Issues in Interpreting Epidemiologic Studies of Populations Exposed to Low-Dose, High-Energy Photon Radiation.
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ABSTRACT:
SUBMITTER: Gilbert ES
PROVIDER: S-EPMC7355296 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Rapid innovations in radiation therapy techniques have resulted in an urgent need for risk projection models for second cancer risks from high-dose radiation exposure, because direct observation of the late effects of newer treatments will require patient follow-up for a decade or more. However, the patterns of cancer risk after fractionated high-dose radiation are much less well understood than those after lower-dose exposures (0.1-5 Gy). In particular, there is uncertainty about the shape of the dose-response curve at high doses and about the magnitude of the second cancer risk per unit dose. We reviewed the available evidence from epidemiologic studies of second solid cancers in organs that received high-dose exposure (>5 Gy) from radiation therapy where dose-response curves were estimated from individual organ-specific doses. We included 28 eligible studies with 3434 second cancer patients across 11 second solid cancers. Overall, there was little evidence that the dose-response curve was nonlinear in the direction of a downturn in risk, even at organ doses of ?60 Gy. Thyroid cancer was the only exception, with evidence of a downturn after 20 Gy. Generally the excess relative risk per Gray, taking account of age and sex, was 5 to 10 times lower than the risk from acute exposures of <2 Gy among the Japanese atomic bomb survivors. However, the magnitude of the reduction in risk varied according to the second cancer. The results of our review provide insights into radiation carcinogenesis from fractionated high-dose exposures and are generally consistent with current theoretical models. The results can be used to refine the development of second solid cancer risk projection models for novel radiation therapy techniques.
| S-EPMC3816386 | biostudies-literature
Project description:Ionizing radiation, such as that emitted by uranium, may cause mutations and consequently lead to neoplasia in human cells. The TP53 gene acts to maintain genomic integrity and constitutes an important biomarker of susceptibility. The present study investigated the main alterations observed in exons 4, 5, 6, 7, and 8 of the TP53 gene and adjacent introns in Amazonian populations exposed to radioactivity. Samples were collected from 163 individuals. Occurrence of the following alterations was observed: (i) a missense exchange in exon 4 (Arg72Pro); (ii) 2 synonymous exchanges, 1 in exon 5 (His179His), and another in exon 6 (Arg213Arg); (iii) 4 intronic exchanges, 3 in intron 7 (C → T at position 13.436; C → T at position 13.491; T → G at position 13.511) and 1 in intron 8 (T → G at position 13.958). Alteration of codon 72 was found to be an important risk factor for cancer development (P = 0.024; OR = 6.48; CI: 1.29-32.64) when adjusted for age and smoking. Thus, TP53 gene may be an important biomarker for carcinogenesis susceptibility in human populations exposed to ionizing radiation.
| S-EPMC3613089 | biostudies-literature
Project description: Not available
| S-EPMC8530151 | biostudies-literature
Project description:Meta-analysis approaches can be used to assess the human risks due to exposure to environmental chemicals when there are numerous high-quality epidemiologic studies of priority outcomes in a database. However, methodological issues related to how different studies report effect measures and incorporate exposure into their analyses arise that complicate the pooled analysis of multiple studies. As such, there are "pre-analysis" steps that are often necessary to prepare summary data reported in epidemiologic studies for dose-response analysis. This paper uses epidemiologic studies of arsenic-induced health effects as a case example and addresses the issues surrounding the estimation of mean doses from censored dose- or exposure-intervals reported in the literature (e.g., estimation of mean doses from high exposures that are only reported as an open-ended interval), calculation of a common dose metric for use in a dose-response meta-analysis (one that takes into consideration inter-individual variability), and calculation of response "effective counts" that inherently account for confounders. The methods herein may be generalizable to 1) the analysis of other environmental contaminants with a suitable database of epidemiologic studies, and 2) any meta-analytic approach used to pool information across studies. A second companion paper detailing the use of "pre-analyzed" data in a hierarchical Bayesian dose-response model and techniques for extrapolating risks to target populations follows.
