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

Background:   Several molecular markers have important roles in glioma management. Mutations in the isocitrate dehydrogenase ( IDH ) gene are associated with the grading and prognosis of glioma. Methylation in the promoter region of the O (6)-methylguanine-DNA methyltransferase ( MGMT ) gene is an important determinant of glioma sensitivity to alkylating agents. Studies in various cancers indicated that IDH1 mutations and MGMT promoter methylations were associated with smoking habits. However, these associations in gliomas are still unclear. Accordingly, this study aimed to examine the association among smoking, IDH1 mutations, MGMT promoter methylation, and grading in glioma patients.  Methods:   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 IDH1 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.  Results:   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%, p=0.01). Among 122 patients, 24 (19.7%) of them carried IDH1 mutation. Smoking patients have a significantly higher proportion of IDH1 mutation compared with non-smokers (31.4% vs. 14.9%, p<0.001). No significant association was found between intensity and duration of smoking with IDH1 mutations and glioma grading. No significant association was found between smoking and MGMT promoter methylation.   Conclusions:   In glioma patients, smoking is associated with IDH1 mutations and grading but not with MGMT promoter methylation.