Relationship between esophageal squamous cell carcinoma risk and alcohol-related ALDH2 and ADH1B polymorphisms: Evidence from a meta-analysis and Mendelian randomization analysis.

BACKGROUND: Previous studies have shown that ALDH2 and ADH1B genes may be associated with alcohol metabolism and the risk of esophageal squamous cell carcinoma (ESCC), with inconsistent results. This meta-analysis aimed at comprehensively assessing the associations between ALDH2 and ADH1B polymorphisms and the risk of ESCC to synthesize and clarify the evidence. METHODS: We calculated summary estimates of the associations between four genetic variants (rs671 and rs674 in ALDH2, and rs1229984 and rs1042026 in ADH1B) and the ESCC risk across 23 publications in the additive model and allelic model. Venice criteria, Bayesian false discovery probability (BFDP), and false-positive reporting probability (FPRP) were used to assess the strength of epidemiological evidence. Heterogeneity among studies was evaluated by using the Higgin's I2 statistic, and publication bias was assessed by using funnel plots and Begg's test. A Mendelian randomization (MR) analysis was performed to determine the causal association between alcohol intake and esophageal cancer risk. Data from the HaploReg v4.1 and PolyPhen-2 were analyzed for functional annotations. RESULTS: Of the four genetic variants, rs671 of ALDH2 was associated with a significantly reduced risk of ESCC (OR: 0.60, 95% CI: 0.50-0.73), whereas rs1229984 of ADH1B was associated with a significantly increased risk (2.50, 95% CI: 1.70-3.69) in the additive model. In the allelic model, the variant rs1229984 of ADH1B also increased the risk of ESCC (OR: 1.50; 95% CI: 1.21-1.87). The result for the variant rs671 was considered as strong epidemiological evidence. Functional annotations identified that the four variants were related to the enhancer histone marks and motif changes. The other two variants were not associated with the ESCC risk (rs674 of ALDH2 OR: 1.22, 95% CI: 0.71-2.12; rs1042026 of ADH1B OR: 1.28, 95% CI: 0.52-3.14) in the additive model. The MR analysis did not find a causal effect of alcohol on the esophageal cancer risk. CONCLUSIONS: The results showed that ADH1B rs1229984 was significantly associated with an increased the risk of ESCC.

Global, Regional, and National Burden of Cancer in Children Younger Than 5 Years, 1990-2019: Analysis of the Global Burden of Disease Study 2019.

Objectives: To quantify the burden and variation trends of cancers in children under 5 years at the global, regional, and national levels from 1990 to 2019. Methods: Epidemiological data for children under 5 years who were diagnosed with any one childhood cancer were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) from 1990 to 2019. The outcomes were the absolute numbers and rates of incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for different types of cancer. Results: In 2019, 8,774,979.1 incident cases (95% uncertainty interval [UI]: 6,243,599.2 to11,737,568.5) and 8,956,583.8 (6,446,323.9 to 12,364,520.8) prevalent cases of cancer in children under 5 years were identified worldwide; these cancers resulted in 44,451.6 (36,198.7 to 53,905.9) deaths and 3,918,014.8 (3,196,454.9 to 4,751,304.2) DALYs. From 1990 to 2019, although the numbers of incident and prevalent cases only decreased by -4.6% (-7.0 to -2.2) and -8.3% (-12.6 to -3.4), respectively, the numbers of deaths and DALYs clearly declined by -47.8% (-60.7 to -26.4) and -47.7% (-60.7 to -26.2), respectively. In 2019, the middle sociodemographic index (SDI) regions had the highest incidence and prevalence, whereas the low SDI regions had the most mortality and DALYs. Although all of the SDI regions displayed a steady drop in deaths and DALYs between 1990 and 2019, the low-middle and low SDI regions showed increasing trends of incidence and prevalence. Leukemia remained the most common cancer globally in 2019. From 1990 to 2019, the burdens of leukemia, liver cancer, and Hodgkin's lymphoma declined, whereas the incidence and prevalence of other cancers grew, particularly testicular cancer. Conclusions: The global childhood cancer burden in young children has been steadily decreasing over the past three decades. However, the burdens and other characteristics have varied across different regions and types of cancers. This highlights the need to reorient current treatment strategies and establish effective prevention methods to reduce the global burden of childhood cancer.

