Solid Cancer Incidence Research Articles

Assessing the Relative Biological Effectiveness of Neutrons across Organs of Varying Depth among the Atomic Bomb Survivors.

When assessing radiation-related risk among the atomic bomb survivors, choices in modeling approach can have an important impact on the results, which are then used to inform radiation protection standards throughout the world. The atomic bombings of Hiroshima and Nagasaki produced a mixed-field radiation exposure from two sources: neutrons and gamma rays. Neutrons are more densely ionizing and cause greater biological damage per unit absorbed dose, resulting in greater relative biological effectiveness (RBE) than gamma rays. To account for this, a combined weighted dose is typically calculated as the sum of the gamma-ray dose and 10 times the neutron dose in the Radiation Effects Research Foundation's reports of mortality, solid cancer incidence and other outcomes. In addition, the colon, which is often chosen as the whole-body representative organ in these analyses, is relatively deep in the body and therefore its dose calculation involves heavy body shielding of neutrons and a low neutron/gamma-ray ratio. With added follow-up and recently updated doses, we used a data-driven approach to determine the best-fitting neutron RBE for a range of organs of varying depth. Aggregated person-year tables of solid cancer incidence (1958-2009) from the Life Span Study were created with separate neutron and gamma-ray DS02R1 doses for several organs including breast, brain, thyroid, bone marrow, lung, liver and colon. Typical excess relative risk models estimating the linear effect of radiation dose were fitted using a range of neutron weights (1-250) to calculate combined dose for each organ, and model deviances were compared to assess fit. Furthermore, models using separate terms for gamma-ray and neutron dose were also examined, wherein the ratio of the neutron/gamma-ray linear terms indicated the best estimate of the RBE. The best-fitting RBE value for the traditional weighted colon dose was 80 [95% confidence interval (CI): 20-190], while the RBEs for other organs using weighted doses ranged from 25 to 60, with the best-fitting weights and confidence interval widths both incrementally increasing with greater depth of organ. Models using separate neutron- and gamma-ray-dose terms gave similar results to weighted linear combinations, with a neutron/gamma-ray term ratio of 79.9 (95% CI: 18.8-192.3) for colon. These results indicated that the traditionally modeled RBE of 10 may underestimate the effect of neutrons across the full dose range, although these updated estimates still have fairly wide confidence bounds. Furthermore, the colon is among the deepest of organs and may not be the best choice as a single surrogate organ dose, as it may minimize the role of the neutrons. Future work with more refined organ doses could shed more light on RBE-related information available in the Life Span Study data.

Incidence of solid cancer in patients with follicular lymphoma

Introduction: Patients with follicular lymphoma (FL) have classically had a higher risk of solid cancers than the general population, but there is little data available in patients diagnosed and treated with modern day regimens.Material and methods: We conducted a retrospective multicenter study assessing the cumulative incidence of solid cancers other than nonmelanoma skin cancer in patients with FL between 1997 and 2016 and determined the standardized incidence ratio (SIR) to compare the incidence of solid cancers with that of the general populationResults: Among 1002 FL patients with 7 years of median follow-up, we found 74 solid cancers (most common breast [n = 19], lung and colon [n = 9 each]). The cumulative incidence was 3.8% at 5 years (95%CI 2.6–5.2) from the time of diagnosis and 4.4% at 5 years (95%CI 3.1–5.9%) from the time of front-line treatment. Although a comparison of all front-line strategies did not reveal differences in the risk of solid cancers, patients treated with anthracycline-based regimens appeared to have a lower incidence than those treated with bendamustine-based strategies (2.8% vs. 6.9%). However, patients receiving the former regimen were younger than the latter. On multivariable analysis, older age was correlated with the incidence of solid cancer and bendamustine-based treatment was of borderline significance. SIR for any solid cancer was 1.22 (95%CI 0.91–1.64), indicating no increased risk of solid cancer in patients with FL over that of the general population. However, on subgroup analyses, female patients treated with bendamustine-based strategies appeared to have a greater risk (SIR 3.85 [95%CI 1.45–10.27])Discussion: The incidence of solid cancer in this cohort of patients with FL was low and not greater than in the general population. However, the risk may be greater in female patients treated with bendamustine.

