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Genome-wide association study identifies a region on chromosome 11q14.3 associated with late rectal bleeding following radiation therapy for prostate cancer

Kerns, S. L.; Stock, R. G.; Stone, N. N.; Blacksburg, S. R.; Rath, L.; Vega Gliemmo, Ana; Fachal Vilar, Laura; Gómez Caamaño, Antonio; De Ruysscher, D.; Lammering, G.; Parliament, M.; Blackshaw, M.; Sia, M.; Cesaretti, J.; Terk, M.; Hixson, R.; Rosenstein, B. S.; Ostrer, H.
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URI: http://hdl.handle.net/20.500.11940/3558
PMID: 23719583
DOI: 10.1016/j.radonc.2013.05.001
ISSN: 0167-8140
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Radiother Oncol . 2013 Jun;107(3):372-6 (142.1Kb)
Date issued
2013
Journal title
RADIOTHERAPY AND ONCOLOGY
Type of content
Artigo
MeSH
Aged | Chromosomes, Human, Pair 11 | Gastrointestinal Hemorrhage | Genome-Wide Association Study | Humans | Logistic Models | Male | Middle Aged | Polymorphism, Single Nucleotide | Prostatic Neoplasms | Rectal Diseases | Genome-wide association study | Prostate cancer | Radiogenomics | Rectal toxicity
Abstract
BACKGROUND AND PURPOSE: 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. MATERIALS AND 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 5.4x10(-8) and 6.9x10(-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=5.0x10(-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.

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