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Age at exposure is a critical modifier of the risk of radiation-induced cancer. However, the effects of age on radiation-induced carcinogenesis remain poorly understood. In this study, we focused on tissue stem cells using Lgr5-eGFP-ires-CreERT2 mice to compare radiation-induced DNA damage responses between Lgr5+ and Lgr5- intestinal stem cells. Three-dimensional immunostaining analyses demonstrated that radiation induced apoptosis and the mitotic index more efficiently in adult Lgr5- stem cells than in adult Lgr5+ stem cells but not in infants, regardless of Lgr5 expression. Supporting this evidence, rapid and transient p53 activation occurred after irradiation in adult intestinal crypts but not in infants. RNA sequencing revealed greater variability in gene expression in adult Lgr5+ stem cells than in infant Lgr5+ stem cells after irradiation. Notably, the cell cycle and DNA repair pathways were more enriched in adult stem cells than in infant stem cells after irradiation. Our findings suggest that radiation-induced DNA damage responses in mouse intestinal crypts differ between infants and adults, potentially contributing to the age-dependent susceptibility to radiation carcinogenesis. [ABSTRACT FROM AUTHOR]

Radiation-induced secondary cancers relevant to proton therapy are still a main concern among cancer survivors. This study aims to determine the effects of age at exposure and treatment field size on radiation-induced secondary tumors following the proton therapy of lung cancer within out of field organs through the Monte Carlo (MC) simulation approach. A full MC model of ICRP-110 male phantom was simulated to calculate the absorbed dose corresponding to secondary radiations within distant organs from the tumor volume. Then, the risks of secondary malignancies were estimated by employing the recommended risk model by the Committee of Biological Effects of Ionizing Radiation (BEIR) for different treatment field sizes and various patient ages at exposure. The results revealed that by increasing the patient age from 25 to 45 years, lifetime attributable risk (LAR) values were decreased. Maximum and minimum mortality rates were obtained for the liver and thyroid at the fixed age of 25 years, respectively. Calculated risk values for most near organs to the tumor were higher than those for distant organs. Changing the aperture size from 5 × 5 cm2 to 8 × 10 cm2 resulted in LAR increments with maximum variations of 12.5% for the stomach and a rough variation of 1.12 times in LAR for all exposure ages. Our work on whole-body phantom addresses the impact of age at exposure and aperture size on LAR during the proton therapy of lung cancer. To minimize secondary cancer risks relevant to proton therapy of lung cancer, extra attention should be considered. [ABSTRACT FROM AUTHOR]

Cataract (opacification of the ocular lens) is a typical tissue reaction (deterministic effect) following ionizing radiation exposure, for which prevention dose limits have been recommended in the radiation protection system. Manifestations of radiation cataracts can vary among individuals, but such potential individual responses remain uncharacterized. Here we review relevant literature and discuss implications for radiation protection. This review assesses evidence for significant modification of radiation-induced cataractogenesis by age at exposure, sex and genetic factors based on current scientific literature. In addition to obvious physical factors (e.g. dose, dose rate, radiation quality, irradiation volume), potential factors modifying individual responses for radiation cataracts include sex, age and genetics, with comorbidity and coexposures also having important roles. There are indications and preliminary data identifying such potential modifiers of radiation cataract incidence or risk, although no firm conclusions can yet be drawn. Further studies and a consensus on the evidence are needed to gain deeper insights into factors determining individual responses regarding radiation cataracts and the implications for radiation protection. [ABSTRACT FROM AUTHOR]