Radiation-Related Risk of Cancers of the Upper Digestive Tract among Japanese Atomic Bomb Survivors.

As a follow-up to the comprehensive work on solid cancer incidence in the Life Span Study (LSS) cohort of atomic bomb survivors between 1958 and 1998, we report here on updated radiation risk estimates for upper digestive tract cancers. In this study, we added 11 years of follow-up (1958-2009), used improved radiation dose estimates, considered effects of smoking and alcohol consumption and performed dose-response analyses by anatomical sub-site. In examining 52 years'worth of data, we ascertained the occurrence of 394 oral cavity/pharyngeal cancers, 486 esophageal cancers and 5,661 stomach cancers among 105,444 subjects. The radiation risk for oral cavity/pharyngeal cancer, other than salivary gland, was elevated but not significantly so. In contrast, salivary gland cancer exhibited a strong linear dose response with excess relative risk (ERR) of 2.54 per Gy [95% confidence interval (CI): 0.69 to 6.1]. Radiation risk decreased considerably with increasing age at time of exposure (-66% per decade, 95% CI: -88% to -32%). The dose response for esophageal cancer was statistically significant under a simple linear, linear-quadratic and quadratic model. Both linear-quadratic and quadratic models described the data better than a simple linear model and, of the two, the quadratic model showed a marginally better fit based on the Akaike Information Criteria. Sex difference in linear ERRs was not statistically significant; however, when the dose-response shape was allowed to vary by sex, statistically significant curvature was found among males, with no evidence of quadratic departure from linearity among females. The risk for stomach cancer increased significantly with dose and there was little evidence for quadratic departure from linearity among either males or females. The sex-averaged ERR at age 70 was 0.33 per Gy (95% CI: 0.20 to 0.47). The ERR decreased significantly (-1.93 power of attained age, 95% CI: -2.94 to -0.82) with increasing attained age, but not with age at exposure, and was higher in females than males (P = 0.02). Our results are largely consistent with the results of prior LSS analyses. Salivary gland, esophageal and stomach cancers continue to show significant increases in risk with radiation dose. Adjustment for lifestyle factors had almost no impact on the radiation effect estimates. Further follow-up of the LSS cohort is important to clarify the nature of radiation effects for upper digestive tract cancers, especially for oral cavity/pharyngeal and esophageal cancers, for which detailed investigation for dose-response shape could not be conducted due to the small number of cases.

Effect of Heterogeneity in Background Incidence on Inference about the Solid-Cancer Radiation Dose Response in Atomic Bomb Survivors.

A recent analysis of solid cancer incidence in the Life Span Study of atomic bomb survivors (Hiroshima and Nagasaki, Japan) found evidence of a nonlinear, upwardly curving radiation dose response among males but not among females. Further analysis of this new and unexpected finding was necessary. We used two approaches to investigate this finding. In one approach, we excluded individual cancer sites or groups of sites from all solid cancers. In the other approach, we used joint analysis to allow for heterogeneity in background-rate parameters across groups of cancers with dissimilar trends in background rates. Exclusion of a few sites led to the disappearance of curvature among males in the remaining collection of solid cancers; some of these influential sites have unique features in their background age-specific incidence that are not captured by a background-rate model fit to all solid cancers combined. Exclusion of a few sites also led to an appearance of curvature among females. Misspecification of background rates can cause bias in inference about the shape of the dose response, so heterogeneity of background rates might explain at least part of the all solid cancer dose-response difference in curvature between males and females. We conclude that analysis based on all solid cancers as a single outcome is not the optimal method to assess radiation risk for solid cancer in the Life Span Study; joint analysis with suitable choices of cancer groups might be preferable by allowing for background-rate heterogeneity across sites while providing greater power to assess radiation risk than analyses of individual sites.

