Dataset Information

G(2) chromosomal radiosensitivity in Danish survivors of childhood and adolescent cancer and their offspring.

ABSTRACT: In order to investigate the relationship between chromosomal radiosensitivity and early-onset cancer, the G(2) chromosomal radiosensitivity assay was undertaken on a group of 23 Danish survivors of childhood and adolescent cancer, a control group comprising their partners and a group of 38 of their offspring. In addition, the previously reported in-house control group from Westlakes Research Institute (WRI) was extended to 27 individuals. When using the 90th percentile cutoff for the WRI control group, the proportion of individuals with elevated radiosensitivity was 11, 35, 52 and 53% for the WRI control, partner control, cancer survivor and the offspring groups, respectively, with significant differences between the WRI control group and the cancer survivor group (P=0.002) and the offspring group (P<0.001). However, while the comparisons with the WRI control group support an association of chromosomal radiosensitivity with cancer predisposition, when the partner control group was used to define the radiosensitivity cutoff point, no significant differences in radiosensitivity profiles were found between the partner control group and either the cancer survivor group or the offspring group. The failure to distinguish between the G(2) aberration profiles of the apparently normal group of partners and the cancer survivor group suggests that any association with cancer should be viewed with caution, but also raises questions as to the suitability of the partners of cancer survivors to act as an appropriate control group. Heritability of the radiosensitive phenotype was examined by segregation analysis of the Danish families and suggested that 67.3% of the phenotypic variance of G(2) chromosomal radiosensitivity is attributable to a putative major gene locus with dominant effect.

SUBMITTER: Curwen GB

PROVIDER: S-EPMC2361675 | biostudies-other | 2005 Oct

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:ImportanceCertain cancer therapies are risk factors for epigenetic age acceleration (EAA) among survivors of childhood cancer, and EAA is associated with chronic health conditions (CHCs). However, small numbers of younger survivors (aged <20 years) previously evaluated have limited the ability to calculate EAA among this age group.ObjectiveTo evaluate the change rate of epigenetic age (EA) and EAA in younger compared with older survivors and the possible association of EAA with early-onset obesity (aged <20 years), severity/burden of CHCs, and late mortality (>5 years from cancer diagnosis).Design, setting, and participantsStudy participants were from the St Jude Lifetime Cohort, initiated in 2007 with ongoing follow-up. The present study was conducted from April 17, 2022, to March 23, 2023. Survivors in this cohort of European ancestry with DNA methylation data were included. Cross-sectional annual changes in EA and EAA were compared across 5 different chronologic age groups: age 0 to 9 (children), 10 to 19 (adolescents), 20 to 34 (younger adults), 35 to 49 (middle-aged adults), and greater than or equal to 50 (older adults) years. Logistic regression evaluated the association between EAA and early-onset obesity or severity/burden of CHCs. Cox proportional hazards regression assessed the association between EAA and late mortality.Main outcomes and measuresEarly-onset obesity, severity/burden of CHCs (graded using the Common Terminology Criteria for Adverse Events (grade 1, mild; 2, moderate; 3, severe/disabling; 4, life-threatening) and were combined into high vs low severity/burden based on frequency and grade), and late mortality were the outcomes based on follow-up until April 2020. Expanded DNA methylation profiling increased the number of survivors younger than 20 years (n = 690). Epigenetic age was calculated primarily using the Levine clock, and EAA was derived from least squares regression of EA against chronologic age and was standardized to a z score (Levine EEA).ResultsAmong 2846 participants (median age, 30.3 [IQR, 9.3-41.5] years; 53% males), the cross-sectional annual change in EA_Levine was higher in children (1.63 years) and adolescents (1.14 years), and the adjusted least-squares mean of Levine EEA was lower in children (-0.22 years) and older adults (-1.70 years). Each 1-SD increase in Levine EEA was associated with increased risk of developing early-onset obesity (odds ratio [OR], 1.46; 95% CI, 1.19-1.78), high severity/burden of CHCs (OR, 1.13; 95% CI, 1.03-1.24), and late mortality (hazard ratio, 1.75; 95% CI, 1.35-2.26).Conclusions and relevanceThe findings of this study suggest that EAA measured in children and adolescent survivors of childhood cancer is associated with early-onset obesity, severity/burden of all CHCs, and late mortality. Evaluating EAA may help identify survivors of childhood cancer at increased risk for early-onset obesity, morbidity in general, and mortality.

Dataset Information

G(2) chromosomal radiosensitivity in Danish survivors of childhood and adolescent cancer and their offspring.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets