The epidemiology of lung cancer following radiation exposure.
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ABSTRACT:
SUBMITTER: Zablotska LB
PROVIDER: S-EPMC9943789 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
Publications
The epidemiology of lung cancer following radiation exposure.
Zablotska Lydia B LB Richardson David B DB Golden Ashley A Pasqual Elisa E Smith Brian B Rage Estelle E Demers Paul A PA Do Minh M Fenske Nora N Deffner Veronika V Kreuzer Michaela M Samet Jonathan J Bertke Stephen S Kelly-Reif Kaitlin K Schubauer-Berigan Mary K MK Tomasek Ladislav L Wiggins Charles C Laurier Dominque D Apostoaei Iulian I Thomas Brian A BA Simon Steven L SL Hoffman F Owen FO Boice John D JD Dauer Lawrence T LT Howard Sara C SC Cohen Sarah S SS Mumma Michael T MT Ellis Elizabeth D ED Eckerman Keith F KF Leggett Rich W RW Pawel David J DJ
International journal of radiation biology 20220822 3
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Project description:Ionizing radiation is a known mutagen and an established breast carcinogen. The ATM gene is a key regulator of cellular responses to the DNA damage induced by ionizing radiation. We investigated whether genetic variants in ATM play a clinically significant role in radiation-induced contralateral breast cancer in women.The Women's Environmental, Cancer, and Radiation Epidemiology Study is an international population-based case-control study nested within a cohort of 52,536 survivors of unilateral breast cancer diagnosed between 1985 and 2000. The 708 case subjects were women with contralateral breast cancer, and the 1397 control subjects were women with unilateral breast cancer matched to the case subjects on age, follow-up time, registry reporting region, and race and/or ethnicity. All women were interviewed and underwent full mutation screening of the entire ATM gene. Complete medical treatment history information was collected, and for all women who received radiotherapy, the radiation dose to the contralateral breast was reconstructed using radiotherapy records and radiation measurements. Rate ratios (RRs) and corresponding 95% confidence intervals (CIs) were estimated by using multivariable conditional logistic regression. All P values are two-sided.Among women who carried a rare ATM missense variant (ie, one carried by <1% of the study participants) that was predicted to be deleterious, those who were exposed to radiation (mean radiation exposure = 1.2 Gy, SD = 0.7) had a statistically significantly higher risk of contralateral breast cancer compared with unexposed women who carried the wild-type genotype (0.01-0.99 Gy: RR = 2.8, 95% CI = 1.2 to 6.5; > or =1.0 Gy: RR = 3.3, 95% CI = 1.4 to 8.0) or compared with unexposed women who carried the same predicted deleterious missense variant (0.01-0.99 Gy: RR = 5.3, 95% CI = 1.6 to 17.3; > or =1.0 Gy: RR = 5.8, 95% CI = 1.8 to 19.0; P(trend) = .044).Women who carry rare deleterious ATM missense variants and who are treated with radiation may have an elevated risk of developing contralateral breast cancer. However, the rarity of these deleterious missense variants in human populations implies that ATM mutations could account for only a small portion of second primary breast cancers.
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Project description:Mortality and cancer incidence were studied in the National Registry for Radiation Workers in, relative to earlier analyses, an enlarged cohort of 174 541 persons, with longer follow-up (to 2001) and, for the first time, cancer registration data. SMRs for all causes and all malignant neoplasms were 81 and 84 respectively, demonstrating a 'healthy worker effect'. Within the cohort, mortality and incidence from both leukaemia excluding CLL and the grouping of all malignant neoplasms excluding leukaemia increased to a statistically significant extent with increasing radiation dose. Estimates of the trend in risk with dose were similar to those for the Japanese A-bomb survivors, with 90% confidence intervals that excluded both risks more than 2-3 times greater than the A-bomb values and no raised risk. Some evidence of an increasing trend with dose in mortality from all circulatory diseases may, at least partly, be due to confounding by smoking. This analysis provides the most precise estimates to date of mortality and cancer risks following occupational radiation exposure and strengthens the evidence for raised risks from these exposures. The cancer risk estimates are consistent with values used to set radiation protection standards.