Online social networking addiction and depression: The results from a large-scale prospective cohort study in Chinese adolescents.

BACKGROUND AND AIMS: The aim of this study is to estimate the longitudinal associations between online social networking addiction (OSNA) and depression, whether OSNA predicts development of depression, and reversely, whether depression predicts development of OSNA. METHODS: A total of 5,365 students from nine secondary schools in Guangzhou, Southern China were surveyed at baseline in March 2014, and followed up 9 months later. Level of OSNA and depression were measured using the validated OSNA scale and CES-D, respectively. Multilevel logistic regression models were applied to estimate the longitudinal associations between OSNA and depression. RESULTS: Adolescents who were depressed but free of OSNA at baseline had 1.48 times more likely to develop OSNA at follow-up compared with those non-depressed at baseline [adjusted OR (AOR): 1.48, 95% confidence interval (CI): 1.14-1.93]. In addition, compared with those who were not depressed during the follow-up period, adolescents who were persistently depressed or emerging depressed during the follow-up period had increased risk of developing OSNA at follow-up (AOR: 3.45, 95% CI: 2.51-4.75 for persistent depression; AOR: 4.47, 95% CI: 3.33-5.99 for emerging depression). Reversely, among those without depression at baseline, adolescents who were classified as persistent OSNA or emerging OSNA had higher risk of developing depression compared with those who were no OSNA (AOR: 1.65, 95% CI: 1.01-2.69 for persistent OSNA; AOR: 4.29; 95% CI: 3.17-5.81 for emerging OSNA). CONCLUSION: The findings indicate a bidirectional association between OSNA and depression, meaning that addictive online social networking use is accompanied by increased level of depressive symptoms.

Insomnia partially mediated the association between problematic Internet use and depression among secondary school students in China.

Background and aims This study aims to examine the mediating effects of insomnia on the associations between problematic Internet use, including Internet addiction (IA) and online social networking addiction (OSNA), and depression among adolescents. Methods A total of 1,015 secondary school students from Guangzhou in China participated in a cross-sectional survey. Levels of depression, insomnia, IA, and OSNA were assessed using the Center for Epidemiological Studies-Depression Scale, Pittsburgh Sleep Quality Index, Young's Diagnostic Questionnaire, and Online Social Networking Addiction Scale, respectively. Logistic regression models were fit to test the associations between IA, OSNA, insomnia, and depression. The mediation effects of insomnia were tested using Baron and Kenny's strategy. Results The prevalence of depression at moderate level or above (CES-D ≥ 21), insomnia, IA, and OSNA were 23.5%, 37.2%, 8.1%, and 25.5%, respectively. IA and OSNA were significantly associated with depression (IA: AOR = 2.79, 95% CI: 1.71, 4.55; OSNA: AOR = 3.27, 95% CI: 2.33, 4.59) and insomnia (IA: AOR = 2.83, 95% CI: 1.72, 4.65; OSNA: AOR = 2.19, 95% CI: 1.61, 2.96), after adjusting for significant background factors. Furthermore, insomnia partially mediated 60.6% of the effect of IA on depression (Sobel Z = 3.562, p < .002) and 44.8% of the effect of OSNA on depression (Sobel Z = 3.919, p < .001), respectively. Discussion The high prevalence of IA and OSNA may be associated with increased risk of developing depression among adolescents, both through direct and indirect effects (via insomnia). Findings from this study indicated that it may be effective to develop and implement interventions that jointly consider the problematic Internet use, insomnia, and depression.

Randomised controlled trial of effect of whole soy replacement diet on features of metabolic syndrome in postmenopausal women: study protocol.

