Heritability of radiation response in lung cancer families.
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ABSTRACT:
SUBMITTER: Rosenberger A
PROVIDER: S-EPMC3899950 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeTo quantify the post-radiotherapy 2-[(18)F]-fluoro-2-deoxyglucose (FDG) pulmonary uptake dose-response in lung cancer patients and determine its relationship with radiation pneumonitis symptoms.Methods and materialsThe data from 24 patients treated for lung cancer with thoracic radiotherapy who received restaging PET/CT imaging between 4 and 12 weeks after radiotherapy completion were evaluated. Their radiation dose distribution was registered with the post-treatment restaging PET/CT. Using histogram analysis, the voxel average FDG-PET uptake vs. radiation dose was obtained for each case and linear regression was performed. The resulting slope, the pulmonary metabolic radiation response (PMRR), was used to characterize the dose-response. The Common Toxicity Criteria version 3 was used to score clinical pulmonary toxicity symptoms. Receiver operating characteristic (ROC) curves were used to determine the level of FDG uptake vs. dose, MLD, V(5), V(10), V(20), and V(30) that can best predict symptomatic and asymptomatic patients.ResultsThe median time between radiotherapy completion and FDG-PET imaging was 59 days (range, 26-70 days). The median of the mean SUV from lung that received 0-5 Gy was 1.00 (range, 0.37-1.48), 5-10 Gy was 1.01 (range, 0.37-1.77), 10-20 Gy was 1.04 (0.42-1.53), and >20 Gy was 1.29 (range, 0.41-8.01). Using the dose range of 0 Gy to the maximum dose minus 10 Gy, hierarchical linear regression model of the radiation dose and normalized FDG uptake per case found an adequate fit with the linear model. Pneumonitis scores were: Grade 0 for 13, Grade 1 for 5, Grade 2 for 6, and Grade 3, 4 or 5 for none. Using a PMRR threshold of 0.017 yields an associated true positive rate of 0.67 and false positive rate of 0.15 with average error of 30%. A V(5) threshold of 57.6 gives an associated true positive rate of 0.67 and false positive rate of 0.05 with a 20% average error.ConclusionThe metabolic radiation pneumonitis dose-response was evaluated from post-treatment FDG-PET/CT imaging. Statistical modeling found a linear relationship. The FDG uptake dose-response and V(5) correlated with symptomatic radiation pneumonitis.
| S-EPMC3626502 | biostudies-literature
Project description:External beam radiation therapy is a standard form of treatment for numerous cancers. Despite this, there are no approved methods to account for patient specific radiation sensitivity. In this report, Raman spectroscopy (RS) was used to identify radiation-induced biochemical changes in human non-small cell lung cancer xenografts. Chemometric analysis revealed unique radiation-related Raman signatures that were specific to nucleic acid, lipid, protein and carbohydrate spectral features. Among these changes was a dramatic shift in the accumulation of glycogen spectral bands for doses of 5 or 15 Gy when compared to unirradiated tumours. When spatial mapping was applied in this analysis there was considerable variability as we found substantial intra- and inter-tumour heterogeneity in the distribution of glycogen and other RS spectral features. Collectively, these data provide unique insight into the biochemical response of tumours, irradiated in vivo, and demonstrate the utility of RS for detecting distinct radiobiological responses in human tumour xenografts.
| S-EPMC4756358 | biostudies-literature
Project description:PurposeThis study aimed to investigate the heritability of corneal parameters obtained by Pentacam in nuclear families with keratoconus (KC).MethodsA total of 82 patients with KC and their biological parents (n = 164) were recruited in the current study. All subjects underwent corneal tomography with Pentacam. Family units were analyzed to calculate the heritability of corneal parameters by linear mixed effects model using the R statistical software.ResultsThe pachymetry at apex, pupil, and thinnest point were all significantly heritable at 43.26%, 42.63%, and 43.09%, respectively. The heritability of flat meridian keratometry, steep meridian keratometry, and mean keratometry in the anterior surface were 10.36%, 9.05%, and 10.21%, respectively, and that of flat meridian keratometry, steep meridian keratometry, and mean keratometry in the posterior surface were 8.44%, 9.67%, and 9.06%, respectively. The posterior radius of curvature had higher heritability in comparison with anterior radius of curvature (19.16% vs. 14.37%). Moreover, among combined topometric indices, the heritability of index of vertical asymmetry was the highest (19.49%), and that of central keratoconus index was the lowest (6.64%).ConclusionsThe present study demonstrated a substantial heritability of corneal parameters in nuclear families with KC. The pachymetric indices are heritable and may be suitable as KC endophenotypes, suggesting a necessity to discover the genes associated with corneal thickness in KC.Translational relevanceThe pachymetric indices are heritable and may be suitable as KC endophenotypes, indicating that the pachymetric indices might be a corneal characteristic to predict the occurrence of KC.
