Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma

Lung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East Asians (30-50%) than in European/Americans (10-20%). Here we investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA class II at 6p21.32 (rs2179920; P =5.1 × 10(-17), per-allele OR=1.36) and 6p21.1 (FOXP4) (rs2495239; P=3.9 × 10(-9), per-allele OR=1.19) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma. This study indicates that multiple genetic factors underlie the risk of lung adenocarcinomas with EGFR mutations

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

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 (P interaction  = 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

Autoimmune alopecia areata due to thymoma without myasthenia gravis: a case report

Abstract Background Thymoma is associated with autoimmune diseases. Myasthenia gravis is frequently associated with thymoma, but cases of thymoma complicated by alopecia areata are very rare. In this report, we present a case of thymoma associated with alopecia areata, but without Myasthenia gravis. Case presentation A 60-year-old woman had a complaint of rapid progression of alopecia areata. A hair follicular biopsy was performed, which showed the infiltration of CD8-positive lymphocytes. She was prescribed topical steroids for 2 months prior to surgery, but her hair loss was not improved. Screening computed tomography showed a mass in the anterior mediastinum, which was suspected to be a thymoma. Myasthenia gravis was ruled out because she had no relevant symptoms or physical findings, and no anti-acetylcholine receptor antibodies were detected in serum. We performed a transsternal extended thymectomy based on a diagnosis of thymoma Masaoka stage I, without myasthenia gravis. Pathological examination showed Type AB thymoma, Masaoka stage II. The chest drainage tube was removed on postoperative day 1, and the patient was discharged on postoperative day 6. The patient has continued topical steroids and showed improvement 2 months postoperatively. Conclusions Although alopecia areata is a rare complication in thymoma cases without myasthenia gravis, thoracic surgeons need to keep this condition in mind because alopecia reduces the patient's quality of life