| S-EPMC7534797 | biostudies-literature
Project description:In epidemiological investigations of cancer risk from occupational exposure, it is important to obtain an organ-specific dose for each cohort member for accurate risk analysis. To date, dose conversion coefficients, which convert physical dose measurement to organ dose, are only available for individuals with reference body size, which can differentially bias the estimated organ dose depending on the body mass index of cohort members. In the current study, we calculated the organ dose coefficients applicable to adult males and females with various body weights by using the Monte Carlo radiation transport technique combined with a library of body size-dependent hybrid computational phantoms exposed in six idealised irradiation geometries. We adapted the eight adult male phantoms, 175 cm tall with weights of 60, 70, 80, 90, 100, 110, 120 and 130 kg, and the nine adult female phantoms, 165 cm tall with weights of 50, 60, 70, 80, 90, 100, 110, 120 and 130 kg. The radiation transport was simulated using MCNPX 2.7 Monte Carlo code. Phantoms were irradiated by external photon fields in anterior posterior (AP), posterior-anterior, right and left lateral, rotational, and isotropic geometries. The results showed that the 60 kg adult male phantom shows 1.33-, 1.43-, 1.44- and 1.52-fold greater dose coefficients for the lungs, heart, stomach, and liver, respectively, than the 120 kg adult male phantom at 0.1 MeV in AP geometry. We derived exponential correlation between organ dose coefficients and body weight to facilitate calculation of organ dose coefficients for a given weight. The comprehensive organ dose coefficients and exponential regression model can be used to estimate more accurate organ dose for individuals of the two genders with various body weights exposed to external photon radiation.
| S-EPMC6376489 | biostudies-literature
Project description:In the current global scenario there is always a possibility that a terrorist group might acquire material to produce a nuclear device. In the likelihood of a detonation of an improvised nuclear device (IND) the prompt radiation would consist of both photons (gamma rays) and neutrons. As neutrons generally have a high Relative Biological Effectiveness (RBE) for most physiological endpoints, it is important to understand the impact that neutrons would have on the biodosimetry methods that are being developed for medical triage purposes. We have previously reported transcriptomic response in human and mouse blood to neutron exposure and determined its RBE compared to photons for gene induction. In this report, we studied the effect of mixed neutron-photon radiation on gene expression in human peripheral blood in order to mimic an IND type radiation observed increase in number as well as expression level of genes with increasing percentage of neutron in mixed exposures which peaked at 25% neutron exposure which was maximum neutron percentage used for the study. We identified 156 genes that responded significantly to all the neutron-photon mixed exposures. These genes were found to be mainly involved in p53 signaling and DNA damage response. The 25% neutron exposure also showed maximum enrichment of known neutron associated gene ontology terms reported in the previous studies. Analysis of upstream regulators of gene expression showed strong activation of TP53, SLC29A1, PDCD1 and suppression of ANLN, AURK and ANXA2 across all exposures. While AGT was exclusively activated by neutron specific exposures. We confirmed the expression of genes which showed increased expression as a function of increased neutron percentage using quantitative real-time RT-PCR which matched with the microarray data. Thus, the data in this current study clearly indicates that gene expression can be used to estimate the percentage of the neutron component in mixed neutron-photon exposures.
2020-09-02 | GSE113611 | GEO
Project description:BackgroundPrevious epidemiologic studies have reported inconsistent results between parity and pancreatic cancer (PC) risk. To our knowledge, a comprehensive and quantitative assessment of this association has not been conducted.MethodsRelevant published studies of parity and PC were identified using MEDLINE (PubMed) and Web of Science databases until November 2013. Two authors (H-BG and LW) independently assessed eligibility and extracted data. Eleven prospective and 11 case-control studies reported relative risk (RR) estimates and 95% confidence intervals (CIs) of PC associated with parity. Fixed- and random-effects models were used to estimate the summary RR depending on the heterogeneity of effects.ResultsThe summary RR for PC comparing the highest versus lowest parity was 0.86 (95% CI: 0.73-1.02; Q = 50.49, P<0.001, I2 = 58.4%). Significant inverse associations were also observed in the studies that adjusted for cigarette smoking (RR = 0.81; 95% CI: 0.68-0.98), Type 2 diabetes mellitus (RR = 0.83; 95% CI: 0.75-0.93), and those that included all confounders or important risk factors (RR = 0.85; 95% CI: 0.76-0.96). Additionally, in the dose-response analysis, the summary RR for per one live birth was 0.97 (95% CI: 0.94-1.01; Q = 62.83, P<0.001, I2 = 69.8%), which also indicated a borderline statistically significant inverse effect of parity on PC risk. No evidence of publication bias and significant heterogeneity between subgroups were detected by meta-regression analyses.ConclusionIn summary, these findings suggest that higher parity is associated with a decreased risk of PC. Future large consortia or pooled studies are warranted to fully adjust for potential confounders to confirm this association.