| S-EPMC9296886 | biostudies-literature
Project description:Radiation-induced esophagitis is the most common local acute toxicity of radiotherapy (RT) delivered for the curative or palliative intent treatment of lung cancer. Although concurrent chemotherapy and higher RT dose are associated with increased esophagitis risk, advancements in RT techniques as well as adherence to esophageal dosimetric constraints may reduce the incidence and severity. Mild acute esophagitis symptoms are generally self-limited, and supportive management options include analgesics, acid suppression, diet modification, treatment for candidiasis, and maintenance of adequate nutrition. Esophageal stricture is the most common late sequela from esophageal irradiation and can be addressed with endoscopic dilatation. Approaches to prevent or mitigate these toxicities are also discussed.
| S-EPMC5310706 | biostudies-other
Project description:BACKGROUND:Leukocyte telomere length (LTL), an indicator of aging, is influenced by both genetic and environmental factors; however, its heritability is unknown. We determined heritability and inheritance patterns of telomere length across three generations of families. METHODS:We analyzed 287 individuals from three generations of 41 Korean families, including newborns, parents, and grandparents. LTL (the ratio of telomere repeat copy number to single gene copy number) was measured by quantitative real-time PCR. We estimated heritability using the SOLAR software maximum-likelihood variance component methods and a pedigree dataset. With adjustment for age and length of marriage, Pearson's partial correlation was performed for spousal pairs. RESULTS:Heritability of LTL was high in all participants (h2?=?0.64). There were no significant differences in correlation coefficients of telomere length between paternal and maternal lines. There was a positive LTL correlation in grandfather-grandmother pairs (r?=?0.25, p?=?0.03) but not in father-mother pairs. After adjusting for age and length of marriage, the relationship between telomere lengths in grandfathers and grandmothers disappeared. There were inverse correlations between spousal rank differences of telomere length and length of marriage. CONCLUSIONS:LTL is highly heritable without a sex-specific inheritance pattern and may be influenced by a shared environment.
| S-EPMC7199797 | biostudies-literature
Project description:AimsThe aim of this study was to investigate the heritability as well as genetic and environmental correlations of left ventricular (LV) structural and functional traits in complex pedigrees of a Caucasian population.Methods and resultsWe randomly recruited 459 white European subjects from 52 families (50% women; mean age 45 years). LV structure was measured by M-mode and 2D echocardiography and LV function was measured by conventional Doppler and tissue Doppler imaging (TDI). Other measurements included blood pressure, anthropometric, and biochemical measurements. We estimated the heritability of LV traits while adjusting for covariables, including sex, age, body height and weight, systolic and diastolic blood pressures, and heart rate. With full adjustment, heritability of LV mass was 0.23 (P= 0.025). The TDI-derived mitral annular velocities Ea and Aa showed moderate heritability (h(2)= 0.36 and 0.53, respectively), whereas the mitral inflow A peak had weak heritability (h(2) = 0.25) and the E peak was not heritable (h(2) = 0.11). We partitioned the total phenotypic correlation when it reached significance, into a genetic and an environmental component. The genetic correlations were 0.61 between the E and Ea peaks and 0.90 between the A and Aa peaks.ConclusionOur study demonstrated moderate heritability for LV mass as well as the mitral annular Ea and Aa peaks. We also found significant genetic correlations between the E and Ea peaks and between the A and Aa peaks. Our current findings support the ongoing research to map and detect genetic variants that contribute to the variation in LV mass and other LV structural and functional phenotypes.
| S-EPMC3106286 | biostudies-literature
Project description:BackgroundA previous study suggested that intracranial aneurysms are more likely to occur in the same arterial territory within families. We aimed to replicate this analysis in independent families and in a sample limited to intracranial aneurysms that ruptured.MethodsAmong families with ≥2 first-degree relatives with intracranial aneurysms, we randomly matched index families to comparison families, and compared concordance in intracranial aneurysm territory between index and comparison families using a conditional logistic events/trials model. We analyzed three European cohorts separately, and pooled the results with those of the Familial Intracranial Aneurysm study by performing an inverse variance fixed effects meta-analysis. The main analysis included both unruptured and ruptured intracranial aneurysms, and a secondary analysis only ruptured intracranial aneurysms.ResultsAmong 70 Dutch, 142 Finnish, and 34 French families, concordance regarding intracranial aneurysm territory was higher within families than between families, although not statistically significant. Meta-analysis revealed higher concordance in territory within families overall (odds ratio [OR] 1.7, 95%CI 1.3-2.2) and for each separate territory except the anterior cerebral artery. In the analysis of ruptured intracranial aneurysms, overall territory concordance was higher within families than between families (OR 1.8; 95%CI 1.1-2.7) but the territory-specific analysis showed statistical significance only for the internal carotid artery territory.ConclusionsWe confirmed that familial intracranial aneurysms are more likely to occur in the same arterial territory within families. Moreover, we found that ruptured aneurysms were also more likely to occur in the same arterial territory within families.
