Lung Cancer Risk in Never-Smokers of European Descent is Associated With Genetic Variation in the 5(p)15.33 TERT-CLPTM1Ll Region

Introduction: Inherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer. Methods: We conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer. Results: We detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722-0.820; p value 5.31 x 10(-16)), rs380286 (OR: 0.770, 95% CI: 0.723-0.820; p value 4.32 x 10(-16)), and rs4975616 OR: 0.778, 95% CI: 0.730-0.829; p value 1.04 x 10(-14)). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate. Conclusions: We found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer

Profil penggunaan insulin intermediate acting pada pasien diabetes melitus tipe 2 di RSUD Kabupaten Sidoarjo

Diabetes melitus (DM) merupakan suatu penyakit metabolik yang ditandai dengan hiperglikemia atau peningkatan kadar gula darah yang kronis dan bervariasi, akibat kelainan sekresi insulin, kerja insulin atau keduanya. Diabetes melitus tipe 2 disebabkan kegagalan relatifsel beta dan resistensi insulin.Resistensi insulin adalah turunnya kemampuan insulin untuk merangsang pengambilan glukosa oleh jaringan perifer dan untuk menghambat produksi glukosa oleh hati. Pemberian terapi insulin bertujuan untuk mengontrol kadar glukosa darah yang lebih baik pada pasien diabetes melitus tipe 2. Untuk mengetahui profil penggunaan insulin intermediate acting pada pasien DM meliputi jenis insulin, dosis, lama pemberian, data laboratorium dan data klinik. Penelitian observasional berupa studi retrospektif pada pasien diabetes melitus tipe 2 periode Januari 2017-Mei 2018.Terdapat 10 sampel pasien yang menerima terapi insulin intermediate acting dan kombinasi insulin intermediate acting dari 100 pasien yang terdiagnosa diabetes melitus tipe 2 dan penggunaan terapi insulin tunggal intermediate acting sebesar 58% dan penggunaan kombinasi insulin intermediate acting dengan kerja panjang maupun OAD sebesar 42%. Penggunaan insulin dengan penggantian jenis insulin dan dosis insulin sebanyak 50%. Rute pemberian paling banyak yaitu melalui subkutan

Profil penggunaan insulin intermediate acting pada pasien diabetes melitus tipe 2 di RSUD Kabupaten Sidoarjo

Diabetes melitus (DM) merupakan suatu penyakit metabolik yang ditandai dengan hiperglikemia atau peningkatan kadar gula darah yang kronis dan bervariasi, akibat kelainan sekresi insulin, kerja insulin atau keduanya. Diabetes melitus tipe 2 disebabkan kegagalan relatifsel beta dan resistensi insulin.Resistensi insulin adalah turunnya kemampuan insulin untuk merangsang pengambilan glukosa oleh jaringan perifer dan untuk menghambat produksi glukosa oleh hati. Pemberian terapi insulin bertujuan untuk mengontrol kadar glukosa darah yang lebih baik pada pasien diabetes melitus tipe 2. Untuk mengetahui profil penggunaan insulin intermediate acting pada pasien DM meliputi jenis insulin, dosis, lama pemberian, data laboratorium dan data klinik. Penelitian observasional berupa studi retrospektif pada pasien diabetes melitus tipe 2 periode Januari 2017-Mei 2018.Terdapat 10 sampel pasien yang menerima terapi insulin intermediate acting dan kombinasi insulin intermediate acting dari 100 pasien yang terdiagnosa diabetes melitus tipe 2 dan penggunaan terapi insulin tunggal intermediate acting sebesar 58% dan penggunaan kombinasi insulin intermediate acting dengan kerja panjang maupun OAD sebesar 42%. Penggunaan insulin dengan penggantian jenis insulin dan dosis insulin sebanyak 50%. Rute pemberian paling banyak yaitu melalui subkutan