A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of urinary symptoms after radiotherapy for prostate cancer

Sarah L. Kerns, Nelson N. Stone, Richard G. Stock, Lynda Rath, Harry Ostrer, Barry S. Rosenstein

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Purpose: We identified single nucleotide polymorphisms associated with change in the AUA Symptom Score after radiotherapy for prostate cancer. Materials and Methods: A total of 723 patients treated with brachytherapy with or without external beam radiation therapy were assessed at baseline and annually after radiotherapy using the AUA Symptom Score. A 2-stage genome-wide association study was performed with the primary end point of change in AUA Symptom Score from baseline at each of 4 followup periods. Single nucleotide polymorphism associations were assessed using multivariable linear regression adjusting for pre-radiotherapy AUA Symptom Score severity category and clinical variables. Fisher's trend method was used to calculate combined p values from the discovery and replication cohorts. Results: A region on chromosome 9p21.2 containing 8 single nucleotide polymorphisms showed the strongest association with change in AUA Symptom Score (combined p values 8.8×10-6 to 6.5×10-7 at 2 to 3 years after radiotherapy). These single nucleotide polymorphisms form a haplotype block that encompasses the inflammation signaling gene IFNK. These single nucleotide polymorphisms were independently associated with change in AUA Symptom Score after adjusting for clinical predictors including smoking history, hypertension, α-blocker use and pre-radiotherapy AUA Symptom Score. An additional 24 single nucleotide polymorphisms showed moderate significance for association with change in AUA Symptom Score. Several of these single nucleotide polymorphisms were more strongly associated with change in specific AUA Symptom Score items, including rs13035033 in the MYO3B gene, which was associated with straining (beta coefficient 0.9, 95% CI 0.6-1.2, p = 5.0×10-9). Conclusions: If validated, these single nucleotide polymorphisms could provide insight into the biology underlying urinary symptoms following radiotherapy and could lead to development of an assay to identify patients at risk for experiencing these effects.

Original languageEnglish (US)
Pages (from-to)102-108
Number of pages7
JournalJournal of Urology
Volume190
Issue number1
DOIs
StatePublished - Jul 2013

Fingerprint

Genome-Wide Association Study
Single Nucleotide Polymorphism
Prostatic Neoplasms
Radiotherapy
Brachytherapy
Haplotypes
Genes
Linear Models
Chromosomes
Smoking
History
Hypertension
Inflammation

Keywords

  • genome-wide association study
  • morbidity
  • prostatic neoplasms
  • radiotherapy

ASJC Scopus subject areas

  • Urology

Cite this

A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of urinary symptoms after radiotherapy for prostate cancer. / Kerns, Sarah L.; Stone, Nelson N.; Stock, Richard G.; Rath, Lynda; Ostrer, Harry; Rosenstein, Barry S.

In: Journal of Urology, Vol. 190, No. 1, 07.2013, p. 102-108.

Research output: Contribution to journalArticle

Kerns, Sarah L. ; Stone, Nelson N. ; Stock, Richard G. ; Rath, Lynda ; Ostrer, Harry ; Rosenstein, Barry S. / A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of urinary symptoms after radiotherapy for prostate cancer. In: Journal of Urology. 2013 ; Vol. 190, No. 1. pp. 102-108.
@article{5f8842ba7ac94fcb8e087afb55244c68,
title = "A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of urinary symptoms after radiotherapy for prostate cancer",
abstract = "Purpose: We identified single nucleotide polymorphisms associated with change in the AUA Symptom Score after radiotherapy for prostate cancer. Materials and Methods: A total of 723 patients treated with brachytherapy with or without external beam radiation therapy were assessed at baseline and annually after radiotherapy using the AUA Symptom Score. A 2-stage genome-wide association study was performed with the primary end point of change in AUA Symptom Score from baseline at each of 4 followup periods. Single nucleotide polymorphism associations were assessed using multivariable linear regression adjusting for pre-radiotherapy AUA Symptom Score severity category and clinical variables. Fisher's trend method was used to calculate combined p values from the discovery and replication cohorts. Results: A region on chromosome 9p21.2 containing 8 single nucleotide polymorphisms showed the strongest association with change in AUA Symptom Score (combined p values 8.8×10-6 to 6.5×10-7 at 2 to 3 years after radiotherapy). These single nucleotide polymorphisms form a haplotype block that encompasses the inflammation signaling gene IFNK. These single nucleotide polymorphisms were independently associated with change in AUA Symptom Score after adjusting for clinical predictors including smoking history, hypertension, α-blocker use and pre-radiotherapy AUA Symptom Score. An additional 24 single nucleotide polymorphisms showed moderate significance for association with change in AUA Symptom Score. Several of these single nucleotide polymorphisms were more strongly associated with change in specific AUA Symptom Score items, including rs13035033 in the MYO3B gene, which was associated with straining (beta coefficient 0.9, 95{\%} CI 0.6-1.2, p = 5.0×10-9). Conclusions: If validated, these single nucleotide polymorphisms could provide insight into the biology underlying urinary symptoms following radiotherapy and could lead to development of an assay to identify patients at risk for experiencing these effects.",
keywords = "genome-wide association study, morbidity, prostatic neoplasms, radiotherapy",
author = "Kerns, {Sarah L.} and Stone, {Nelson N.} and Stock, {Richard G.} and Lynda Rath and Harry Ostrer and Rosenstein, {Barry S.}",
year = "2013",
month = "7",
doi = "10.1016/j.juro.2013.01.096",
language = "English (US)",
volume = "190",
pages = "102--108",
journal = "Journal of Urology",
issn = "0022-5347",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of urinary symptoms after radiotherapy for prostate cancer

