] = 1.53, 95% confidence interval (CI) 1.16-2.02, P = 0.003) and fatal haemorrhagic stroke (aHR = 1.67, 95% CI 1.10-2.67, P = 0.03), respectively; compared with those in the lowest quartile (< 3.0*10^9/L), the participants with the highest NEUT count (> 4.5*10^9/L) had a 45 and 65% increased risk for fatal all stroke (aHR = 1.45, 95% CI 1.10-1.89, P = 0.008) and fatal ischaemic stroke (aHR = 1.65, 95%CI 1.10-2.47 P = 0.02), respectively. With the additional adjustment for C-reactive protein, the same results as those for all stroke and ischaemic stroke, but not haemorrhagic stroke, were obtained for the WBC count (4 ~ 10*10^9/L) and the NEUT count (the NEUT counts in the top 1% and bottom 1% at baseline were excluded). (ii) Regarding dynamic changes in the WBC count in relation to the risk of fatal stroke, compared with the stable group (- 25% ~ 25%, dynamic changes from two phases of examination (baseline, from September 1st, 2003 to February 28th, 2008; 1st follow-up, from March 31st 2008 to December 31st 2012)), the groups with a 25% increase in the WBC count and NEUT count respectively had a 60% (aHR = 1.60, 95% CI 1.07-2.40, P = 0.02) and 45% (aHR = 1.45, 95% CI1.02-2.05, P = 0.04) increased risk of fatal all stroke occurrence. CONCLUSIONS: The WBC count, especially the NEUT count, was associated with an increased risk of fatal all stroke occurrence. Longitudinal changes in the WBC count and NEUT count increase in excess of 25% were also associated with an increased risk of fatal all stroke occurrence in the elderly population.

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

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.

Association of Lipids With Ischemic and Hemorrhagic Stroke: A Prospective Cohort Study Among 267 500 Chinese.

Background and Purpose- Previous results on the association between lipids and stroke were controversial. We investigated the association of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C ), high-density lipoprotein cholesterol (HDL-C), and triglyceride with stroke. Methods- Six cohort studies in China with 267 500 participants were included. Cox proportional hazards regression models and restricted cubic spline analyses were used to estimate hazard ratios and 95% CIs and explore linear and nonlinear relationships of lipids and stroke, respectively. Results- The median follow-up duration ranged from 6 to 19 years. During 2 295 881 person-years, 8072 people developed stroke. Multivariable adjusted hazard ratios (95% CIs) per 1 mmol/L increase in TC, LDL-C, triglyceride were 1.08 (1.05-1.11), 1.08 (1.04-1.11), 1.07 (1.05-1.09) for ischemic stroke, respectively. Compared with participants with TC 160-199.9 mg/dL, hazard ratios (95% CIs) were 1.43 (1.11-1.85) for hemorrhagic stroke in those with TC <120 mg/dL. Compared with participants with HDL-C 50 to 59.9 mg/dL, hazard ratios (95% CIs) were 1.23 (1.12-1.35), 1.13 (1.04-1.22) for ischemic stroke, and 1.28 (1.10-1.49), 1.17 (1.03-1.33) for hemorrhagic stroke in those with HDL-C <40 and 40 to 49.9 mg/dL, respectively. Restricted cubic spline analyses showed linear relationships of TC and LDL-C, and nonlinear relationships of HDL-C and triglyceride with ischemic stroke (all P<0.001). Hemorrhagic stroke showed linear relationships with TC and HDL-C (P=0.029 and <0.001 respectively), but no relationship with LDL-C and triglyceride (all P>0.05). Conclusions- TC, LDL-C, and triglyceride showed positive associations with ischemic stroke. The risk of hemorrhagic stroke was higher when TC was lower than 120 mg/dL. LDL-C and triglyceride showed no association with hemorrhagic stroke. The risks of ischemic and hemorrhagic stroke might be higher when HDL-C was lower than 50 mg/dL.

Increasing socioeconomic disparities in sedentary behaviors in Chinese children.

