Smoking-related Genomic Alterations Are Observed in Patients with Glioma and May Contribute to Shortened Survival
Julia Landry1, Gabriella Bognet1, Sarah Ahr2, Shakti Ramkissoon3, Michael Chan4, Christina Cramer4, Stephen Tatter5, Adrian Laxton5, Jaclyn White5, Ryan Mott3, Kimberly Stogner-Underwood3, Eric Severson6, Zachary Wallen6, Fang-Chi Hsu7, Glenn Lesser8, Roy Strowd9
1Wake Forest University, 2Thomas Jefferson University, 3Department of Pathology, 4Department of Radiation Oncology, 5Department of Neurosurgery, 6LabCorp Oncology, 7Department of Public Health Sciences, 8Department of Internal Medicine, 9Department of Neurology, Wake Forest University School of Medicine
Objective:
To evaluate associations between smoking status, genetic alterations in primary glial neoplasms, and impact on survival.
Background:
Cigarette smoking may contribute to cancer-associated genomic instability with increased tumor mutation burden and frequency of KRAS, TP53, and other alterations. Few studies have explored smoking-associated genomic instability in patients with primary glioma.
Design/Methods:
Retrospective analysis was performed of adults (≥18 years) diagnosed with glioma (i.e., glioblastoma, astrocytoma, oligodendroglioma; WHO Grade 1–4) between 2000-2023, receiving primary oncologic care at Wake Forest Baptist Comprehensive Cancer Center, and available data on smoking status. Data was queried for demographic, clinical, molecular, and treatment characteristics. Smoking status was defined as active/former vs never smoker. P-value <0.05 defined as significant and <0.25 after multiple testing correction.
Results:
721 patients were identified; mean age 54.9±16 years at diagnosis and 58.2±14.3 at death or follow-up; 57% male; 58% GBM, 23% astrocytoma, 16% oligodendroglioma, 3% other glioma by 2016 WHO classification. Of these, 68.5% were never smokers and 31.4% current/former smokers; mean smoking duration 8±13 years. Most frequently altered genes were pTERT (63.6%), CDKN2A (39.7%), CDKN2B (38%), TP53 (33.2%), EGFR (31%), PTEN (31%), and IDH1 (20.7%). In all gliomas, alterations more frequent in smokers were TP53 (40.7% vs 26.9%, p=0.036, adjusted p=0.3) and RB1 (11.1% vs 0%, p<0.0009, adjusted p=0.02). In GBM, alterations in RB1 were more frequent in smokers (14.3% vs 0%, p<0.0051, adjusted p=0.14). In astrocytoma, TP53 alterations were more common in smokers (64.7% vs 29.2%, p=0.05, adjusted p=0.42). No differences were seen in oligodendroglioma. Median OS was shorter for smokers (46 vs 141 months, p=0.001) with 42% greater risk of death (HR 1.42, 95%CI 1.01–1.99, p=0.001), controlling for age and glioma diagnosis.
Conclusions:
Smokers have shorter survival from glioma. Differences in age and smoking-related genomic alterations may contribute to shortened survival.