Show simple item record

dc.contributor.authorKerns, S
dc.contributor.authorDorling, L
dc.contributor.authorFachal, L
dc.contributor.authorBentzen, S
dc.contributor.authorPharoah, P
dc.contributor.authorBarnes, D
dc.contributor.authorGómez-Caamaño, A
dc.contributor.authorCarballo, A
dc.contributor.authorDearnaley, D
dc.contributor.authorPeleteiro, P
dc.contributor.authorGulliford, S
dc.contributor.authorHall, E
dc.contributor.authorMichailidou, K
dc.contributor.authorCarracedo, Á
dc.contributor.authorSia, M
dc.contributor.authorStock, R
dc.contributor.authorStone, N
dc.contributor.authorSydes, M
dc.contributor.authorTyrer, J
dc.contributor.authorAhmed, S
dc.contributor.authorParliament, M
dc.contributor.authorOstrer, H
dc.contributor.authorRosenstein, B
dc.contributor.authorVega, A
dc.contributor.authorBurnet, N
dc.contributor.authorDunning, A
dc.contributor.authorBarnett, G
dc.contributor.authorWest, Catharine M L
dc.date.accessioned2016-10-05T11:26:22Z
dc.date.available2016-10-05T11:26:22Z
dc.date.issued2016-08
dc.identifier.citationMeta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer. 2016, 10:150-63 EBioMedicineen
dc.identifier.issn2352-3964
dc.identifier.pmid27515689
dc.identifier.doi10.1016/j.ebiom.2016.07.022
dc.identifier.urihttp://hdl.handle.net/10541/619930
dc.description.abstractNearly 50% of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients. We aimed to meta-analyze individual level data from four genome-wide association studies from prostate cancer radiotherapy cohorts including 1564 men to identify genetic markers of toxicity. Prospectively assessed two-year toxicity endpoints (urinary frequency, decreased urine stream, rectal bleeding, overall toxicity) and single nucleotide polymorphism (SNP) associations were tested using multivariable regression, adjusting for clinical and patient-related risk factors. A fixed-effects meta-analysis identified two SNPs: rs17599026 on 5q31.2 with urinary frequency (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.08-4.69, p-value 4.16×10(-8)) and rs7720298 on 5p15.2 with decreased urine stream (OR 2.71, 95% CI 1.90-3.86, p-value=3.21×10(-8)). These SNPs lie within genes that are expressed in tissues adversely affected by pelvic radiotherapy including bladder, kidney, rectum and small intestine. The results show that heterogeneous radiotherapy cohorts can be combined to identify new moderate-penetrance genetic variants associated with radiotherapy toxicity. The work provides a basis for larger collaborative efforts to identify enough variants for a future test involving polygenic risk profiling.
dc.language.isoenen
dc.rightsArchived with thanks to EBioMedicineen
dc.titleMeta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer.en
dc.typeArticleen
dc.contributor.departmentDepartment of Radiation Oncology, University of Rochester Medical Center, Rochester, NYen
dc.identifier.journalEBioMedicineen
refterms.dateFOA2018-12-17T14:39:46Z
html.description.abstractNearly 50% of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients. We aimed to meta-analyze individual level data from four genome-wide association studies from prostate cancer radiotherapy cohorts including 1564 men to identify genetic markers of toxicity. Prospectively assessed two-year toxicity endpoints (urinary frequency, decreased urine stream, rectal bleeding, overall toxicity) and single nucleotide polymorphism (SNP) associations were tested using multivariable regression, adjusting for clinical and patient-related risk factors. A fixed-effects meta-analysis identified two SNPs: rs17599026 on 5q31.2 with urinary frequency (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.08-4.69, p-value 4.16×10(-8)) and rs7720298 on 5p15.2 with decreased urine stream (OR 2.71, 95% CI 1.90-3.86, p-value=3.21×10(-8)). These SNPs lie within genes that are expressed in tissues adversely affected by pelvic radiotherapy including bladder, kidney, rectum and small intestine. The results show that heterogeneous radiotherapy cohorts can be combined to identify new moderate-penetrance genetic variants associated with radiotherapy toxicity. The work provides a basis for larger collaborative efforts to identify enough variants for a future test involving polygenic risk profiling.


Files in this item

Thumbnail
Name:
PIIS2352396416303279.pdf
Size:
724.6Kb
Format:
PDF
Description:
Open access full text article

This item appears in the following Collection(s)

Show simple item record