Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Effects of Palliative Care for Progressive Neurologic Diseases: A Systematic Review and Meta-Analysis.

OBJECTIVES: To determine the association of palliative care for progressive neurologic diseases with patient- and caregiver-centered outcomes. DESIGN: Systematic review and meta-analysis of randomized controlled trials and quasi-experimental studies, including pilot studies. SETTING AND PARTICIPANTS: Adults with progressive neurologic diseases (dementia, multiple sclerosis, Parkinson's disease, motor neuron disease, multiple system atrophy, and progressive supranuclear palsy) and their caregivers. METHODS: MEDLINE, EMBASE, CINAHL PLUS, Cochrane CENTRAL, and PubMed were searched from inception to September 2021. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane risk of bias tools. Narrative synthesis was conducted. Patient quality of life (QoL), symptom burden, caregiver burden, and satisfaction with care were meta-analyzed using a random-effects model. RESULTS: Fifteen trials provided data on 3431 patients (mean age, 73.9 years). Compared with usual care, palliative care was statistically significantly associated with lower symptom burden [standardized mean difference (SMD), -0.34 (95% Cl, -0.59 to -0.09)] and higher caregiver satisfaction [SMD, 0.41 (95% Cl, 0.12 to 0.71)] and patient satisfaction [SMD, 0.43 (95% Cl, -0.01 to 0.87)]. However, the associations were not significant after excluding studies with high risk of bias. Insignificant associations of palliative care with caregiver burden [SMD, -0.09 (95% Cl, -0.21 to 0.03)] and patient QoL [SMD, 0.19 (95% Cl, -0.07 to 0.44)] were observed. CONCLUSIONS AND IMPLICATIONS: Palliative care is likely to improve symptom burden and satisfaction with care among patients with progressive neurologic diseases and their caregivers, while its effects on QoL and caregiver burden remains inconclusive. Specific intervention components including interdisciplinary team, palliative care physicians, home visits, and spiritual care appeared to be associated with increased effects on improving palliative outcomes. More rigorous designed studies are warranted to examine the effects of neuropalliative care, effective intervention components, optimal timing, and symptom triggers of palliative care referrals

Interobserver reliability in the endoscopic diagnosis and grading of Barrett's esophagus: An Asian multinational study

10.1055/s-0030-1255629Endoscopy429699-704ENDC

Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women

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

Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women

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