INTRODUCTION: Metabolic syndrome (MetS) is a public health problem in postmenopausal women. Whole soy foods are rich in unsaturated fats, high quality plant protein and various bioactive phytochemicals that may have a beneficial role in the management of MetS. The aim of the study is to examine the effect of whole soy replacement diet on the features of MetS among postmenopausal women. METHODS AND ANALYSIS: This will be a 12-month, randomised, single-blind, parallel controlled trial among 208 postmenopausal women at risk of MetS or with early MetS. After 4 weeks' run-in, subjects will be randomly allocated to one of two intervention groups, whole soy replacement group or control group, each for 12 months. Subjects in the whole soy group will be required to include four servings of whole soy foods (containing 25 g soy protein) into their daily diet iso-calorically, replacing red or processed meat and high fat dairy products. Subjects in the control group will remain on a usual diet. The outcome measures will include metabolic parameters as well as a 10-year risk for ischaemic cardiovascular disease. We hypothesise that the whole soy substitution diet will notably improve features of MetS in postmenopausal women at risk of MetS or with early MetS. The study will have both theoretical and practical significance. If proven effective, the application of the whole soy replacement diet model will be a safe, practical and economical strategy for MetS prevention and treatment. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Ethics Committee of the Chinese University of Hong Kong. The results will be disseminated via conference presentations and papers in academic peer reviewed journals. Data files will be deposited in an accessible repository. TRIAL REGISTRATION NUMBER: NCT02610322.

Genetic variants in EBV reactivation-related genes and the risk and survival of breast cancer.

Tumor susceptibility gene 101 (TSG101) and activating transcription factor 2 (ATF2) have been suggested to involve in the reactivation of EBV which has implications in the development and progression of breast cancer. Therefore, the polymorphisms of TSG101 and ATF2 may associate with breast cancer risk and prognosis. A case-control study with 1551 breast cancer cases and 1605 age-matched controls were conducted in Guangzhou, China. We have also successfully followed up 1168 cases until December 31, 2014. The variant allele of TSG101 rs2292179 was associated with a non-significant reduced risk of breast cancer, particularly among women with BMI < 24 (kg/m(2)) (P for interaction <0.05). For ATF2 rs3845744, the variant allele was also associated with a significantly reduced breast cancer risk [odds ratio (OR) (95 % confidence interval (CI)) 0.86 (0.74∼1.00)], and the association occurred among only postmenopausal women [OR (95 % CI) 0.69 (0.54∼0.88)] (P for interaction <0.05). Breast cancer risk was further reduced with the increasing numbers of the variant G alleles of the two polymorphisms (P for trend <0.05). We did not find an overall association of the two loci with breast cancer prognosis, while the hazard ratios of the two loci (AG/GG vs. AA) were significantly higher among postmenopausal women than premenopausal women (P = 0.046, 0.016 for TSG101 rs2292179 and ATF2 rs3845744, respectively). In summary, the variant alleles of TSG101 rs2292179 and ATF2 rs3845744 were associated with a reduced risk of breast cancer, particularly for subjects with BMI <24 (kg/m(2)) and postmenopausal women, respectively. The two SNPs and menopausal status may have a significant interaction on breast cancer progression.

Night-shift work, sleep duration, daytime napping, and breast cancer risk.

OBJECTIVES: Sleep habits vary among different countries, and sleep problems may cause various health problems. The aim of our study was to evaluate the separate and combined associations of night-shift work, sleep duration, and daytime napping with breast cancer risk among the Chinese population. METHODS: This study conducted face-to-face interviews with 712 women diagnosed with incident invasive breast cancer before treatment and 742 age-matched controls. Information on sleep habits, demographic characteristics, and suspected or established risk factors of breast cancer were collected from the two groups. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Night-shift work was associated with an increased risk of breast cancer [OR (95% CI): 1.34 (1.05-1.72)]. Compared to women with a sleep duration of 6.1-8.9 h/day, women who had shorter [(≤6.0 h/day) (OR (95% CI): 1.53 (1.10-2.12)] and longer (≥9.0 h/day) sleep duration [(OR (95% CI): 1.59 (1.17-2.17)] had an increased risk of breast cancer. In addition, daytime napping was associated with a reduced risk of breast cancer among night-shift workers [OR (95% CI): 0.57 (0.36-0.90)], but no association was found among women who never had night-shift work [OR (95% CI): 1.01 (0.75-1.35)] (P for interaction = 0.054). Night-shift work and longer sleep duration also synergistically increased breast cancer risk [OR (95% CI): 3.69 (1.94-7.02)] (P for interaction = 0.009). CONCLUSIONS: Sleep problems, including night-shift work, and shorter and longer sleep duration, are associated with an increased breast cancer risk. In particular, the combined effects of night-shift work with no daytime napping or longer sleep duration are greater than the independent effects.