BACKGROUND: Sedentary behaviors are prevalent in Chinese children, however, the studies on their trends and socioeconomic disparities are scarce. We examined the time trends of daily television (TV) viewing and video game playing and the associated socioeconomic factors in Chinese children in Hong Kong, the most developed and westernized city in China. METHODS: In a panel data study involving 538,300 primary four and 510,294 primary six students from 1999/2000 to 2008/09, data on socioeconomic status, sedentary behaviors (TV viewing and video game playing) and other lifestyle habits were collected using a self-administered questionnaire. Trends in sedentary behaviors over time were assessed. Their socioeconomic disparities were examined by interactions in generalized estimating equations with the adjustment for weight status and extracurricular physical activities. RESULTS: The age and sex-standardized prevalence of ≥2 h daily TV viewing decreased from 51.4% (95% confidence interval [CI] 51.1-51.8%) in 1999/2000 to 43.8% (95% CI 43.4-44.2%) in 2008/09 (P for trend < 0.001), whereas that of ≥1 h daily video game playing increased from 8.2% (95% CI 7.9-8.4%) to 22.4% (95% CI 22.0-22.7%). Both sedentary behaviors were more prevalent in boys than girls, but the disparities decreased over time (Ratio of odds ratio [ROR] = 0.996 and 0.924 for TV viewing and video game playing, respectively). In contrast, both sedentary behaviors were increasingly more prevalent in children whose parents had lower education levels or non-managerial/professional occupations (ROR 1.006-1.082). CONCLUSIONS: Children in lower socioeconomic families in Hong Kong were increasingly at risk of having sedentary behaviors over years and thus deserve more attention. Effective strategies targeting children and/or their parents of lower socioeconomic status are needed to reduce sedentary behaviors.

Paternal smoking and maternal protective behaviors at home on infant's saliva cotinine levels.

BackgroundWe investigated the association between paternal smoking, avoidance behaviors and maternal protective actions and smoke-free home rules with infant's saliva cotinine in Hong Kong.MethodsSix hundred and seventy-five non-smoking mothers (mean age 32.6 years) who attended the maternal-child health clinics with their newborns aged ≤18 months completed a questionnaire about paternal smoking and avoidance behaviors, maternal protective actions, smoke-free rules at home, and infant's second-hand smoke (SHS) exposure. Three hundred and eighty-nine infants provided saliva sample and its cotinine was tested.ResultsThe geometric mean of infant's saliva cotinine was 1.07 ng/ml (95% confidence interval (CI): 0.98, 1.16). Infants living in smoking families with SHS exposure had significantly higher cotinine level than in non-smoking families (adjusted ß=0.25, 95% CI: 0.16, 0.33). Paternal smoking near infants (within 1.5 m) was associated with higher cotinine level (adjusted ß=0.60, 95% CI: 0.22, 0.98), which was not reduced by avoidance behaviors (e.g., smoking in kitchen or balcony). Even fathers smoking ≥3 m away from infants was associated with higher cotinine level than non-smoking families (adjusted ß=0. 09, 95% CI: 0.01, 0.16). Maternal protective actions and smoke-free home rules were not significantly associated with reduced cotinine level.ConclusionPaternal smoking avoidance, maternal protective actions, and smoke-free policy at home did not reduce infant's saliva cotinine.

Smoking and Mortality in Tianjin, China: A Death Registry-Based Case-Control Study, 2010-2014.

INTRODUCTION: We conducted a mortality case-control study to assess the risks of all-cause and major causes of death attributable to smoking in Tianjin from 2010 through 2014. The death registry-based study used data from The Tianjin All Causes of Death Surveillance System, which collects information routinely on smoking of the deceased in the death certificate of Tianjin Centers for Disease Control and Prevention. METHODS: Cases (n = 154,086) and controls (n = 25,476) were deaths at 35 to 79 years from smoking-related and nonsmoking-related causes, respectively. Mortality rate ratios (RRs) for ever smokers versus never smokers, with adjustment for sex, 5-year age group, education, marital status, and year of death, and smoking-attributed fractions were calculated. RESULTS: The RRs in men were 1.38 (95% confidence interval [CI], 1.33-1.43) for all causes and 3.07 (95% CI, 2.91-3.24) for lung cancer, and in women were 1.46 (95% CI, 1.39-1.54) and 4.07 (95% CI, 3.81-4.35). The smoking-attributed fractions for all causes and for lung cancer in men were 15.4% and 50.2%, respectively, and in women were 7.3% and 32.7%, respectively. Smoking annually caused an average of 3,756 (9.4%) deaths, mostly from lung cancer in men (47.4%) and women (66.9%). Women who started smoking before 30 had a higher RR (1.79; 95% CI, 1.63-1.97) than men who did so (1.48; 95% CI, 1.41-1.56). CONCLUSION: Lung cancer was the main cause of smoking-induced deaths in both sexes. Tobacco use is a major cause of premature deaths in men aged 35 to 79 years. Young women must be urged to not start smoking because they could have greater risk of all-cause and lung cancer deaths than men do.