Распределение индивидуальных доз в когорте людей в результате радиоактивного загрязнения реки Течи

Purpose: Descriptive analysis of the distributions of organ/tissue doses for individuals exposed to radiation as a result of liquid waste releases into the Techa River by the Mayak Production Association (PA) in 1949–1956. 
 Material and methods: The dosimetry system TRDS-2016D has been used to compute individual doses of external and internal exposures. TRDS-2016D databases include information on radionuclide intakes and dose rates in air for settlements located in the contaminated areas of the Techa River and the East Ural Radioactive Trace (EURT). Combining these village-average data with the residence history and age of a particular person, the system produces an individual scenario of external exposure and individual radionuclide intakes and then calculates corresponding external and internal doses from the Techa River and EURT. Available 90Sr-body-burden measurements and available information on individual household locations relative to the contaminated river have been used for refinement of individual dose estimates. 
 Results: Individual doses have been calculated for 29,647 persons included in the Techa River Cohort (TRC). According to residence history data, 5,280 members of the TRC were additionally exposed due to residency in the EURT villages. The cohort-average dose for the majority of extra-skeletal tissues does not exceed 100 mGy, while for the red bone marrow (RBM) it is equal to 350 mGy. In addition to the doses from the Techa River and EURT, individual thyroid doses for TRC members exposed to the Mayak PA atmospheric 131I releases have been calculated in a separate computer program. The cohort–average thyroid dose is 210 mGy. Maximum doses (about 1 Gy to the majority of extra-skeletal tissues and over 7 Gy to the thyroid and RBM) are observed for the persons who lived in their childhood and adolescence in the upper Techa region at close distance to the Mayak PA.
 Conclusion: The TRC members were exposed to chronic radiation over a wide range of doses, but at low-to-moderate-dose rates. Estimates of absorbed doses can be used to analyze the dose dependences of the incidence of solid cancers and leukemias. This can make it possible to verify risk coefficients of low-dose-rate effects of ionizing radiation which can be used for radiation protection purposes.

Renal cell carcinoma in kidney transplant recipients at Guy’s and King’s College Hospital (UK) between 1987-2018.

e16066 Background: The increased incidence of cancer after renal transplantation is well recognised. Differences in cancer risk depend on the type of cancer but overall the incidence of solid cancer in kidney transplant recipient is at least twofold. Long term immunosuppression, oncogenic viruses and changes in immune surveillance are contributing factors. The incidence of renal cell carcinoma (RCC) is approximately six-fold greater than in the general population. Screening for RCC in the post-transplantation setting is not routine. Methods: Retrospective case series of kidney transplant recipients who underwent transplantation between 1987 and 2018 at Guy’s Hospital (London, UK). Collected data on patients who developed RCC post-transplant included: baseline demographics, renal disease, transplant survival, tumour characteristics, cancer treatment and survival. Results: 2968 patients underwent kidney transplantation between 1987 and 2018 at our Centre. 52 patients (1.8%) developed RCC. 40 (74%) were male with a median age of 51 years. 37% (71%) were white and 12 (23%) were black. The causes of end stage kidney disease included IgA nephropathy, hypertension and polycystic kidney disease. Median time to RCC diagnosis after transplant was 9 years (range 0-27). 86% of patients presented with stage 1/2 tumours, with the majority (72%) occurring in native kidneys. Most underwent radical nephrectomy although 5 patients were managed with radiofrequency-ablation (RFA) or surveillance (donor kidneys). Of 6 patients with metastatic disease, 5 received pazopanib and 1 everolimus. 4 patients continued systemic therapy for over 3 months and all derived clinical benefit with a median drug exposure of 19 months .15 patients required further kidney transplant or dialysis. Overall only 2 patients died from RCC. Conclusions: This retrospective study is the largest single-centre UK study to our knowledge. Kidney transplant recipients experience a marked increased risk of developing RCC. Most diagnosed RCCs are small and disease-specific mortality is low. With a third of tumours arising in donor organs, questions around optimum loco-regional approach and screening of high-risk population remain unanswered.