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Project description:The vascular system is sensitive to radiation injury, and vascular damage is believed to play a key role in delayed tissue injury such as pulmonary fibrosis. However, the response of endothelial cells to radiation is not completely understood. We examined the response of primary human lung microvascular endothelial cells (HLMVEC) to 10 Gy (1.15 Gy/min) X-irradiation. HLMVEC underwent senescence (80-85%) with no significant necrosis or apoptosis. Targeted RT-qPCR showed increased expression of genes CDKN1A and MDM2 (10-120 min). Western blotting showed upregulation of p2/waf1, MDM2, ATM, and Akt phosphorylation (15 min-72 h). Low levels of apoptosis at 24-72 h were identified using nuclear morphology. To identify novel pathway regulation, RNA-seq was performed on mRNA using time points from 2 to 24 h post-irradiation. Gene ontology and pathway analysis revealed increased cell cycle inhibition, DNA damage response, pro- and anti- apoptosis, and pro-senescence gene expression. Based on published literature on inflammation and endothelial-to-mesenchymal transition (EndMT) pathway genes, we identified increased expression of pro-inflammatory genes and EndMT-associated genes by 24 h. Together our data reveal a time course of integrated gene expression and protein activation leading from early DNA damage response and cell cycle arrest to senescence, pro-inflammatory gene expression, and endothelial-to-mesenchymal transition.
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Project description:The radiation fields in space define tangible risks to the health of astronauts, and significant work in rodent models has clearly shown a variety of exposure paradigms to compromise central nervous system (CNS) functionality. Despite our current knowledge, sex differences regarding the risks of space radiation exposure on cognitive function remain poorly understood, which is potentially problematic given that 30% of astronauts are women. While work from us and others have demonstrated pronounced cognitive decrements in male mice exposed to charged particle irradiation, here we show that female mice exhibit significant resistance to adverse neurocognitive effects of space radiation. The present findings indicate that male mice exposed to low doses (≤30 cGy) of energetic (400 MeV/n) helium ions (4He) show significantly higher levels of neuroinflammation and more extensive cognitive deficits than females. Twelve weeks following 4He ion exposure, irradiated male mice demonstrated significant deficits in object and place recognition memory accompanied by activation of microglia, marked upregulation of hippocampal Toll-like receptor 4 (TLR4), and increased expression of the pro-inflammatory marker high mobility group box 1 protein (HMGB1). Additionally, we determined that exposure to 4He ions caused a significant decline in the number of dendritic branch points and total dendritic length along with the hippocampus neurons in female mice. Interestingly, only male mice showed a significant decline of dendritic spine density following irradiation. These data indicate that fundamental differences in inflammatory cascades between male and female mice may drive divergent CNS radiation responses that differentially impact the structural plasticity of neurons and neurocognitive outcomes following cosmic radiation exposure.
| S-EPMC7525092 | biostudies-literature
Project description:BackgroundCoronary catheterization (CC) procedure inevitably exposes patients with cardiovascular disease (CVD) to radiation, while cumulative radiation exposure may lead to higher risk of cancer.MethodsThis multi-center, retrospective study was based on the CC procedure in Cardiorenal ImprovemeNt II cohort (CIN-II, NCT05050877) among five regional central tertiary teaching hospitals in China between 2007 and 2020. Patients without known cancer were stratified according to the times they received CC procedure. Baseline information from their last CC procedure was analyzed. Cox regression and Fine-Gray competing risk models were used to assess the relationship between cumulative radiation exposure from CC procedures and cancer-specific, all-cause and cardiovascular mortality.ResultsOf 136,495 hospitalized survivors without cancer at baseline (mean age: 62.3 ± 11.1 years, 30.9% female), 116,992 patients (85.7%) underwent CC procedure once, 15,184 patients (11.1%) on twice, and 4,319 patients (3.2%) underwent CC procedure more than three times. During the median follow-up of 4.7 years (IQR: 2.5 to 7.4), totally 18,656 patients (13.7%) died after discharge, of which 617 (0.5%) died of lung cancer. Compared with the patients who underwent CC procedure once, the risk of lung cancer mortality increased significantly with the increase of the number of CC procedure (CC 2 times vs. 1 time: HR 1.42, 95% CI 1.13 to 1.78, P < 0.001; CC ≥ 3 times vs. 1 time: HR 1.64, 95%CI 1.13 to 2.39, P < 0.05). Similar results were observed in all-cause mortality and cardiovascular mortality, but not in other cancer-specific mortality.ConclusionsOur data suggest that substantial proportion of CVD patients are exposed to multiple high levels of low-dose ionizing radiation from CC procedure, which is associated with an increased risk of cancer mortality in this population.Trial registrationClinicalTrials.gov: NCT05050877; URL: http://www.Clinicaltrialsgov ; 21/09/2021.
