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

Sarah L. Kerns, Richard G. Stock, Nelson N. Stone, Seth R. Blacksburg, Lynda Rath, Ana Vega, Laura Fachal, Antonio Gómez-Caamaño, Dirk De Ruysscher, Guido Lammering, Matthew Parliament, Michael Blackshaw, Michael Sia, Jamie Cesaretti, Mitchell Terk, Rosetta Hixson, Barry S. Rosenstein, Harry Ostrer

Research output: Contribution to journalArticle

56 Citations (Scopus)

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 5.4 × 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.

Original languageEnglish (US)
Pages (from-to)372-376
Number of pages5
JournalRadiotherapy and Oncology
Volume107
Issue number3
DOIs
StatePublished - Jun 2013

Fingerprint

Genome-Wide Association Study
Prostatic Neoplasms
Radiotherapy
Chromosomes
Hemorrhage
Single Nucleotide Polymorphism
Genome
Genetic Markers
Survivors
Prostate
Logistic Models
Quality of Life
Therapeutics
Neoplasms

Keywords

  • Genome-wide association study
  • Prostate cancer
  • Radiogenomics
  • Rectal toxicity

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Hematology

Cite this

Genome-wide association study identifies a region on chromosome 11q14.3 associated with late rectal bleeding following radiation therapy for prostate cancer. / Kerns, Sarah L.; Stock, Richard G.; Stone, Nelson N.; Blacksburg, Seth R.; Rath, Lynda; Vega, Ana; Fachal, Laura; Gómez-Caamaño, Antonio; De Ruysscher, Dirk; Lammering, Guido; Parliament, Matthew; Blackshaw, Michael; Sia, Michael; Cesaretti, Jamie; Terk, Mitchell; Hixson, Rosetta; Rosenstein, Barry S.; Ostrer, Harry.

In: Radiotherapy and Oncology, Vol. 107, No. 3, 06.2013, p. 372-376.

Research output: Contribution to journalArticle

Kerns, SL, Stock, RG, Stone, NN, Blacksburg, SR, Rath, L, Vega, A, Fachal, L, Gómez-Caamaño, A, De Ruysscher, D, Lammering, G, Parliament, M, Blackshaw, M, Sia, M, Cesaretti, J, Terk, M, Hixson, R, Rosenstein, BS & Ostrer, H 2013, 'Genome-wide association study identifies a region on chromosome 11q14.3 associated with late rectal bleeding following radiation therapy for prostate cancer', Radiotherapy and Oncology, vol. 107, no. 3, pp. 372-376. https://doi.org/10.1016/j.radonc.2013.05.001
Kerns, Sarah L. ; Stock, Richard G. ; Stone, Nelson N. ; Blacksburg, Seth R. ; Rath, Lynda ; Vega, Ana ; Fachal, Laura ; Gómez-Caamaño, Antonio ; De Ruysscher, Dirk ; Lammering, Guido ; Parliament, Matthew ; Blackshaw, Michael ; Sia, Michael ; Cesaretti, Jamie ; Terk, Mitchell ; Hixson, Rosetta ; Rosenstein, Barry S. ; Ostrer, Harry. / Genome-wide association study identifies a region on chromosome 11q14.3 associated with late rectal bleeding following radiation therapy for prostate cancer. In: Radiotherapy and Oncology. 2013 ; Vol. 107, No. 3. pp. 372-376.
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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 5.4 × 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.",
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T1 - Genome-wide association study identifies a region on chromosome 11q14.3 associated with late rectal bleeding following radiation therapy for prostate cancer

AU - Kerns, Sarah L.

AU - Stock, Richard G.

AU - Stone, Nelson N.

AU - Blacksburg, Seth R.

AU - Rath, Lynda

AU - Vega, Ana

AU - Fachal, Laura

AU - Gómez-Caamaño, Antonio

AU - De Ruysscher, Dirk

AU - Lammering, Guido

AU - Parliament, Matthew

AU - Blackshaw, Michael

AU - Sia, Michael

AU - Cesaretti, Jamie

AU - Terk, Mitchell

AU - Hixson, Rosetta

AU - Rosenstein, Barry S.

AU - Ostrer, Harry

PY - 2013/6

Y1 - 2013/6

N2 - 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 5.4 × 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.

AB - 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 5.4 × 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.

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