A Brief Smoking Cessation Advice by Youth Counselors for the Smokers in the Hong Kong Quit to Win Contest 2010: a Cluster Randomized Controlled Trial.

Smoking cessation counseling by healthcare professionals is effective, but very few healthcare professionals can deliver these interventions in the busy clinical settings. This study aimed to evaluate the effectiveness of a brief smoking cessation advice delivered by briefly-trained youth counselors at the enrolment of an incentive-based smoking cessation campaign. The study design was a cluster 2-arm randomized controlled trial of 831 Chinese adult smokers who were recruited in public areas to participate in the Hong Kong Quit to Win Contest 2010. The intervention group (n = 441) received a 5-min quitting advice from the youth counselors, who were mainly undergraduate nursing students, and a 12-page self-help smoking cessation booklet at the enrolment, while the control group (n = 390) only received the same booklet. Biochemically confirmed quitters at 6-month follow-up could join a lucky draw that offered HK$10,000 (US$1282) cash prize to three winners and HK$4000 gift vouchers to the other 10 winners. Primary outcome was self-reported smoking abstinence at 6-month follow-up. By intention-to-treat, the intervention group had a non-significantly higher self-reported (18.4 versus 13.8%, OR = 1.40, 95% CI 0.96-2.04, p = 0.08) and validated quit rate (9.1 versus 6.7%, OR = 1.40, 95% CI 0.84-2.33, p = 0.20) than the control group at 6-month follow-up. The analysis with multiple imputation for missing data also found similar results. We concluded that the brief on-site advice by trained youth counselors had a modest effect on smoking cessation, but the effect was not significant. Future studies with larger sample size and results from higher participation of the biochemical validation to confirm the effectiveness are warranted.

Proactive and Brief Smoking Cessation Intervention for Smokers at Outdoor Smoking "Hotspots" in Hong Kong.

Increased outdoor smoking is a common phenomenon after indoor smoking bans were in place. A series of observational studies were conducted to evaluate a novel, proactive, and brief smoking cessation intervention at outdoor smoking "hotspots," i.e., outdoor public areas where ashtrays were available and smokers clustered to smoke. The number of smokers at 26 selected hotspots were observed and counted for two consecutive days. Further observations of the smokers' characteristics and brief smoking cessation intervention were conducted at ten of the hotspots with the greatest number of smokers. Responses of the smokers to the brief intervention, including a leaflet and brief smoking cessation advice using AWAR protocol delivered by trained smoking cessation ambassadors, were assessed. A total of 24,034 smokers were observed within 464 h, which equals 51.8 smokers per hour. Of the 5070 pedestrians observed at the ten hotspots during the intervention sessions, 1228 (24.2 %) were smokers. In the 1228 smokers who were approached during our intervention sessions, about two thirds were willing to receive the self-help leaflet on smoking cessation whereas about half received the brief smoking cessation advice. Recruiting smokers and delivering brief smoking cessation interventions at smoking hotspots are feasible and likely effective to reach large numbers of smokers. Studies to evaluate the effectiveness of using this approach for smoking cessation are warranted.

Exome-chip association analysis reveals an Asian-specific missense variant in PAX4 associated with type 2 diabetes in Chinese individuals.

AIMS/HYPOTHESIS: Genome-wide association studies (GWASs) have identified many common type 2 diabetes-associated variants, mostly at the intronic or intergenic regions. Recent advancements of exome-array genotyping platforms have opened up a novel means for detecting the associations of low-frequency or rare coding variants with type 2 diabetes. We conducted an exomechip association analysis to identify additional type 2 diabetes susceptibility variants in the Chinese population. METHODS: An exome-chip association study was conducted by genotyping 5640 Chinese individuals from Hong Kong, using a custom designed exome array, the Asian Exomechip. Single variant association analysis was conducted on 77,468 single nucleotide polymorphisms (SNPs). Fifteen SNPs were subsequently genotyped for replication analysis in an independent Chinese cohort comprising 12,362 individuals from Guangzhou. A combined analysis involving 7189 cases and 10,813 controls was performed. RESULTS: In the discovery stage, an Asian-specific coding variant rs2233580 (p.Arg192His) in PAX4, and two variants at the known loci, CDKN2B-AS1 and KCNQ1, were significantly associated with type 2 diabetes with exome-wide significance (p discovery < 6.45 × 10-7). The risk allele (T) of PAX4 rs2233580 was associated with a younger age at diabetes diagnosis. This variant was replicated in an independent cohort and demonstrated a stronger association that reached genome-wide significance (p meta-analysis [p meta] = 3.74 × 10-15) in the combined analysis. CONCLUSIONS/INTERPRETATION: We identified the association of a PAX4 Asian-specific missense variant rs2233580 with type 2 diabetes in an exome-chip association analysis, supporting the involvement of PAX4 in the pathogenesis of type 2 diabetes. Our findings suggest PAX4 is a possible effector gene of the 7q32 locus, previously identified from GWAS in Asians.