One of the principal uncertainties when estimating population risk of late effects from epidemiological data is that few radiation-exposed cohorts have been followed up to extinction. Therefore, the relative risk model has often been used to estimate radiation-associated risk and to extrapolate risk to the end of life. Epidemiological studies provide evidence that children are generally at higher risk of cancer induction than adults for a given radiation dose. However, the strength of evidence varies by cancer site and questions remain about site-specific age at exposure patterns. For solid cancers, there is a large body of evidence that excess relative risk (ERR) diminishes with increasing age at exposure. This pattern of risk is observed in the Life Span Study (LSS) as well as in other radiation-exposed populations for overall solid cancer incidence and mortality and for most site-specific solid cancers. However, there are some disparities by endpoint in the degree of variation of ERR with exposure age, with some sites (e.g., colon, lung) in the LSS incidence data showing no variation, or even increasing ERR with increasing age at exposure. The pattern of variation of excess absolute risk (EAR) with age at exposure is often similar, with EAR for solid cancers or solid cancer mortality decreasing with increasing age at exposure in the LSS. We shall review the human data from the Japanese LSS cohort, and a variety of other epidemiological data sets, including a review of types of medical diagnostic exposures, also some radiobiological animal data, all bearing on the issue of variations of radiation late-effects risk with age at exposure and with attained age. The paper includes a summary of several oral presentations given in a Symposium on "Age effects on radiation response" as part of the 67th Annual Meeting of the Radiation Research Society, held virtually on 3–6 October 2021. [ABSTRACT FROM AUTHOR]

Abstract Background Michigan residents were directly exposed to endocrine-disrupting compounds, polybrominated biphenyl (PBB) and polychlorinated biphenyl (PCB). A growing body of evidence suggests that exposure to certain endocrine-disrupting compounds may affect thyroid function, especially in people exposed as children, but there are conflicting observations. In this study, we extend previous work by examining age of exposure’s effect on the relationship between PBB exposure and thyroid function in a large group of individuals exposed to PBB. Methods Linear regression models were used to test the association between serum measures of thyroid function (total thyroxine (T4), total triiodothyronine (T3), free T4, free T3, thyroid stimulating hormone (TSH), and free T3: free T4 ratio) and serum PBB and PCB levels in a cross-sectional analysis of 715 participants in the Michigan PBB Registry. Results Higher PBB levels were associated with many thyroid hormones measures, including higher free T3 (p = 0.002), lower free T4 (p = 0.01), and higher free T3: free T4 ratio (p = 0.0001). Higher PCB levels were associated with higher free T4 (p = 0.0002), and higher free T3: free T4 ratio (p = 0.002). Importantly, the association between PBB and thyroid hormones was dependent on age at exposure. Among people exposed before age 16 (N = 446), higher PBB exposure was associated with higher total T3 (p = 0.01) and free T3 (p = 0.0003), lower free T4 (p = 0.04), and higher free T3: free T4 ratio (p = 0.0001). No significant associations were found among participants who were exposed after age 16. No significant associations were found between TSH and PBB or PCB in any of the analyses conducted. Conclusions This suggests that both PBB and PCB are associated with thyroid function, particularly among those who were exposed as children or prenatally.

Purpose: Occupational exposure to combustion products rich in polycyclic aromatic hydrocarbons and particles is associated with an increased risk of lung cancer. This study aimed to evaluate whether the risk depended on the age at which the individuals were exposed. Methods: Data from 1042 lung cancer cases and 2364 frequency-matched population controls selected from all men aged 40-75 years residing in Stockholm County, Sweden, at any time between 1985 and 1990, included detailed questionnaire information on occupational, residential, and smoking history. Occupational exposures were assessed by an occupational hygienist, and exposure to air pollution from road traffic was estimated based on dispersion models. Results: We found that individuals exposed to combustion products in their twenties were at higher risk than those never exposed (adjusted OR = 1.46; 95 % CI 1.02, 2.10). The association was still evident after adjusting for a number of potential confounders, including lifetime cumulative exposure and latency. No clear association was found in those exposed at older ages. Conclusions: Exposure to combustion products at a young age was associated with elevated risk of lung cancer. Exposure-reduction programs should be aware of the susceptibility of the younger employees. [ABSTRACT FROM AUTHOR]

