Метод оценки радиационных рисков заболеваемости солидными злокачественными новообразованиями, учитывающий возможные ошибки в постановке и регистрации диагнозов

Purpose: Estimated radiation risks used for radiation protection purposes have been based primarily on the Life Span Study (LSS) of atomic bomb survivors who received brief exposures at high dose rates, many with high doses. Information is needed regarding radiation risks from low dose-rate (LDR) exposures to low linear-energy-transfer (low-LET) radiation. We conducted a meta-analysis of LDR epidemiologic studies that provide dose-response estimates of total solid cancer risk in adulthood in comparison to corresponding LSS risks, in order to estimate a dose rate effectiveness factor (DREF).Materials and methods: We identified 22 LDR studies with dose-response risk estimates for solid cancer after minimizing information overlap. For each study, a parallel risk estimate was derived from the LSS risk model using matching values for sex, mean ages at first exposure and attained age, targeted cancer types, and accounting for type of dosimetric assessment. For each LDR study, a ratio of the excess relative risk per Gy (ERR Gy−1) to the matching LSS ERR risk estimate (LDR/LSS) was calculated, and a meta-analysis of the risk ratios was conducted. The reciprocal of the resultant risk ratio provided an estimate of the DREF.Results: The meta-analysis showed a LDR/LSS risk ratio of 0.36 (95% confidence interval [CI] 0.14, 0.57) for the 19 studies of solid cancer mortality and 0.33 (95% CI 0.13, 0.54) when three cohorts with only incidence data also were added, implying a DREF with values around 3, but statistically compatible with 2. However, the analyses were highly dominated by the Mayak worker study. When the Mayak study was excluded the LDR/LSS risk ratios increased: 1.12 (95% CI 0.40, 1.84) for mortality and 0.54 (95% CI 0.09, 0.99) for mortality + incidence, implying a lower DREF in the range of 1–2. Meta-analyses that included only cohorts in which the mean dose was <100 mGy yielded a risk ratio of 1.06 (95% CI 0.30, 1.83) for solid cancer mortality and 0.58 (95% CI 0.10, 1.06) for mortality + incidence data.Conclusions: The interpretation of a best estimate for a value of the DREF depends on the appropriateness of including the Mayak study. This study indicates a range of uncertainty in the value of DREF between 1 and about 2 after protracted radiation exposure. The LDR data provide direct evidence regarding risk from exposures at low dose rates as an important complement to the LSS risk estimates used for radiation protection purposes.

Radiological protection is based on the assumption that any additional exposure to ionizing radiation produces an increased risk of stochastic adverse health effects. The ICRP has adopted linear no-threshold (LNT) dose-response relationships to derive health risks associated with low doses of radiation and this implies that the risks of cancer and hereditary effects are directly proportional to the dose received, no matter how small the dose. The LNT assumption has been criticised over the years both by those who consider that it underestimates the risk and by those who believe that it is overly conservative. A few years ago, most of the pressure on ICRP came from those who believed that the risks per unit dose adopted at low doses were too small, but in recent years the pressure has been coming from the opposite direction. Strictly speaking, ICRP feels that the most likely form of the dose-response relationship for low LET radiation is linear-quadratic (i.e. sub-linear at low doses), and for cancer they approximate this by two linear relations, that for the low dose region having a slope (risk per unit dose) half of that for the high dose region, represented by a DDREF of 2. Nevertheless, there are those (particularly in the US and France) who argue that there is no direct evidence for stochastic effects being produced by low doses of radiation, and that the appropriate dose-response relationship has a threshold dose below which no risk to health exists, or even that low doses of radiation are beneficial (`radiation hormesis').

There is evidence pointing to a possible role of diet on cancer etiology. Prior studies evaluating the relationship between fish consumption and lung cancer risk reported inconclusive results. The aim of this study was to achieve a comprehensive assessment of the relationship between fish consumption and lung cancer risk through systematic review and meta-analysis. Case control and cohort studies up to September 1, 2012 about fish consumption and lung cancer risk were confirmed by an online search. Separate relative risk (RR) or odds ratio (OR) estimates with 95% confidence interval (CI) of the relationship between lung cancer risk and fish consumption level from the included articles were combined by Stata11.0 software. Publication bias was evaluated by Egger's linear regression test and funnel plot. Twenty articles (17 case-control and 3 cohort studies) comprising 8799 cases of lung cancer and 17,072 noncases were included in the final analysis. The pooled results from all studies indicated that high fish consumption was significantly associated with a decreased risk of lung cancer (pooled RR: 0.79; 95% CI: 0.69–0.92). There was heterogeneity among the studies (I2 = 73%, P < 0.05). Pooled RR in case control and cohort studies were 0.76 (95% CI: 0.63–0.91) and 0.95 (95% CI: 0.73–1.24), respectively. Omission of any single study had little effect on the combined risk estimates. This article had no publication bias. This study identifies a significant association between fish consumption and lung cancer, confirming a protective role of fish in lung cancer. More well-designed prospective studies are required to further verify the effect of fish consumption on lung cancer.