Genetically deprived vitamin D exposure predisposes to atrial fibrillation.

AIMS: Low vitamin D level is associated with atrial fibrillation (AF) and may be implicated in its pathogenesis. METHODS AND RESULTS: We studied single nucleotide polymorphisms (SNPs) of vitamin D mechanistic pathways and serum 25-hydroxyvitamin D [25(OH)D] levels in an age- and gender-matched case-control study (controls without AF: mean age 68.6 ± 8.7 years, female 25%; n = 1019; with AF: mean age 69.7 ± 9.5 years, female 30%; n = 156) recruited from a Chinese clinical cohort of patients with stable coronary artery disease. Twelve SNPs involved in the vitamin D mechanistic pathways were studied [biosynthetic: rs4646536, rs10877012, rs3829251, rs1790349; activation: rs2060793, rs1993116; vitamin D-binding protein (VBP)/group-specific component (GC): rs4588, rs7041, rs2282679, rs1155563; and vitamin D receptor: rs1544410, rs10735810]. A genetic risk score (GRS) (0-8) was constructed from SNPs associated with serum 25(OH)D as a proxy to lifelong vitamin D-deficient state. All 4 SNPs involved in the VBP/GC were significantly associated with serum 25(OH)D (rs4588, P < 0.001; rs2282679, P < 0.001; rs7041, P = 0.011; rs1155563, P < 0.001; all other SNPs, P > 0.05). Vitamin D GRS (points 0-8) generated from these 4 SNPs was independently predictive of serum 25(OH)D [B = 0.54, 95% confidence interval (CI) 0.30-0.79; P < 0.001]. Genetically deprived vitamin D status as denoted by a low GRS (0-3) independently predicted an increased risk of AF, compared to a high GRS (4-8) (odds ratio = 1.848, 95% CI 1.217-2.805; P = 0.004). CONCLUSION: Genetically deprived vitamin D exposure predisposes to increased AF among patients with coronary artery disease. Whether VBP/GC may alter the risk of AF via alternative mechanisms warrants further studies.

Online Social Support for the Prevention of Smoking Relapse: A Content Analysis of the WhatsApp and Facebook Social Groups.

BACKGROUND: Online social groups have been increasingly used for smoking cessation intervention. INTRODUCTION: This study aimed to explore the social support components of the online discussion through WhatsApp and Facebook, how these components addressed the need of relapse prevention, and how the participants evaluated this intervention. MATERIALS AND METHODS: We coded and analyzed the posts (N = 467) by the 82 recent quitters in WhatsApp and Facebook social groups, who were recruited from the eight smoking cessation clinics in Hong Kong to participate in a pragmatic randomized trial of relapse prevention. Participants' postintervention feedback was collected from the 13 qualitative interviews after the intervention. RESULTS: The WhatsApp social groups had more participants' posts than the Facebook counterparts. The participants' posts in the online social groups could be classified as sharing views and experiences (55.5%), encouragement (28.7%), and knowledge and information (15.8%). About half of the participants' posts (52.9%) addressed the themes listed in the U.S. Clinical Practice Guideline for preventing smoking relapse. The participants perceived the posts as useful reminders for smoking cessation, but avoidance of reporting relapse, inactive discussions, and uninteresting content were barriers to the success of the intervention. DISCUSSION: Online social groups provided a useful platform for the delivery of cessation support and encouragement of reporting abstinence, which support relapse prevention. The effectiveness of such intervention can be improved by encouraging more self-report of relapse, active discussions, sharing of interesting content, and using an appropriate discussion platform. CONCLUSION: Quitters who participate in the online social groups can benefit from peer support and information sharing, and hence prevent smoking relapse.