Gold quantum dots impair the tumorigenic potential of glioma stem-like cells via β-catenin downregulation in vitro.

BackgroundOver the past several decades, the incidence of solid cancers has rapidly increased worldwide. Successful removal of tumor-initiating cells within tumors is essential in the field of cancer therapeutics to improve patient disease-free survival rates. The biocompatible multivarient-sized gold nanoparticles (MVS-GNPs) from quantum dots (QDs, <10 nm) to nanosized (up to 50 nm) particles have vast applications in various biomedical areas including cancer treatment. The role of MVS-GNPs for inhibition of tumorigenic potential and stemness of glioma was investigated in this study.MethodsHerein, MVS-GNPs synthesized and characterized by means of X-ray diffraction pattern (XRD) and transmission electron microscopy (TEM) techniques. Afterwards, interaction of these GNPs with glioma stem-cell like cells along with cancer cells were evaluated by MTT, cell motility, self-renewal assays and biostatistics was also applied.ResultsAmong these GNPs, G-QDs contributed to reduce metastatic events and spheroid cell growth, potentially blocking the self-renewal ability of these cells. This study also uncovers the previously unknown role of the inhibition of CTNNB1 signaling as a novel candidate to decrease the tumorigenesis of glioma spheroids and subsequent spheroid growth. The accurate and precise biostatistics results were obtained at quantify level.ConclusionIn summary, G-QDs may exhibit possible contribution on suppressing the growth of tumor-initiating cells. These data reveal a unique therapeutic approach for the elimination of residual resistant stem-like cells during cancer treatment.

Радиационные риски российских участников ликвидации последствий аварии на Чернобыльской АЭС за период 1992-2017 гг. Часть I: заболеваемость солидными раками

Радиационные риски российских участников ликвидации последствий аварии на Чернобыльской АЭС за период 1992-2017 гг. Часть I: заболеваемость солидными раками

The Linear No-Threshold Model of Low-Dose Radiogenic Cancer: A Failed Fiction.

The linear no-threshold (LNT) model for low-dose, radiogenic cancer has been a fixture of radiation protection and regulatory requirements for decades, but its validity has long been contested. This article finds, yet again, more questionable data and analyses purporting to support the model, this within the “gold-standard” data set for estimating radiation effects in humans. Herein is addressed a number of significant uncertainties in the Radiation Effects Research Foundation’s Life Span Study (LSS) cohort of atomic bomb survivors, especially in its latest update of 2017, showing that the study’s support of the LNT model is not evidence based. We find that its latest 2 analyses of solid cancer incidence ignore biology and do not support the LNT model. Additionally, we identify data inconsistencies and missing causalities in the LSS data and analyses that place reliance on uncertain, imputed data and apparently flawed modeling, further invalidating the LNT model. These observations lead to a most credible conclusion, one supporting a threshold model for the dose–response relationship between low-dose radiation exposure and radiogenic cancer in humans. Based upon these findings and those cited from others, it becomes apparent that the LNT model cannot be scientifically valid.

Evaluation of Second Solid Cancers After Hematopoietic Stem Cell Transplantation in European Patients