Purpose: Phenomenological risk models for radiation-induced cancer are frequently applied to estimate the risk of radiation-induced cancers at radiotherapy doses. Such models often include the effect modification, of the main risk to radiation dose response, by age at exposure and attained age. The aim of this paper is to compare the patterns in risk effect modification by age, between models obtained from the Japanese atomic-bomb (A-bomb) survivor data and models for cancer risks previously reported for radiotherapy patients. Patterns in risk effect modification by age from the epidemiological studies of radiotherapy patients were also used to refine and extend the risk effect modification by age obtained from the A-bomb survivor data, so that more universal models can be presented here. Methods: Simple log-linear and power functions of age for the risk effect modification applied in models of the A-bomb survivor data are compared to risks from epidemiological studies of second cancers after radiotherapy. These functions of age were also refined and fitted to radiotherapy risks. The resulting age models provide a refined and extended functional dependence of risk with age at exposure and attained age especially beyond 40 and 65 yr, respectively, and provide a better representation than the currently available simple age functions. Results: It was found that the A-bomb models predict risk similarly to the outcomes of testicular cancer survivors. The survivors of Hodgkin's disease show steeper variations of risk with both age at exposure and attained age. The extended models predict solid cancer risk increase as a function of age at exposure beyond 40 yr and the risk decrease as a function of attained age beyond 65 yr better than the simple models. Conclusions: The standard functions for risk effect modification by age, based on the A-bomb survivor data, predict second cancer risk in radiotherapy patients for ages at exposure prior to 40 yr and attained ages before 55 yr reasonably well. However, for larger ages, the refined and extended models can be applied to predict the risk as a function of age. [ABSTRACT FROM AUTHOR]

Abstract: The determination of critical windows of susceptibility to environmental chemical exposures and health has become a major public health focus. This study examined the association between early age at exposure to polybrominated biphenyls (PBBs) and subsequent birth weight and gestational length in offspring among females. The study population consisted of 1111 births that occurred among 560 women enrolled in the Michigan PBB Cohort from 1975 to 1994. Maternal age at exposure was categorized into three groups:<10 years (n=64), 11–16 years (n=149), and 17–42 years (n=347). Overall serum PBB levels ranged from 0 to 1490ppb, with a median of 2, 3, and 2ppb in the three age groups, respectively. Separate mixed-effects linear regression models were used to evaluate the effect of age at exposure (years) and initial PBB level (ppb) on birth weight (grams) and gestational age (weeks), controlling for gestational age (weeks) (in the model examining effects on birth weight), BMI (kg/m2) and serum PCB level at enrollment (ppb), maternal age and paternal education at delivery, parity, infant gender, interval between the initial serum test and date of delivery (years), and the trimester in which prenatal care was initiated. Relative to the oldest age group, age<10 years at exposure was the most important predictor of increased birth weight (estimated regression coefficient=225g, P=0.012). Infant birth weight increased approximately 16g for every 10ppb increase in serum PBBs (P=0.004). There was no association between initial PBB levels and gestational age, nor were initial serum PCB levels associated with either infant birth weight or gestational length. These results provide support for the hypothesis that early age at exposure may be an important determinant in subsequent health effects due to environmental chemical exposures. [Copyright &y& Elsevier]

Radiation-induced tumors cannot be distinguished from tumors in general by means other than a statistical excess. Epidemiological studies are the only means by which answers can be given as regards the carcinogenic effect of ionizing radiation. Age at exposure is perhaps the most important host factor influencing cancer risk and it is generally believed that cancer risk decreases with increasing age at exposure. For most cancers the temporal pattern follows the natural incidence, i.e. the cancers do not occur before ages normally associated with increased incidence. The induction period for solid tumors is at least 10 years while the corresponding figure for leukemia is 2 years. The breast, thyroid, lung and bone marrow seem to be the most radiosensitive tissues, while the risk of chronic lymphatic leukemia and possibly Hodgkin's disease and prostatic cancer does not seem to increase after exposure to ionizing radiation. [ABSTRACT FROM AUTHOR]