P1.17-03 Potential Associated SNPs by GWAS with Radiation Pneumonitis (RP) in Patients with Lung Cancer Treated with Radiotherapy

Lung cancer is one of the most prevalent cancers and the leading cause of cancer-related deaths in China and worldwide. Radiation therapy plays a remarkable role in lung cancer treatment, and approximately 60%∼70% lung cancer patients receive radiation treatment. Whereas, radiation pneumonitis is one of the most critical dose-limiting toxicities of thoracic radiation. Single nucleotide polymorphisms (SNPs) in inflammation-related, DNA repair-related, oxidative stress response-related and angiogenesis-related genes and so on were proved to be associated with RP, with different underlying mechanisms. Previous limited studies reported few SNP sites that may be used a biomarker for prediction of RP risk. However these studies mainly focused on previously reported sites and only limited sites were tested. Here, the purpose of this study was to evaluate the potential related SNPs by whole genome sequencing and radiation pneumonitis (RP) development. We recruited a total of 132 patients with lung cancer receiving intensity modulated radiation therapy (IMRT). We collected the blood sample and sequenced the whole genomes in all patients. RP events were prospectively scored using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Kaplan-Meier analysis was used to determine the cumulative probability of RP of grade ≥ 2. Genomes-Wide Association Study (GWAS) was carried out to look for potential SNPs associated with risk of RP grade ≥ 2. The incidence of RP of grade ≥ 2 was 29.2%. Using SNP information by Genomes-Wide Association Study (GWAS), we discovered 73 SNPs that showed significant difference with cutting off p-value of 0.001. Most of them are previously not reported. This result established a set of biomarkers which can be used for prognosis predictions for radiation-induced pneumonitis.