Incidence and risk factors of second solid cancers (SSCs) that occur after hematopoietic stem cell transplantation (HSCT) are well documented. However, clinical outcome data of patients who developed an SSC after HSCT are limited. To assess the outcome of patients with an SSC occurring after HSCT from the time of SSC diagnosis. This cohort study used data of 4065 patients from 26 countries registered with the European Society for Blood and Marrow Transplantation, which has maintained clinical data since 1977 of patients who received a transplant. Information from all patients who underwent a transplant in Europe and had an SSC diagnosis between January 1, 2000, and December 31, 2014, was extracted. The cohort included patients with 18 different cancers. Data analysis was conducted from September 3, 2017, to March 17, 2018. Median and 5-year age-standardized overall survival, causes of death, risk factor multivariate analysis using a clustered Cox proportional hazard regression model, and standardized mortality ratio were calculated for each of the 18 types of SSC. In total, 220 617 patients underwent a transplant, of whom only 4065 (1.8%) patients with a second solid cancer after HSCT were included in the study. Among the 4065 patients, 2321 (57.1%) were men and 1744 (42.9%) were women, with a mean (range) age of 59.1 (3.2-82.3) years at diagnosis of second solid cancer. The 5-year age-standardized overall survival was 47% (95% CI, 45%-49%). The 5-year overall survival rate after SSC diagnosis was poor for pancreas, lung, hepatobiliary, esophageal, brain, and gastric cancers, with a median survival between 0.6 and 1 year. The 5-year overall survival was intermediate for endometrial, colorectal, sarcomas, ovarian, bladder, oropharyngeal, and kidney cancers, with a median survival between 2 and 10 years. The 5-year overall survival was more favorable for melanoma, breast, prostate, cervix, and thyroid cancers, with a median survival of 10 or more years. Additional transplant-associated factors for mortality for patients treated with allogeneic HSCT were age at transplant, donor type, conditioning regimen, and graft-vs-host disease. In total, 1777 patients (43.7%) died, of which 1256 (74.8%) were from SSC, 344 (20.5%) from primary disease, and 79 (4.7%) from other causes. Standardized mortality ratio was higher, compared with de novo solid cancers, for melanoma, prostate, breast, kidney, bladder, colorectal, and endometrial cancers but not for the other cancers. The outcome of SSC is mainly dependent on the type of second cancer; thus, future studies should investigate the reasons the standardized mortality ratio is higher for some cancers to identify whether patients with these cancers should be treated differently and to help in screening and counseling patients who developed an SSC after HSCT.

Probability Distribution of Dose and Dose-Rate Effectiveness Factor for use in Estimating Risks of Solid Cancers From Exposure to Low-Let Radiation.

This paper presents an analysis to develop a subjective state-of-knowledge probability distribution of a dose and dose-rate effectiveness factor for use in estimating risks of solid cancers from exposure to low linear energy transfer radiation (photons or electrons) whenever linear dose responses from acute and chronic exposure are assumed. A dose and dose-rate effectiveness factor represents an assumption that the risk of a solid cancer per Gy at low acute doses or low dose rates of low linear energy transfer radiation, RL, differs from the risk per Gy at higher acute doses, RH; RL is estimated as RH divided by a dose and dose-rate effectiveness factor, where RH is estimated from analyses of dose responses in Japanese atomic-bomb survivors. A probability distribution to represent uncertainty in a dose and dose-rate effectiveness factor for solid cancers was developed from analyses of epidemiologic data on risks of incidence or mortality from all solid cancers as a group or all cancers excluding leukemias, including (1) analyses of possible nonlinearities in dose responses in atomic-bomb survivors, which give estimates of a low-dose effectiveness factor, and (2) comparisons of risks in radiation workers or members of the public from chronic exposure to low linear energy transfer radiation at low dose rates with risks in atomic-bomb survivors, which give estimates of a dose-rate effectiveness factor. Probability distributions of uncertain low-dose effectiveness factors and dose-rate effectiveness factors for solid cancer incidence and mortality were combined using assumptions about the relative weight that should be assigned to each estimate to represent its relevance to estimation of a dose and dose-rate effectiveness factor. The probability distribution of a dose and dose-rate effectiveness factor for solid cancers developed in this study has a median (50th percentile) and 90% subjective confidence interval of 1.3 (0.47, 3.6). The harmonic mean is 1.1, which implies that the arithmetic mean of an uncertain estimate of the risk of a solid cancer per Gy at low acute doses or low dose rates of low linear energy transfer radiation is only about 10% less than the mean risk per Gy at higher acute doses. Data were also evaluated to define a low acute dose or low dose rate of low linear energy transfer radiation, i.e., a dose or dose rate below which a dose and dose-rate effectiveness factor should be applied in estimating risks of solid cancers.