AU - Kerns, Sarah L.

AU - Stone, Nelson N.

AU - Stock, Richard G.

AU - Rath, Lynda

AU - Ostrer, Harry

AU - Rosenstein, Barry S.

PY - 2013/7

Y1 - 2013/7

N2 - Purpose: We identified single nucleotide polymorphisms associated with change in the AUA Symptom Score after radiotherapy for prostate cancer. Materials and Methods: A total of 723 patients treated with brachytherapy with or without external beam radiation therapy were assessed at baseline and annually after radiotherapy using the AUA Symptom Score. A 2-stage genome-wide association study was performed with the primary end point of change in AUA Symptom Score from baseline at each of 4 followup periods. Single nucleotide polymorphism associations were assessed using multivariable linear regression adjusting for pre-radiotherapy AUA Symptom Score severity category and clinical variables. Fisher's trend method was used to calculate combined p values from the discovery and replication cohorts. Results: A region on chromosome 9p21.2 containing 8 single nucleotide polymorphisms showed the strongest association with change in AUA Symptom Score (combined p values 8.8×10-6 to 6.5×10-7 at 2 to 3 years after radiotherapy). These single nucleotide polymorphisms form a haplotype block that encompasses the inflammation signaling gene IFNK. These single nucleotide polymorphisms were independently associated with change in AUA Symptom Score after adjusting for clinical predictors including smoking history, hypertension, α-blocker use and pre-radiotherapy AUA Symptom Score. An additional 24 single nucleotide polymorphisms showed moderate significance for association with change in AUA Symptom Score. Several of these single nucleotide polymorphisms were more strongly associated with change in specific AUA Symptom Score items, including rs13035033 in the MYO3B gene, which was associated with straining (beta coefficient 0.9, 95% CI 0.6-1.2, p = 5.0×10-9). Conclusions: If validated, these single nucleotide polymorphisms could provide insight into the biology underlying urinary symptoms following radiotherapy and could lead to development of an assay to identify patients at risk for experiencing these effects.

AB - Purpose: We identified single nucleotide polymorphisms associated with change in the AUA Symptom Score after radiotherapy for prostate cancer. Materials and Methods: A total of 723 patients treated with brachytherapy with or without external beam radiation therapy were assessed at baseline and annually after radiotherapy using the AUA Symptom Score. A 2-stage genome-wide association study was performed with the primary end point of change in AUA Symptom Score from baseline at each of 4 followup periods. Single nucleotide polymorphism associations were assessed using multivariable linear regression adjusting for pre-radiotherapy AUA Symptom Score severity category and clinical variables. Fisher's trend method was used to calculate combined p values from the discovery and replication cohorts. Results: A region on chromosome 9p21.2 containing 8 single nucleotide polymorphisms showed the strongest association with change in AUA Symptom Score (combined p values 8.8×10-6 to 6.5×10-7 at 2 to 3 years after radiotherapy). These single nucleotide polymorphisms form a haplotype block that encompasses the inflammation signaling gene IFNK. These single nucleotide polymorphisms were independently associated with change in AUA Symptom Score after adjusting for clinical predictors including smoking history, hypertension, α-blocker use and pre-radiotherapy AUA Symptom Score. An additional 24 single nucleotide polymorphisms showed moderate significance for association with change in AUA Symptom Score. Several of these single nucleotide polymorphisms were more strongly associated with change in specific AUA Symptom Score items, including rs13035033 in the MYO3B gene, which was associated with straining (beta coefficient 0.9, 95% CI 0.6-1.2, p = 5.0×10-9). Conclusions: If validated, these single nucleotide polymorphisms could provide insight into the biology underlying urinary symptoms following radiotherapy and could lead to development of an assay to identify patients at risk for experiencing these effects.

KW - genome-wide association study

KW - morbidity

KW - prostatic neoplasms

KW - radiotherapy

UR - http://www.scopus.com/inward/record.url?scp=84878825562&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878825562&partnerID=8YFLogxK

U2 - 10.1016/j.juro.2013.01.096

DO - 10.1016/j.juro.2013.01.096

M3 - Article

VL - 190

SP - 102

EP - 108

JO - Journal of Urology

JF - Journal of Urology

SN - 0022-5347

IS - 1

ER -