P10.18.A Replication of previous GWAS identifies TERT and near EGFR SNVs as risk factors in EPIC glioma patients: a nested case-control study

Abstract

Abstract Background Gliomas, the most common malignant primary brain tumors in adults, typically have a poor prognosis irrespective of medical care. Previous large genome-wide association studies (GWAS) have identified 27 single-nucleotide variants (SNVs) that are significantly associated with glioma. However, most of the GWAS are conducted by case-control study designs, it is therefore prone to bias when rapidly lethal cases don’t have chance to be included in the study. This study aims to replicate the previous GWAS findings using prospective study design. Material and Methods We conducted a nested case-control study within the European Prospective Investigation into Cancer (EPIC) cohort from 7 European countries. GSA-MD Infinium global screening array was used for genotyping. Some subjects were genotyped by other platforms previously. In total, 468 glioma patients and 481 controls were included. The genotypes of 27 SNVs were extracted and for ungenotyped SNVs, datasets were imputed using SHAPEIT v4.1.3 and IMPUTE5 v1.1.5 based on the Haplotype Reference Consortium (Release 1.1) reference panel. Conditional logistic regression model was used to investigate the additive effect of SNVs on the risk of glioma. Results 21 SNVs showed a consistent direction of effect with previous studies, whereas 6 SNVs did not (ORs between 0.72-0.99 and not significant). After adjusting for multiple testing, two SNVs, rs10069690 (TERT), and rs75061358 (near EGFR) were significantly associated with glioma risk. We observed that prominent OR (2.23, 95%CI=1.49-3.33) of rs75061358 in our study compared to the result from previous GWAS, which implied rs75061358 might be not only a risk factor but also affect survival. Different risk direction was observed for rs77633900 in ETFA gene (OR=0.72, 95%CI=0.51-1.01). Conclusion Our findings further confirmed the genetic role on the etiology of glioma in the European population. The potential biases from the previous GWAS are required to be elucidated.