Cancer risk incidence from hypothetical accident of VVER-1000 nuclear power plant based on BEIR VII model

AbstractBackgroundSafety is a mandatory issue during the operation of a nuclear power plant. A nuclear reactor can have some atmospheric dispersion due to any errors in the safety system.PurposeThe aim of this study is to estimate the cancer risk incidence for different body organs due to accidentally released radionuclides from Bushehr Nuclear Power Plant (BNPP).Materials and methodsThe assumed hypothesis was atmospheric dispersion of radionuclide into the environment due to the safety failure of BNPP. Total effective dose equivalent (TEDE) from radionuclide diffusion in the medium was calculated using HOTSPOT code at two different wind speeds. Finally, the risk of cancer incidence for different organs of male and female sex has been estimated by Biologic Effects of Ionizing Radiation (BEIR) VII model.ResultsThe results showed that with increasing the exposure age and attained age, the risk of cancer incidence for different organs is decreased. The value of TEDE was increased at lower wind speed. The most probable organ for cancer incidence at different levels of TEDE in male and female sex was colon and bladder, respectively. On the other hand, prostate and uterus had the lowest radiation sensitivity and cancer risk incidence in male and female sex, respectively. Increasing the wind speed reduces the risk of cancer incidence for all of organs understudy.ConclusionBased on the obtained results, it can be concluded that the younger persons are more subject to the cancer risk incidence because of both the intrinsically greater radio-sensitivity of their organs and their longer remaining life expectancy during which a cancer may develop. The overall risk of cancer incidence as well as the site specific solid cancer incidence were highly dependent to the sex of exposed person, so that the female sex was more exposed to the cancer risk incidence at all of the irradiation levels understudy.

Selection of reference groups in the Life Span Study of atomic bomb survivors.

In cohort studies, unbiased estimation of exposure-outcome associations requires selection of an appropriate reference group of unexposed individuals. We illustrate strategies for analyzing cohort data with multiple potential reference groups. We analyzed the association between radiation exposure and incidence of first primary solid cancer among 105,444 participants of the Life Span Study (Hiroshima and Nagasaki, Japan, 1958-2009). Potential reference groups included zero-dose survivors at different ground distances from the hypocenter (internal) and city residents who were not in either city at the time of the bombings (external). DS02R1 weighted absorbed colon doses were estimated by the DS02 dosimetry system. Piecewise constant hazard models estimated excess relative risks of first primary solid cancer. We focused on sex-averaged excess relative risks and the shape of the dose-response curve. A model with internal standardization provided a sex-averaged excess relative risk of 0.510, 95% confidence interval: (0.414, 0.612) per gray of weighted absorbed colon dose, as well as strong evidence of a curvilinear dose response among males (P=0.008). Selection of not-in-city residents as the reference group resulted in a larger excess relative risk of 0.560, 95% confidence interval: (0.467, 0.657) per gray, and reduced evidence of a curvilinear dose response among males (P=0.042). These differences were particularly apparent at weighted absorbed colon doses <1 gray. In cohort studies, selection of an appropriate reference group requires understanding of the nature of unmeasured confounding to which the results could be sensitive.

The LSS Cohort of Atomic Bomb Survivors and LNT. Comments on ''Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958-2009" (Radiat Res 2017; 187:513-37) and "Reply to the Comments by Mortazavi and Doss" (Radiat Res 2017; 188:369-71).

The LSS Cohort of Atomic Bomb Survivors and LNT. Comments on ''Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958-2009" (Radiat Res 2017; 187:513-37) and "Reply to the Comments by Mortazavi and Doss" (Radiat Res 2017; 188:369-71).