| S-EPMC7398535 | biostudies-literature
Project description:BackgroundIntracranial aneurysms more often occur in the same arterial territory within families. Several aneurysm locations are associated with specific circle of Willis variations. We investigated whether the same circle of Willis variations are more likely to occur in first-degree relatives than in unrelated individuals.MethodsWe assessed four circle of Willis variations (classical, A1-asymmetry, incomplete posterior communicating artery and fetal circulation) in two independent groups of families with familial aneurysms and ≥2 first-degree relatives with circle of Willis imaging on MRA/CTA. In each (index) family we determined the proportion of first-degree relatives with the same circle of Willis variation as the proband and compared it to the proportion of first-degree relatives of a randomly selected unrelated (comparison) family who had the same circle of Willis variation as the index family's proband. Concordance in index families and comparison families was compared with a conditional logistic events/trials model. The analysis was simulated 1001 times; we report the median concordances, odds ratios (ORs), and 95% confidence intervals (95%CI). The groups were analysed separately and together by meta-analysis.ResultsWe found a higher overall concordance in circle of Willis configuration in index families than in comparison families (meta-analysis, 244 families: OR 2.2, 95%CI 1.6-3.0) mostly attributable to a higher concordance in incomplete posterior communicating artery (meta-analysis: OR 2.8, 95%CI 1.8-4.3). No association was found for the other three circle of Willis variations.ConclusionsIn two independent groups of families with familial aneurysms, the incomplete PcomA variation occurred more often within than between families suggesting heritability of this circle of Willis variation. Further studies should investigate genetic variants associated with circle of Willis formation.
| S-EPMC5788367 | biostudies-literature
Project description:The aim of this study is to identify clinically relevant image feature (IF) changes during chemoradiation and evaluate their efficacy in predicting treatment response. Patients with non-small-cell lung cancer (NSCLC) were enrolled in two prospective trials (STRIPE, PET-Plan). We evaluated 48 patients who underwent static (3D) and retrospectively-respiratory-gated 4D PET/CT scans before treatment and a 3D scan during or after treatment. Our proposed method rejects IF changes due to intrinsic variability. The IF variability observed across 4D PET is employed as a patient individualized normalization factor to emphasize statistically relevant IF changes during treatment. Predictions of overall survival (OS), local recurrence (LR) and distant metastasis (DM) were evaluated. From 135 IFs, only 17 satisfied the required criteria of being normally distributed across 4D PET and robust between 3D and 4D images. Changes during treatment in the area-under-the-curve of the cumulative standard-uptake-value histogram (δAUCCSH) within primary tumor discriminated (AUC = 0.87, Specificity = 0.78) patients with and without LR. The resulted prognostic model was validated with a different segmentation method (AUC = 0.83) and in a different patient cohort (AUC = 0.63). The quantification of tumor FDG heterogeneity by δAUCCSH during chemoradiation correlated with the incidence of local recurrence and might be recommended for monitoring treatment response in patients with NSCLC.
| S-EPMC7919471 | biostudies-literature
Project description:Numerous studies have implicated changes in the Y chromosome in male cancers, yet few have investigated the biological importance of Y chromosome noncoding RNA. Here we identify a group of Y chromosome-expressed long noncoding RNA (lncRNA) that are involved in male non-small cell lung cancer (NSCLC) radiation sensitivity. Radiosensitive male NSCLC cell lines demonstrated a dose-dependent induction of linc-SPRY3-2/3/4 following irradiation, which was not observed in radioresistant male NSCLC cell lines. Cytogenetics revealed the loss of chromosome Y (LOY) in the radioresistant male NSCLC cell lines. Gain- and loss-of-function experiments indicated that linc-SPRY3-2/3/4 transcripts affect cell viability and apoptosis. Computational prediction of RNA binding proteins (RBP) motifs and UV-cross-linking and immunoprecipitation (CLIP) assays identified IGF2BP3, an RBP involved in mRNA stability, as a binding partner for linc-SPRY3-2/3/4 RNA. The presence of linc-SPRY3-2/3/4 reduced the half-life of known IGF2BP3 binding mRNA, such as the antiapoptotic HMGA2 mRNA, as well as the oncogenic c-MYC mRNA. Assessment of Y chromosome in NSCLC tissue microarrays and expression of linc-SPRY3-2/3/4 in NSCLC RNA-seq and microarray data revealed a negative correlation between the loss of the Y chromosome or linc-SPRY3-2/3/4 and overall survival. Thus, linc-SPRY3-2/3/4 expression and LOY could represent an important marker of radiotherapy in NSCLC. SIGNIFICANCE: This study describes previously unknown Y chromosome-expressed lncRNA regulators of radiation response in male NSCLC and show a correlation between loss of chromosome Y and radioresistance. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/19/4046/F1.large.jpg.
| S-EPMC7541653 | biostudies-literature