| S-EPMC3962437 | biostudies-literature
Project description:Gold nanoparticles (GNPs) emerged as promising antitumor radiosensitizers. However, the complex dependence of GNPs radiosensitization on the irradiation conditions remains unclear. In the present study, we investigated the impacts of the dose rate and photon energy on damage of the pBR322 plasmid DNA exposed to X-rays in the presence of 12 nm, 15 nm, 21 nm, and 26 nm GNPs. The greatest radiosensitization was observed for 26 nm GNPs. The sensitizer enhancement ratio (SER) 2.74 ± 0.61 was observed at 200 kVp with 2.4 mg/mL GNPs. Reduction of X-ray tube voltage to 150 and 100 kVp led to a smaller effect. We demonstrate for the first time that the change of the dose rate differentially influences on radiosensitization by GNPs of various sizes. For 12 nm, an increase in the dose rate from 0.2 to 2.1 Gy/min led to a ~1.13-fold increase in radiosensitization. No differences in the effect of 15 nm GNPs was found within the 0.85-2.1 Gy/min range. For 21 nm and 26 nm GNPs, an enhanced radiosensitization was observed along with the decreased dose rate from 2.1 to 0.2 Gy/min. Thus, GNPs are an effective tool for increasing the efficacy of orthovoltage X-ray exposure. However, careful selection of irradiation conditions is a key prerequisite for optimal radiosensitization efficacy.
| S-EPMC7279506 | biostudies-literature
Project description:BackgroundRadiation exposure due to the detonation of an improvised nuclear device remains a major security concern. Radiation from such a device involves a combination of photons and neutrons. Although photons will make the greater contribution to the total dose, neutrons will certainly have an impact on the severity of the exposure as they have high relative biological effectiveness.ResultsWe investigated the gene expression signatures in the blood of mice exposed to 3 Gy x-rays, 0.75 Gy of neutrons, or to mixed field photon/neutron with the neutron fraction contributing 5, 15%, or 25% of a total 3 Gy radiation dose. Gene ontology and pathway analysis revealed that genes involved in protein ubiquitination pathways were significantly overrepresented in all radiation doses and qualities. On the other hand, eukaryotic initiation factor 2 (EIF2) signaling pathway was identified as one of the top 10 ranked canonical pathways in neutron, but not pure x-ray, exposures. In addition, the related mTOR and regulation of EIF4/p70S6K pathways were also significantly underrepresented in the exposures with a neutron component, but not in x-ray radiation. The majority of the changed genes in these pathways belonged to the ribosome biogenesis and translation machinery and included several translation initiation factors (e.g. Eif2ak4, Eif3f), as well as 40S and 60S ribosomal subunits (e.g. Rsp19, Rpl19, Rpl27). Many of the differentially downregulated ribosomal genes (e.g. RPS19, RPS28) have been causally associated with human bone marrow failure syndromes and hematologic malignancies. We also observed downregulation of transfer RNA processes, in the neutron-only exposure (p < 0.005). Ingenuity Pathway Analysis (p < 0.05) of differentially expressed genes predicted significantly suppressed activity of the upstream regulators c-Myc and Mycn, transcription factors known to control ribosome biogenesis.ConclusionsWe describe the gene expression profile of mouse blood following exposure to mixed field neutron/photon irradiation. We have discovered that pathways related to protein translation are significantly underrepresented in the exposures containing a neutron component. Our results highlight the significance of neutron exposures that even the smallest percentage can have profound biological effects that will affect medical management and treatment decisions in case of a radiological emergency.
| S-EPMC6027792 | biostudies-literature
Project description:In a recent article in the American Journal of Epidemiology by Mendez et al. (Am J Epidemiol. 2011;173(4):448-458), the use of alternative approaches to the exclusion of implausible energy intakes led to significantly different cross-sectional associations between diet and body mass index (BMI), whereas the use of a simpler recommended criteria (<500 and >3,500 kcal/day) yielded no meaningful change. However, these findings might have been due to exclusions made based on weight, a primary determinant of BMI. Using data from 52,110 women in the Nurses' Health Study (1990), we reproduced the cross-sectional findings of Mendez et al. and compared the results from the recommended method with those from 2 weight-dependent alternative methods (the Goldberg method and predicted total energy expenditure method). The same 3 exclusion criteria were then used to examine dietary variables prospectively in relation to change in BMI, which is not a direct function of attained weight. We found similar associations using the 3 methods. In a separate cross-sectional analysis using biomarkers of dietary factors, we found similar correlations for intakes of fatty acids (n = 439) and carotenoids and retinol (n = 1,293) using the 3 methods for exclusions. These results do not support the general conclusion that use of exclusion criteria based on the alternative methods might confer an advantage over the recommended exclusion method.
| S-EPMC4325679 | biostudies-literature