Depressive Symptoms Delayed Quit Attempts and Shortened Abstinence in Young Smokers of the Hong Kong Youth Quitline.

INTRODUCTION: Young smokers often report depressive symptoms while receiving smoking cessation counseling. This study examines time patterns in the quitting process among young smokers with or without notable depressive symptoms. METHODS: The quitting trajectories of young smokers aged 12 to 25 (n = 578) who called the Youth Quitline in Hong Kong between March 2006 and May 2011 were recorded and analyzed through multiple telephone sessions over periods of up to 6 months. The time patterns of young smokers who had or did not have notable depressive symptoms were compared using nonparametric Kaplan-Meier methods with log-rank tests. RESULTS: Among young smokers with low levels of nicotine dependence, those who had notable depressive symptoms were less likely to initiate a quit attempt within 28 days after their baseline telephone intervention (probability = .38 vs. .60; P value = .04). Furthermore, young smokers who had notable depressive symptoms were less likely to remain abstinent from smoking for 2 days after starting a quit attempt (probability = .50 vs. .64; P value = .012). Young adults aged 18 or above were more likely to relapse into smoking (adjusted HR = 1.50, 95% CI = 1.01, 2.22). CONCLUSIONS: Depressive symptoms may delay young smokers from initiating quit attempts and shorten their abstinence. A baseline screening process is suggested for identifying youths with co-occurring depressive disorder and nicotine dependence. Further studies should examine a collaborative model of smoking cessation that involves both counselors and physicians in preventing young smokers from rapid relapses after they make quit attempts.

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.

Milk consumption in relation to incidence of nasopharyngeal carcinoma in 48 countries/regions.

BACKGROUND: Decreasing trends of nasopharyngeal carcinoma (NPC) incidence have been consistently reported in endemic populations but the etiology of NPC remains unclear. The objective of our study was to assess the international and local (Hong Kong) correlations of milk and dairy products per capita consumption with NPC incidence. METHODS: We conducted an ecological study in 48 countries/regions. Age standardized incidence rates of NPC were obtained from the Cancer Incidence in Five Continents. Dairy product consumption and Human Development Index were obtained from the Food and Agriculture Organization of the United Nations and the United Nations Development Programme. Spearman correlation, multivariate analysis and time-lagged analysis were performed. RESULTS: The negative correlations between milk consumption and decreased age standardized incidence rates of NPC were observed in the 48 countries/regions adjusting for Human Development Index in endemic countries/regions. In Hong Kong, multivariate analysis, after adjusting for other potential confounders, including salted fish, cigarette, vegetable consumption and socioeconomic status, showed consistently negative and significant correlations between milk consumption and NPC incidence (The strongest coefficient (ß) was observed at 10-year lag in males [ß = -0.439; P < 0.01] and in females [ß = -0.258; P < 0.01]). CONCLUSIONS: Our study showed the correlations on milk consumption per capita and against lower risk of NPC in 48 countries/regions and in Hong Kong. These hypothesis-generating results could support further studies on individual exposures and the disease.

A block randomized controlled trial of a brief smoking cessation counselling and advice through short message service on participants who joined the Quit to Win Contest in Hong Kong.

The present trial examined the effectiveness of brief interventions for smokers who joined the Hong Kong Quit to Win Contest to quit smoking. A block randomized controlled trial allocated 1003 adult daily smokers to three groups: (i) The TEL group (n = 338) received a 5-min nurse-led telephone counselling; (ii) The SMS group (n = 335) received eight text messages through mobile phone and (iii) The CONTROL group (n = 330) did not receive the above interventions. Participants with biochemically verified abstinence at 6-month follow-up could receive cash incentive. The primary outcome was the self-reported 7-day point prevalence (PP) of tobacco abstinence at 6-month follow-up. The abstinence rate in the TEL, SMS and CONTROL group was 22.2, 20.6 and 20.3%, respectively (P for TEL versus CONTROL = 0.32; P for SMS versus CONTROL = 0.40). When abstinence at 2-, 6- and 12-month follow-up was modelled simultaneously, the TEL group had a higher abstinence than the CONTROL group (Adjusted OR = 1.38, 95% CI = 1.01-1.88, P = 0 .04). In the Quit to Win Contest, the brief telephone counselling might have increased abstinence, but the text messages had no significant effect. Further studies on intensive intervention and interactive messaging services are warranted.