Reply to the Comments by Mortazavi and Doss on "Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958-2009" (Radiat Res 2017; 187:513-537).

Reply to the Comments by Mortazavi and Doss on "Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958-2009" (Radiat Res 2017; 187:513-537).

Comments on "Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958-2009" (Radiat Res 2017; 187:513-537)

Comments on "Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958-2009" (Radiat Res 2017; 187:513-537)

Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958-2009.

This is the third analysis of solid cancer incidence among the Life Span Study (LSS) cohort of atomic bomb survivors in Hiroshima and Nagasaki, adding eleven years of follow-up data since the previously reported analysis. For this analysis, several changes and improvements were implemented, including updated dose estimates (DS02R1) and adjustment for smoking. Here, we focus on all solid cancers in aggregate. The eligible cohort included 105,444 subjects who were alive and had no known history of cancer at the start of follow-up. A total of 80,205 subjects had individual dose estimates and 25,239 were not in either city at the time of the bombings. The follow-up period was 1958-2009, providing 3,079,484 person-years of follow-up. Cases were identified by linkage with population-based Hiroshima and Nagasaki Cancer Registries. Poisson regression methods were used to elucidate the nature of the radiation-associated risks per Gy of weighted absorbed colon dose using both excess relative risk (ERR) and excess absolute risk (EAR) models adjusted for smoking. Risk estimates were reported for a person exposed at age 30 years with attained age of 70 years. In this study, 22,538 incident first primary solid cancer cases were identified, of which 992 were associated with radiation exposure. There were 5,918 cases (26%) that occurred in the 11 years (1999-2009) since the previously reported study. For females, the dose response was consistent with linearity with an estimated ERR of 0.64 per Gy (95% CI: 0.52 to 0.77). For males, significant upward curvature over the full dose range as well as restricted dose ranges was observed and therefore, a linear-quadratic model was used, which resulted in an ERR of 0.20 (95% CI: 0.12 to 0.28) at 1 Gy and an ERR of 0.010 (95% CI: -0.0003 to 0.021) at 0.1 Gy. The shape of the ERR dose response was significantly different among males and females (P = 0.02). While there was a significant decrease in the ERR with increasing attained age, this decrease was more rapid in males compared to females. The lowest dose range that showed a statistically significant dose response using the sex-averaged, linear ERR model was 0-100 mGy (P = 0.038). In conclusion, this analysis demonstrates that solid cancer risks remain elevated more than 60 years after exposure. Sex-averaged upward curvature was observed in the dose response independent of adjustment for smoking. Findings from the current analysis regarding the dose-response shape were not fully consistent with those previously reported, raising unresolved questions. At this time, uncertainties in the shape of the dose response preclude definitive conclusions to confidently guide radiation protection policies. Upcoming results from a series of analyses focusing on the radiation risks for specific organs or organ families, as well as continued follow-up are needed to fully understand the nature of radiation-related cancer risk and its public health significance. Data and analysis scripts are available for download at: http://www.rerf.or.jp .

Reduced risk of all-cancer and solid cancer in Taiwanese patients with rheumatoid arthritis treated with etanercept, a TNF-α inhibitor.