| S-EPMC10426196 | biostudies-literature
Project description:IntroductionRadiation induced lymphopenia (RIL) deteriorate survival and diminishes the benefit of immune checkpoint inhibitors in combined treatment of lung cancer. Given the inconsistent data across various studies on the predictors of RIL, we aim to methodically elucidate these predictors and formulate a practical guide for clinicians.MethodsWe conducted observational cohort study in four tertiary cancer centers. Patients with non-small cell lung cancer and small cell lung cancer, without lymphopenia grade >1, who underwent standalone radiotherapy (RT) in minimum 15 fractions were eligible. Dose-volume parameters of structures and clinical factors were comprehensively analyzed using various predictors selection methods and statistical models (Linear Regressors, Elastic Net, Bayesian Regressors, Huber Regression, regression based on k-nearest neighbors, Gaussian Process Regressor, Decision Tree Regressor, Random Forest Regressor, eXtreme Gradient Boosting, Automated Machine Learning) and were ranked to predict lymphocytes count nadir (alc_nadir).ResultsTwo hundred thirty eight patients (stage I-3.4%, II-17.6%, III-75.2%, IV-3.8%) who underwent RT to median dose of 60 Gy were analyzed. Median alc_nadir was 0.68K/mm3. The 60 feature sets were evaluated in 600 models (RMSE 0.27-0.41K/mm³). The most important features were baseline lymphocyte count (alc_1), mean lung_dose, lung v05, lung v10, heart v05 and effective dose to immune cells (edic). In patients with alc_1 ≤ 2.005K/mm3, median alc_nadir predictions were 0.54K/mm3 for lung_v05p > 51.8% and 0.76K/mm3 for lung_v05p ≤ 51.8%. Lymphopenia was rare in patients with alc_1 > 2.005K/mm3.DiscussionRIL was most severe in patients with low early lymphocyte counts, primarily triggered by low RT doses in the heart and lungs.
| S-EPMC11324483 | biostudies-literature
Project description:This study was designed to identify molecular changes induced by radiation in mouse lung.
2014-08-21 | GSE60541 | GEO
Project description:This study was designed to identify molecular changes induced by radiation in mouse lung. Mouse left lung was irradiated with a single dose of radiation. Total RNA from the irradiated lung tissue was subject to single channnel microarray.
2014-08-21 | E-GEOD-60541 | biostudies-arrayexpress
Project description:ObjectivesThrough a survey on perception of lung cancer screening and accompanying medical radiation exposure in Korea, the present study was to investigate its current situations and evaluate various perception of physicians regarding it in order to propose measures for improvements.MethodsMedical specialists in national cancer screening institutions selected through stratified random sampling were subjected to face-to-face interview using a structured questionnaire. We investigated physicians' perception on effectiveness of lung cancer screening depending on screening modality, selection criteria for subjects of screening, types of equipment used to screen, and perception for seriousness of adverse effects following the test. In addition, odds ratios to underestimate risk of radiation exposure from screening were calculated through logistic regression analysis.ResultsEach response that chest X-ray is effective for lung cancer screening and that smoking history is not considered prior to screening recommendation accounted for more than 60% of respondents, suggesting the chance of unnecessary screening tests. Regarding adverse effects of lung cancer screening, about 85% of respondents replied that false positive, radiation exposure, and overdiagnosis could be ignored. About 70% of respondents underestimated radiation dose from lung cancer screening, and a low proportion of physicians informed patients of radiation exposure risk.ConclusionsIt was found that most physicians underestimated harms of lung cancer screening including radiation exposure and were lack of awareness regarding lung cancer screening. It should be noted that physicians need to have proper perceptions about screening recommendation and accompanying possible harms, for successful implementation of the screening program.
| S-EPMC6060336 | biostudies-literature
Project description:PurposeThe current study was undertaken to examine the trends in the lung cancer incidence, mortality, and survival after a diagnosis in Korea.Materials and methodsLung cancer incidence data according to the histologic type and mortality data were obtained from the Korea Central Cancer Registry and the Statistics Korea, respectively. The age-standardized incidence and mortality rates were calculated, and the Joinpoint model and age-period-cohort analyses were used to describe the trends in the rates. The 5-year relative survival rates of lung cancer were also calculated.ResultsAlthough the number of new lung cancer cases increased between 1999 and 2012, the age-standardized incidence rate decreased by 0.9% per year in men, whereas the incidence in women increased by 1.7% per year over the same time. Until 2010, the most common histologic type in men was squamous cell carcinoma, then adenocarcinoma prevailed thereafter. Since 1999, the most frequent histological type in women was adenocarcinoma. The lung cancer mortality started to decrease in 2002, with a more apparent decline for the younger age groups in both men and women. Overall, the 5-year relative survival rates have improved significantly from 11.2% for men and 14.7% for women among patients diagnosed between 1993 and 1997 to 19.3% for men and 28.2% for women among patients diagnosed between 2008 and 2012, respectively. An improvement in survival rate was observed for all major histology groups.ConclusionThe epidemiology of lung cancer in Korea has changed over a short time span, with decreasing mortality and improving survival rates. Further study is warranted to determine the cause of these changes.
| S-EPMC5512360 | biostudies-literature