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Effect of Temporal Changes in Therapeutic Exposure on Self-reported Health Status in Childhood Cancer Survivors.

ABSTRACT: The effect of temporal changes in cancer therapy on health status among childhood cancer survivors has not been evaluated.To compare proportions of self-reported adverse health status outcomes among childhood cancer survivors across 3 decades.Cross-sectional. (ClinicalTrials.gov: NCT01120353).27 North American institutions.14 566 adults, who survived for 5 or more years after initial diagnosis (median age, 27 years; range, 18 to 48 years), treated from 1970 to 1999.Patient report of poor general or mental health, functional impairment, activity limitation, or cancer-related anxiety or pain was evaluated as a function of treatment decade, cancer treatment exposure, chronic health conditions, demographic characteristics, and health habits.Despite reductions in late mortality and the proportions of survivors with severe, disabling, or life-threatening chronic health conditions (33.4% among those treated from 1970 to 1979 and 21.0% among those treated from 1990 to 1999), those reporting adverse health status did not decrease by treatment decade. Compared with survivors diagnosed in 1970 to 1979, those diagnosed in 1990 to 1999 were more likely to report poor general health (11.2% vs. 13.7%; P < 0.001) and cancer-related anxiety (13.3% vs. 15.0%; P < 0.001). From 1970 to 1979 and 1990 to 1999, the proportions of survivors reporting adverse outcomes were higher (P < 0.001) among those with leukemia (poor general health, 9.5% and 13.9%) and osteosarcoma (pain, 23.9% and 36.6%). Temporal changes in treatment exposures were not associated with changes in the proportions of survivors reporting adverse health status. Smoking, not meeting physical activity guidelines, and being either underweight or obese were associated with poor health status.Considerable improvement in survival among children diagnosed with cancer in the 1990s compared with those diagnosed in the 1970s makes it difficult to definitively determine the effect of risk factors on later self-reported health status without considering their effect on mortality.Because survival rates after a diagnosis of childhood cancer have improved substantially over the past 30 years, the population of survivors now includes those who would have died in earlier decades. Self-reported health status among survivors has not improved despite evolution of treatment designed to reduce toxicities.The National Cancer Institute.

SUBMITTER: Ness KK

PROVIDER: S-EPMC5239750 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Effect of Temporal Changes in Therapeutic Exposure on Self-reported Health Status in Childhood Cancer Survivors.

Ness Kirsten K KK Hudson Melissa M MM Jones Kendra E KE Leisenring Wendy W Yasui Yutaka Y Chen Yan Y Stovall Marilyn M Gibson Todd M TM Green Daniel M DM Neglia Joseph P JP Henderson Tara O TO Casillas Jacqueline J Ford Jennifer S JS Effinger Karen E KE Krull Kevin R KR Armstrong Gregory T GT Robison Leslie L LL Oeffinger Kevin C KC Nathan Paul C PC

Annals of internal medicine 20161108 2

<h4>Background</h4>The effect of temporal changes in cancer therapy on health status among childhood cancer survivors has not been evaluated.<h4>Objective</h4>To compare proportions of self-reported adverse health status outcomes among childhood cancer survivors across 3 decades.<h4>Design</h4>Cross-sectional. (ClinicalTrials.gov: NCT01120353).<h4>Setting</h4>27 North American institutions.<h4>Participants</h4>14 566 adults, who survived for 5 or more years after initial diagnosis (median age, 2 ...[more]

PMID: 27820947

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Project description:Childhood maltreatment is highly prevalent and serves as a risk factor for mental and physical disorders. Self-reported childhood maltreatment appears heritable, but the specific genetic influences on this phenotype are largely unknown. The aims of this study were to (1) identify genetic variation associated with self-reported childhood maltreatment, (2) estimate SNP-based heritability (h2snp), (3) assess predictive value of polygenic risk scores (PRS) for childhood maltreatment, and (4) quantify genetic overlap of childhood maltreatment with mental and physical health-related phenotypes, and condition the top hits from our analyses when such overlap is present. Genome-wide association analysis for childhood maltreatment was undertaken, using a discovery sample from the UK Biobank (UKBB) (n = 124,000) and a replication sample from the Psychiatric Genomics Consortium-posttraumatic stress disorder group (PGC-PTSD) (n = 26,290). h2snp for childhood maltreatment and genetic correlations with mental/physical health traits were calculated using linkage disequilibrium score regression. PRS was calculated using PRSice and mtCOJO was used to perform conditional analysis. Two genome-wide significant loci associated with childhood maltreatment (rs142346759, p = 4.35 × 10-8, FOXP1; rs10262462, p = 3.24 × 10-8, FOXP2) were identified in the discovery dataset but were not replicated in PGC-PTSD. h2snp for childhood maltreatment was ~6% and the PRS derived from the UKBB was significantly predictive of childhood maltreatment in PGC-PTSD (r2 = 0.0025; p = 1.8 × 10-15). The most significant genetic correlation of childhood maltreatment was with depressive symptoms (rg = 0.70, p = 4.65 × 10-40), although we show evidence that our top hits may be specific to childhood maltreatment. This is the first large-scale genetic study to identify specific variants associated with self-reported childhood maltreatment. Speculatively, FOXP genes might influence externalizing traits and so be relevant to childhood maltreatment. Alternatively, these variants may be associated with a greater likelihood of reporting maltreatment. A clearer understanding of the genetic relationships of childhood maltreatment, including particular abuse subtypes, with a range of phenotypes, may ultimately be useful in in developing targeted treatment and prevention strategies.

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Dataset Information

Effect of Temporal Changes in Therapeutic Exposure on Self-reported Health Status in Childhood Cancer Survivors.

Publications

Effect of Temporal Changes in Therapeutic Exposure on Self-reported Health Status in Childhood Cancer Survivors.

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