asco@alo33:161479 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/asco@alo33/sourceid/161479","sourcedb":"asco@alo33","sourceid":"161479","text":" Background: Contemporary therapies produce high cure rates in HL. Hoever, complications of treatment produce substantial morbidity and mortality. Identification of individuals at high risk for toxicity is a goal for precision HL therapy. Methods: We conducted a nested case-control study of 953 intermediate risk HL patients enrolled on the Childrens Oncology Group AHOD0031 protocol, assessing associations beteen severe lung toxicity and clinical, demographic, x0026; genetic predictors. Chemotherapy included doxorubicin, bleomycin, vincristine, etoposide, cyclophosphamide, and prednisone. The frequency of 1936 variant alleles 1931 SNPs x0026; 5 CNVs in 225 drug metabolism enzyme and transporter genes ere compared beteen patients ith nomild n=929 x0026; severe n=24 lung toxicities. Significant polymorphisms plt0.005 ere combined into per-individual risk scores by summing risk alleles, and included in a predictive regression model ith significant covariates. Results: We found a significant association beteen severe lung toxicity and polymorphisms in 3 genes; NAT2, SLCO1B1x0026;ABCC1. Risk alleles ere summed across the 3 polymorphisms, generating an allelic risk score ranging from 0-5. A regression model for prediction of lung toxicity included allelic risk score and erythrocyte sedimentation rate ESR . The model identified a high-risk group ith severe lung toxicity prevalence of 9 percent, and a lo-risk group ith prevalence of 1.5 percent. Within the high-risk subset, a second-stage test of polymorphisms in GSTA4 and SLCO1B1 identified a subset ith a prevalence of 28 percent. Within the lo-risk subset, polymorphisms in CYP11B1, SLC7A8, and SLCO1B1 identified individuals ith a prevalence of 8 percent. To validate the results, e retested the model in 1000 bootstrapped data sets generated from the original data. Conclusions: A to-step algorithm combining genetic risk alleles in 8 polymorphisms, integrated ith ESR, identifies HL patients at lo lt1.5 percent and high 28 percent risk for severe pulmonary toxicities. These results suggest potential for genomic-guided therapy regimen assignment to avoid drugs eg bleomycin associated ith lung toxicity in high risk patients. This ork serves as a model for approaches to other HL toxicities.,J Clin Oncol 34, 2016 suppl; abstr 7522 00:00.0,Hematologic MalignanciesLymphoma and Chronic Lymphocytic Leukemia \n","tracks":[{"project":"ASCO_abstracts","denotations":[{"id":"T1","span":{"begin":64,"end":66},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":228,"end":230},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":315,"end":317},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":424,"end":428},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":781,"end":785},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":1037,"end":1041},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":1247,"end":1251},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T8","span":{"begin":1381,"end":1385},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T9","span":{"begin":1966,"end":1968},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T10","span":{"begin":2184,"end":2188},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T11","span":{"begin":2272,"end":2274},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T12","span":{"begin":2373,"end":2401},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0004952"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0004952"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0004952"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"0021117"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"0021117"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"0021117"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"0021117"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"0021117"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"0004952"},{"id":"A10","pred":"mondo_id","subj":"T10","obj":"0021117"},{"id":"A11","pred":"mondo_id","subj":"T11","obj":"0004952"},{"id":"A12","pred":"mondo_id","subj":"T12","obj":"0004948"},{"subj":"T1","pred":"source","obj":"ASCO_abstracts"},{"subj":"T2","pred":"source","obj":"ASCO_abstracts"},{"subj":"T3","pred":"source","obj":"ASCO_abstracts"},{"subj":"T4","pred":"source","obj":"ASCO_abstracts"},{"subj":"T5","pred":"source","obj":"ASCO_abstracts"},{"subj":"T6","pred":"source","obj":"ASCO_abstracts"},{"subj":"T7","pred":"source","obj":"ASCO_abstracts"},{"subj":"T8","pred":"source","obj":"ASCO_abstracts"},{"subj":"T9","pred":"source","obj":"ASCO_abstracts"},{"subj":"T10","pred":"source","obj":"ASCO_abstracts"},{"subj":"T11","pred":"source","obj":"ASCO_abstracts"},{"subj":"T12","pred":"source","obj":"ASCO_abstracts"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"ASCO_abstracts","color":"#93ec99","default":true}]}]}}