Genetic Predictors of Adverse Radiotherapy Effects (Gene-PARE)

The goal of this study was to identify SNPs and CNPs that are associated with development of normal tissue toxicities resulting from radiotherapy for prostate cancer. The study population includes approximately 1,400 men treated with brachytherapy, external beam radiation therapy, or a combination of the two treatments, and assessed for adverse effects at baseline and following radiotherapy. Three toxicity endpoints were investigated using a two-stage GWAS approach: urinary morbidity, rectal bleeding and erectile dysfunction. The study sample was split into a discovery set (N=367) and a replication set (N=417), and an additional 647 samples, which were not part of this original cohort, were also included as an independent replication set. The replication set was developed via collaboration developed under the framework of the Radiogenomics Consortium (RGC). The long-term goal of this project, and other radiogenomics projects lead by the RGC, is two-fold: 1) Develop an assay capable of predicting which cancer patients are most likely to develop radiation injuries resulting from treatment with a standard RT protocol, and 2) Obtain information to assist with the elucidation of the molecular pathways responsible for radiation-induced normal tissue toxicities. These studies focus on multiple cancer types including prostate, breast, lung, and head and neck cancers.]]>
Eligible participants were men who were diagnosed with prostate adenocarcinoma and sought treatment at the Department of Radiation Oncology at the Mount Sinai Medical Center. Patients included in genotyping had a minimum of one year follow-up post-RT for at least one of the three toxicity endpoints of interest. Each toxicity endpoint had its own inclusion/exclusion criteria and case/control definition as follows: 1) Erectile Dysfunction - Patients were included if they had a baseline erectile function score available that indicated adequate function (IIEF score ≥ 16 or MSEF score ≥ 2) and at least one year of follow-up with the IIEF questionnaire. Patients were excluded if they received hormone therapy and their testosterone level remained < 50ng/dl by one year post-RT. Cases were those who had an IIEF score ≤ 7 at any point between one and five years post-RT. Controls were those whose IIEF score remained ≥ 16 throughout this follow-up period. Patients whose scores fell in the intermediate range (8-15) were excluded from the primary analysis. 2) Urinary Morbidity - Patients were included if they had a baseline AUASS assessment available and at least one year of follow-up with the AUASS questionnaire. Urinary Morbidity was treated as a quantitative trait, based on the change in AUASS relative to baseline. 3) Rectal Bleeding - All patients with at least one year of follow-up were included for this endpoint. Cases had RTOG grade ≥ 2 rectal bleeding and controls had RTOG grade ≤ 1 rectal bleeding.]]>