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We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (p = 0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (OR = 1.31, 95% CI: 1.03, 1.66, p = 0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.

Hyperglycemia with high hemoglobin A1c (HbA1c) levels is associated with significant health risks. However, the relationship between HbA1c levels and the physical functioning status in later life remains uncertain and so is the possible underlying mechanism.We conducted a prospective study of 2,565 initially well-functioning community-dwelling older adult aged 55 years and older from the Healthy Aging Longitudinal Study in Taiwan. Each participant received baseline measurements of blood HbA1c and inflammatory markers levels and repeated assessments of physical functioning over a mean follow-up period of 5.3 years. We used generalized linear mixed-effects regression to estimate the adjusted changes in the odds ratio for self-reported physical functioning impairment and Short Physical Performance Battery (SPPB) score according to baseline HbA1c levels (categorized into 0.5% increments from5.5% to ≥7.0%).HbA1c levels showed a U-shaped relationship with changes in the odds ratio for physical functioning impairment and SPPB score (p for quadratic term.001). Compared with participants with an HbA1c of 5.5% to6.0%, those with an HbA1c of5.5% or ≥7.0% had a higher annual increase in the odds ratio for physical functioning impairment (odds ratio [95% confidence interval] per year, 1.25 [1.04-1.50] and 1.21 [1.04-1.41]) and a higher annualized decrease in SPPB score (coefficient [95% confidence interval], -0.05 [-0.10 to 0.00] and -0.04 [-0.08 to 0.00]). These relationships were nonlinear only in participants with high soluble interleukin-6 receptor levels (48,124 pg/mL; p for interaction.05).High and low HbA1c levels at baseline are associated with faster physical functioning decline, particularly among individuals with elevated circulating soluble interleukin-6 receptor, a sign of enhanced interleukin-6 trans-signaling.

Objective To describe psychotropic medications prescription patterns among adolescents in Taiwan; focusing on age, gender, duration of treatments and various classes of psychotropic medications. Design A retrospective description analysis. Setting Taiwan National Health Insurance Database. Participants Twelve to seventeen years' patients treated with psychotropic medications. Intervention None. Main Outcome Measure(s) Percentage and duration of treatment with psychotropic medications during the study periods by medication classes and age groups were calculated. In addition, top three prescribed psychotropic medications were also determined. Results A total of 3,120 patients were prescribed psychotropic drugs. The percentage of adolescent patients that received anxiolytics and antidepressants in 2002-2012 were 2.89% and 2.15%, respectively. Also, 851 patients (1.21%) were prescribed hypnotics and 638 (0.91%) were given sedatives. The prevalence rate of the prescription of psychotropic drugs increased steadily with age and females were more treated than males except antipsychotic. Among psychotropic drugs, antidepressants (mean: 8.6 times) were refilled more but antipsychotics (mean 188 days) were the long-term treatment drugs. Additionally, the trend of hospital visits fluctuated over the year while May and December showed a higher rate of visits. Conclusions These findings show that the prevalence of psychotropic drug prescriptions in Taiwanese adolescents is even low but increasing trends in the prescription of these medications raises some concern. As the evidence of psychotropic drug safety and effectiveness in adolescents is still inadequate; we recommend that healthcare providers should consider psychotropic drugs therapy, continuously monitor for outcomes and empower their patients to improve their knowledge, therapeutic outcomes and quality of life.

C-reactive protein (CRP) encoded by CRP gene is a reflection of systemic inflammation. Many studies associated CRP level with diabetes and glucose levels, but the association of CRP gene with these traits is unclear. We conducted a cross-sectional study consisting of 945 siblings from 330 families collected by the Stanford Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe) to investigate associations between CRP polymorphisms, circulating CRP, diabetes, and glucose levels. Five single-nucleotide polymorphisms were analyzed: rs3093059, rs2794521, rs1417938, rs1800947, and rs1205. The generalized estimating equation approach was used to deal with correlated data within families. CRP level was positively correlated with diabetes prevalence and levels of fasting and 2-hour glucose (each P C at rs3093059 and G at rs1205 were associated with elevated CRP level (each P −6). Allele C at rs3093059 was associated with fasting glucose (β = 0.20, P = 0.045) and G at rs1205 was associated with 2-hour glucose (β = 0.46, P = 0.00090) post oral glucose tolerance test, but only the latter passed Bonferroni correction. No polymorphism was associated with diabetes. Since 2-hour glucose is an indicator of glucose tolerance, this study indicated CRP gene is associated with glucose intolerance.

Patients with non-small cell lung cancer (NSCLC) with mutated epidermal growth factor receptor (EGFR) are relatively sensitive to EGFR-tyrosine kinase inhibitor (TKI) treatment and have longer progression-free survival (PFS) when treated with EGFR-TKI compared with platinum-based chemotherapy. However, many patients with advanced NSCLC who have mutated EGFR do not respond to first-line EGFR-TKI treatment and still have shorter PFS.The aim of this study was to identify genetic variants associated with PFS among patients with lung adenocarcinoma who were treated with first-line EGFR-TKIs.A genome-wide association study on PFS was performed in never-smoking women diagnosed with lung adenocarcinoma and who were treated with first-line EGFR-TKIs (n = 128). Significant single-nucleotide polymorphisms (SNPs) were selected for follow-up association analysis (n = 198) and for replication assay in another independent cohort (n = 153).We identified SNPs at 4q12 associated with PFS at genome-wide significance (P 10Genetic variants in 4q12 merit further investigation to assess their potential as pharmacogenomic predictors for and to understand the biology underlying its influence on PFS in patients treated with TKI therapy.

Human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) plays an important role in repairing oxidative DNA damage induced by tobacco carcinogens. In this case-control study, the authors examined the interactive effect of hOGG1 gene polymorphisms and cigarette smoking on the risk of lung cancer in Taiwan. A total of 1,096 cases and 1,007 controls were enrolled from 6 medical centers in Taiwan during 2002-2004. hOGG1 Ser326Cys genetic polymorphisms were determined using the MassARRAY system (SEQUENOM, Inc., San Diego, California). Tobacco smoking history was obtained through personal interview according to a structured questionnaire. Logistic regression analysis was used to estimate multivariate-adjusted odds ratios and 95% confidence intervals. The odds of developing lung cancer for persons with the Cys/Cys genotype versus the Ser/Ser genotype were 1.11 (95% confidence interval (CI): 0.74, 1.65) for never smokers, 1.45 (95% CI: 0.74, 2.83) for moderate smokers, and 3.52 (95% CI: 1.54, 8.06) for heavy smokers. The P value for interaction in the logistic model was 0.01. The increased risk associated with the Cys/Cys genotype among heavy smokers remained statistically significant for various histologic types of lung cancer, including adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. The authors conclude that there was a noticeable modifying effect on the association between hOGG1 genotype and lung cancer risk by cigarette smoking status.