Using WhatsApp and Facebook Online Social Groups for Smoking Relapse Prevention for Recent Quitters: A Pilot Pragmatic Cluster Randomized Controlled Trial.

BACKGROUND: Quit attempters often have episodes of smoking relapse before they eventually quit. Interactive text messaging through mobile phones has been shown to increase abstinence. This service can be potentially applied on the platform of a social networking service to help quitters maintain abstinence. OBJECTIVE: Our aim was to determine if the group discussion and reminders via the WhatsApp or Facebook social group were effective to prevent smoking relapse in quitters who had stopped smoking recently. METHODS: This was a single-blinded, parallel, 3-arm pilot cluster randomized controlled trial allocating recent quitters, who had completed an 8-week treatment and reported abstinence for at least 7 days, to WhatsApp (n=42), Facebook (n=40), and a control group (n=54). The 2 intervention groups participated in a 2-month online group discussion with either WhatsApp or Facebook moderated by a trained smoking cessation counselor and received a self-help booklet on smoking cessation. The control group only received the booklet. The primary outcome was the 2- and 6-month relapse rates, defined as the proportion of participants who smoked at least 5 cigarettes in 3 consecutive days. RESULTS: Fewer participants in the WhatsApp group (17%, 7/42) reported relapse than the control group (42.6%, 23/54) at 2-month (OR 0.27, 95% CI 0.10-0.71) and 6-month (40.5%, 17/42 vs 61.1%, 33/54; OR 0.43, 95% CI 0.19-0.99) follow-ups. The Facebook group (30.0%, 12/40) had an insignificantly lower relapse rate than the control group (42.6%, 23/54) at 2-month (OR 0.58, 95% CI 0.24-1.37) and 6-month (52.5%, 13/40 vs 61.1%, 33/54; OR 0.70, 95% CI 0.31-1.61) follow-ups. The WhatsApp social groups had more moderators' posts (median 60, IQR 25 vs median 32, IQR 7; P=.05) and participants' posts (median 35, IQR 50 vs median 6, IQR 9; P=.07) than their Facebook counterparts, but the difference was insignificant. CONCLUSIONS: The intervention via the WhatsApp social group was effective in reducing relapse probably because of enhanced discussion and social support. Inactive discussion in the Facebook social group might have attributed to the lower effectiveness. CLINICALTRIAL: Clinicaltrials.gov NCT02007369; https://clinicaltrials.gov/show/NCT02007369 (Archived by WebCite® at http://www.webcitation.org/6c3RbltQG).

Gamified Strength Recognition and Quiz to Enhance COVID-19 Prevention, Knowledge, Behaviors, and Family Well-Being.

Background: Promoting COVID-19 prevention is key to pandemic control and innovative interventions can help communicate reliable science to the public. Under the Hong Kong Jockey Club SMART Family-Link Project, we developed and evaluated a pilot intervention for promoting COVID-19 prevention through a web-based family game, guided by the Theory of Planned Behavior and a strength-based approach. Methods: The "SMART Epidemic prevention" pilot theme was launched to the public on September 21, 2020 for 4 weeks. The game had two parts: (i) strength recognition and (ii) quiz questions on knowledge and behaviors about COVID-19 prevention. Simple baseline, in-game, and postgame evaluation assessed players' perceived knowledge, behaviors, family well-being, game satisfaction, and perceived benefits. Results: Of 86 registered families, 55 played actively, including 212 players (51% female, 35% aged below 18) who self-identified as children (44%), parents (39%), and grandparents (11%). In weeks 1 and 4, an average of 7 and 18 game rounds were played per family, and 86.6% and 75.9% of rounds had perfect (2) behavior matches. Postgame evaluation with 51 families showed improvements in epidemic prevention knowledge and behaviors, family communication, family happiness (all P < 0.001), and family relationship (P = 0.002) with small effect sizes (0.15-0.29). Overall game satisfaction was rated 4.49 (scale of 1-5). Ninety-four percent of families shared knowledge from the game with others. Conclusions: Our pilot web-based family game first showed preliminary evidence on enhancing COVID-19 prevention knowledge and behaviors, and family well-being, with participants recognizing family strengths, reporting high satisfaction and various perceived benefits, and showing sustained gameplay. Trial Registration: The research protocol was registered at the National Institutes of Health (Identifier No. NCT04550065) on September 16, 2020.