title: Genome-wide association study identifies a region on chromosome 11q14.3 associated with late rectal bleeding following radiation therapy for prostate cancer.
abstract: OBJECTIVE
  Rectal bleeding can occur following radiotherapy for prostate cancer and negatively impacts quality of life for cancer survivors. Treatment and clinical factors do not fully predict rectal bleeding, and genetic factors may be important.
  
  
  METHODS
  A genome-wide association study (GWAS) was performed to identify SNPs associated with the development of late rectal bleeding following radiotherapy for prostate cancer. Logistic regression was used to test the association between 614,453 SNPs and rectal bleeding in a discovery cohort (79 cases, 289 controls), and top-ranking SNPs were tested in a replication cohort (108 cases, 673 controls) from four independent sites.
  
  
  RESULTS
  rs7120482 and rs17630638, which tag a single locus on chromosome 11q14.3, reached genome-wide significance for association with rectal bleeding (combined p-values 5.4×10(-8) and 6.9×10(-7) respectively). Several other SNPs had p-values trending toward genome-wide significance, and a polygenic risk score including these SNPs shows a strong rank-correlation with rectal bleeding (Sommers' d=5.0×10(-12) in the replication cohort).
  
  
  CONCLUSIONS
  This GWAS identified novel genetic markers of rectal bleeding following prostate radiotherapy. These findings could lead to the development of a predictive assay to identify patients at risk for this adverse treatment outcome so that dose or treatment modality could be modified.
authors.affiliation: Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Kerns
authors.forename: Richard G
authors.initials: RG
authors.lastname: Stock
authors.forename: Nelson N
authors.initials: NN
authors.lastname: Stone
authors.forename: Seth R
authors.initials: SR
authors.lastname: Blacksburg
authors.forename: Lynda
authors.initials: L
authors.lastname: Rath
authors.forename: Ana
authors.initials: A
authors.lastname: Vega
authors.forename: Laura
authors.initials: L
authors.lastname: Fachal
authors.forename: Antonio
authors.initials: A
authors.lastname: Gómez-Caamaño
authors.forename: Dirk
authors.initials: D
authors.lastname: De Ruysscher
authors.forename: Guido
authors.initials: G
authors.lastname: Lammering
authors.forename: Matthew
authors.initials: M
authors.lastname: Parliament
authors.forename: Michael
authors.initials: M
authors.lastname: Blackshaw
authors.forename: Michael
authors.initials: M
authors.lastname: Sia
authors.forename: Jamie
authors.initials: J
authors.lastname: Cesaretti
authors.forename: Mitchell
authors.initials: M
authors.lastname: Terk
authors.forename: Rosetta
authors.initials: R
authors.lastname: Hixson
authors.forename: Barry S
authors.initials: BS
authors.lastname: Rosenstein
authors.forename: Harry
authors.initials: H
authors.lastname: Ostrer
mesh_terms: D000368:Aged; D002880:Chromosomes, Human, Pair 11; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D012002:Rectal Diseases / Q000209:etiology / Q000235:genetics*
keywords: Genome-wide association study; Prostate cancer; Radiogenomics; Rectal toxicity