Associations among smoking, IDH mutations ,MGMT promoter methylation, and grading in glioma a cross-sectional study

<b>Methods</b><br>Patients were recruited from Dr. Sardjito General Hospital (a referral hospital in Yogyakarta and Central Java region) and its network hospitals. Genomic DNA was extracted from formalin-fixed paraffin-embedded samples or fresh glioma tissues. Identification of <i>IDH1</i> mutation was performed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) or DNA sequencing. Methylation-specific real-time PCR was performed to identify MGMT promoter methylation status. Smoking status was obtained by history taken from the patient or family members.<b>Results</b>In total, 122 patients were included in this study. As many as 35 patients (28.7%) had a smoking history. Most smokers (57.1%) smoke less than ten cigarettes per day. However, most of them (68.8%) have been smoking for more than 20 years. Smoking patients have a significantly higher proportion of high-grade glioma than non-smokers (80% vs. 55.2%, <i>p</i>=0.01). Among 122 patients, 24 (19.7%) of them carried <i>IDH1</i> mutation. Smoking patients have a significantly higher proportion of <i>IDH1</i> mutation compared with non-smokers (31.4% vs. 14.9%, <i>p</i>&lt;0.001). No significant association was found between intensity and duration of smoking with <i>IDH1</i> mutations and glioma grading. No significant association was found between smoking and MGMT promoter methylation.<b>Conclusions</b>In glioma patients, smoking is associated with <i>IDH1</i> mutations and grading but not with MGMT promoter methylation.<b>方法</b><br>研究对象招募自萨尔德吉托综合医院（日惹和中爪哇地区的转诊医院）及其联网医院。从福尔马林固定石蜡包埋样本或新鲜胶质瘤组织中提取基因组DNA。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）或DNA测序鉴定<i>异柠檬酸脱氢酶1（IDH1）</i>突变。采用甲基化特异性实时荧光定量PCR检测O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化状态。吸烟史通过问询患者或家属获取。<b>结果</b><br>本研究共纳入122例患者。其中35例（28.7%）存在吸烟史。多数吸烟者（57.1%）每日吸烟量少于10支，但其中68.8%的吸烟者吸烟时长超过20年。吸烟患者的高级别胶质瘤占比显著高于非吸烟患者（80% vs. 55.2%，<i>p</i>=0.01）。122例患者中，24例（19.7%）携带<i>IDH1</i>突变。吸烟患者的<i>IDH1</i>突变占比显著高于非吸烟患者（31.4% vs. 14.9%，<i>p</i>&lt;0.001）。未发现吸烟强度与吸烟时长与<i>IDH1</i>突变及胶质瘤分级存在显著关联。未发现吸烟与MGMT启动子甲基化存在显著关联。<b>结论</b>在胶质瘤患者中，吸烟与<i>IDH1</i>突变及胶质瘤分级相关，但与MGMT启动子甲基化无关联。