Biologics has been widely used in the treatment of rheumatoid arthritis. We aimed to determine whether etanercept, a TNF-α inhibitor (TNFi) that is used to treat patients with rheumatoid arthritis (RA), affects cancer risk.This retrospective matched cohort study used data in the Registry of Catastrophic Illness Database in Taiwan from January 1, 1996 to December 31, 2010. RA, all-cancer, and solid cancer were defined using International Classification of Disease codes (ICD-9-CM 714.X, 140-208, and 140-199, respectively). Cox proportional hazard modeling was used to estimate the hazard ratio (HR) of cancer in all TNFi-treated RA patients, with a focus on the risk in the etanercept-treated patients, after adjusting for comorbidities and concomitant medication.In this Taiwanese dataset, there were 1111 TNFi-treated RA patients and 16,812 RA patients who were naive to all biologics identified. Among the 1002 pairs of etanercept-treated and biologic-naive patients who were matched 1-to-1 for age, gender, RA duration, methotrexate-use, and index date of TNFi prescription, the mean age was 48.9 ± 15.0 years. The highest proportion of patients was in the age subgroup of 30 to 60 years (63.8%). Most patients (77.2%) were women. The mean RA duration before etanercept treatment was 2.0 ± 1.5 years. During a mean 2.1 years of observation, etanercept was associated with significant risk reduction for all-cancer (HR 0.59, 0.36-0.98) and solid cancer (HR 0.46, 0.27-0.79) relative to the matched biologic-naive patients.The current study explored the safety profile of TNFi and identified a potential benefit of etanercept on the incidence of all-cancer and solid cancer in RA patients.

ADDITION TO THE QUASI-BIOLOGICAL MODEL OF RADIOGENIC CANCER MORBIDITY

Object: The purpose was to refine the quasi-biological model of the incidence of radiogenic solid cancer (published by the authors earlier in the journal “Radiation hygiene”) to ensure better consistency with the Japanese cohort data and with the ICRP model in part of the description of the effect of age at exposure. Results: Initial presuppositions of a mathematical model was supplemented by the assumption that stem cells, received the “pre-cancerous” defect of DNA, with a higher probability compared to the intact cells follow the path of reproduction but not of differentiation. Structure of the refined model and its properties did not change, but one parameter was added. Analysis of the base mathematical relations of the supplemented model showed that there was no contradiction between the models of radiogenic cancer incidence presented in the Publication 103 ICRP and in the UNSCEAR 2006, despite their external differences. Conclusion: Further work with the model requires the verification of parameter values by comparison with the epidemiological data, primarily with data on the incidence of solid cancers in the Japanese cohort. However, since some of the assumptions of the model, including the new one, are not purely radiobiological, it would require analysis of a wider range of biological and cancer patterns.

Analysis of solid cancer incidence risk among the population exposed in the East Urals Radioactive Trace over 1957–2009

Objective: Assessment of solid cancer incidence risk in the Chelyabinsk subcohort of the East Urals Radioactive Trace over the 53-year period of follow-up with use of the individualized doses accumulated in the soft tissues calculated on the basis of the new dosimetric system TRDS-2016. Materials and methods: The thermal explosion of the storage tank of the «Mayak» production Association radioactive waste in September, 1957 led to the formation of the East Urals Radioactive Trace and radiation exposure of the population living on the territory of the trace. Members of the created cohort received chronic external and internal radiation exposure. The mean dose to the soft tissues over the entire follow-up period amounted to 30 mGy, maximum – 960 mGy. The number of the study cohort is 21 394 persons. Over 53 years (from 1957 to 2009) 1426 cases of solid cancer excluding 73 hemoblastoses and 101 cases of non-melanoma skin cancer are registered in the cohort on the catchment area. Person-years at risk amount to 437 719. Individualized doses for the cohort members were evaluated on the basis of the improved dosimetric system developed by the specialists of the Urals Research Center for Radiation Medicine. The analysis was carried out by means of the Poisson regression method with the use of the software AMFIT. Confidence intervals were calculated using the maximum likelihood estimation. Results: Risk analysis of solid cancer incidence in Chelyabinsk subcohort of the East Urals Radioactive Trace has been carried out for the first time. A significant increase in solid cancer incidence risk with increasing the dose was obtained for the cohort members who were followed-up for 53 years. The excess relative risk per dose is 0.049/100mGy (90% of DI: 0.003; 0.010) according to the linear model. No significant effect modification of the excess relative risk value due to non-radiation factors was revealed. The results of the study demonstrate that the value of excess relative risk of solid cancer incidence per unit dose after chronic exposure at low or moderate doses can be compared to that at high doses.