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dc.contributor.authorKerns, S. L.
dc.contributor.authorBarnett, G.
dc.contributor.authorDorling, L.
dc.contributor.authorFachal, L.
dc.contributor.authorMartinez-Calvo, L.
dc.contributor.authorAguado-Barrera, M. E.
dc.contributor.authorDearnaley, D
dc.contributor.authorColes, C. E.
dc.contributor.authorBurnet, Neil G
dc.contributor.authorWebb, A.
dc.contributor.authorDe Ruysscher, D
dc.contributor.authorSeibold, P.
dc.contributor.authorChang-Claude, J.
dc.contributor.authorParliament, M. B.
dc.contributor.authorUsmani, N. H.
dc.contributor.authorde Ruyck, K.
dc.contributor.authorRosenstein, B. S.
dc.contributor.authorDunning, A.
dc.contributor.authorVega, A.
dc.contributor.authorWest, Catharine M L
dc.date.accessioned2021-01-06T11:15:15Z
dc.date.available2021-01-06T11:15:15Z
dc.date.issued2020en
dc.identifier.citationKerns SL, Barnett G, Dorling L, Fachal L, Martinez-Calvo L, Aguado-Barrera M, et al. Do polygenic risk scores for cancer susceptibility associate with risk of radiotherapy toxicity. International Journal of Radiation Oncology Biology Physics. 2020;108(3):E513-Een
dc.identifier.urihttp://hdl.handle.net/10541/623577
dc.description.abstractPurpose/Objective(s): Single nucleotide polymorphisms (SNPs) associated with increased susceptibility to cancer frequently lie in genes that might also modulate response to radiation. The purpose of this study is to evaluate whether individuals at increased genetic risk of developing cancer are also more likely to develop late radiotherapy-induced toxicities. We test the hypothesis that polygenic risk scores (PRS) for cancer susceptibility alter toxicity risk among cancer patients who received radiotherapy. Materials/Methods: Analysis included 1,134 breast, 3,521 prostate, and 610 lung cancer patients from radiotherapy cohorts from the Radiogenomics and REQUITE Consortia. All patients received radiotherapy alone or as part of combination treatment and were followed prospectively for development of toxicity in relevant tissues. Germline DNA was genotyped using a genome-wide SNP array with non-typed SNPs imputed using the 1000 Genomes reference data. A PRS was generated for each patient by summing risk alleles from cancer susceptibility SNPs identified in the literature - 352 for breast, 147 for prostate, 24 for lung cancer. A weighted PRS was similarly generated for prostate and lung cancer in which each SNP was first weighted by its odds ratio for cancer susceptibility; such a score was not available for breast cancer as the odds ratios vary by estrogen receptor status. Toxicity was quantified for each patient using STAT score, which is a previously validated measure of overall radiotherapy toxicity that combines multiple individual endpoints. Multivariable logistic regression tested association between PRS and toxicity STAT score (dichotomized at the mean plus one standard deviation) at 2 years after treatment for breast and prostate and up to 1 year for lung cancer patients, controlling for clinical covariates. Individual SNPs comprising the PRS were tested in a secondary analysis. Results: No association was found between PRS and development of late radiotherapy toxicity among breast (PRS OR Z 1.01, 95% CI Z 1.00 to 1.02), prostate (PRS OR Z 1.01, 95% CI Z 1.00 to 1.03; weighted PRS OR Z 1.10, 95%CI Z 0.94 to 1.28) or lung cancer patients (PRS OR Z 0.95, 95% CI Z 0.88 to 1.02; weighted PRS OR Z 0.77, 95% CI Z 0.51 to 1.14). On multivariable analysis of individual SNPs, rs138944387 was associated with breast pain (beta Z 1.12; 95% CI Z 0.62 to 1.61; p Z 1.09x10-5) and rs17513613 was associated with risk of breast edema (beta Z -0.21; 95% CI Z -0.31 to -0.12; p Z 2.01x10-5). Conclusion: Cancer patients with a high polygenic predisposition to breast, prostate or lung cancer show no evidence of an increased risk of late radiotherapy toxicity. Thus, these patients can undergo standard treatment without an anticipated excess toxicity risk. The association between individual SNPs and late toxicity requires validation in independent cohorts and functional studies to elucidate the biologic mechanism underlying this shared risk.en
dc.language.isoenen
dc.titleDo polygenic risk scores for cancer susceptibility associate with risk of radiotherapy toxicityen
dc.typeMeetings and Proceedingsen
dc.contributor.departmentUniversity of Rochester Medical Center, Rochesteren
dc.identifier.journalInternational Journal of Radiation Oncology Biology Physicsen
dc.description.noteen]


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