Sepsis is a severe systemic inflammatory immune response to infection, which may lead to multiple organ failure and is associated with a 70% death rate. The risk of sepsis is higher in immunosuppressed individuals such as cancer patients. The risk of sepsis-related death among cancer patients may differ by cancer site and the administered cancer treatment. We examined the differences in the risk of sepsis-related mortality by cancer site and cancer treatment type among the 103,898 Hawaii participants of the Multiethnic Cohort Study (MEC), including 29,255 prevalent and incident cancer cases, followed for the period of 17-22 years. The participants were men and women aged 45-75 at cohort entry, primarily of Japanese American, Native Hawaiian or White race/ethnicity. Incident cancer cases were identified through linkage with the Hawaii Tumor Registry. Deaths due to sepsis (n=1,818) were identified as those with a primary or contributing cause of death ICD-10= A40-A41. Relative risk ratios (RR) and 95% confidence intervals (CI) were estimated using competing risk Cox regression with age as the time metric and with adjustment for participants' sex, race/ethnicity, and comorbidities at baseline (diabetes, cardiovascular disease, hypertension and stroke). Stratified analyses were conducted by sex and racial/ethnic group. The risk of sepsis-related death was not significantly different between cohort participants with and without cancer diagnosis (RR: 0.95; 95% CI: 0.85-1.06). In cancer-specific analyses, colorectal cancer diagnosis was associated with higher risk of sepsis death (RR: 1.41; 95% CI: 1.12-1.80), while lung cancer diagnosis was associated with lower risk of sepsis death (RR: 0.41; 95% CI: 0.31-0.55) compared to patients with cancer at all other organ sites. These associations were consistent across sexes and racial/ethnic groups, but only the association with lung cancer was statistically significant within most sex/ethnic groups. No association was observed between chemotherapy and sepsis death. Radiation treatment was associated with lower risk of sepsis death (RR: 0.69; 95% CI: 0.57-0.83). This association was consistent across sexes and racial/ethnic groups but was only statistically significant among Japanese and White women, possibly reflecting larger size and number of cancer cases with radiation therapy in these groups. In this study, we found that the risk of sepsis-related mortality is differentially affected by cancer at certain sites and by the type of cancer treatment administered. Future research should focus on biological and molecular mechanisms underlying these associations, with the hope of reducing the incidence of sepsis and sepsis-associated mortality. Citation Format: Yurii B. Shvetsov, Mari Ogino, Chloe Asato, Lynne R. Wilkens, Loic LeMarchand, Michelle Matter. Association of cancer site and treatment type with the risk of sepsis-related mortality in a multiethnic Hawaii population [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5794.

ES26.01 The Impact of Specialist Nursing Intervention in Lung Cancer

Information about the consequences of human exposure to radiation in the former Soviet Union has recently become available. These data add new insights and provide possible answers to several important questions regarding radiation and its impact on occupational and public health. The 1986 Chernobyl accident initiated a major and early increase in childhood thyroid cancer that resulted from ingestion of iodine-131 (131I) by young children living in the most heavily contaminated areas of Belarus, Ukraine, and Russia. No significant additional cancer or other adverse medical effects have yet been reported in the affected populations and among clean-up workers. Major psychological stress independent of radiation dose has been observed in those people thought to be exposed. During the early days of the atomic energy program in the former Soviet Union, some unfortunate events occurred. The country's first atomic test in Semipalatinsk in 1949 exposed over 25,000 people downwind from the blast to significant doses of fission products, especially 131I. During the late 1940s and the early 1950s nuclear material production facilities were developed near Chelyabinsk in the South Ural Mountains, which resulted in major releases into the environment and significant overexposures for thousands of workers and nearby populations. Chronic radiation sickness was observed early in exposed workers, and increases in leukemia and other cancers were also reported. The series of plutonium inhalation-related lung cancers and fatalities among workers exposed in that first decade appears to be unique. Long-term consequences of chronic radiation sickness and four decades of follow-up are being described for the first time. Villagers downstream from the plant consumed high levels of 137Cs and 90Sr and, it is reported, manifested increases in leukemia from internal and external exposures. Although the 40-year databases for retrospective dosimetry epidemiology studies are just beginning to be integrated and evaluated, preliminary evaluations suggest that there may be graded, significant dose-rate amelioration factors for cancer and leukemia risks in workers and the general population relative to the risk data on the Japanese atomic bomb survivors. Even for plutonium-induced lung cancers in workers, such a dose-rate effect may be evident. These experiences give us insight into the consequences of protracted radiation at high and low doses and rates. If these findings are validated and confirmed, they can provide information that reduces some of the uncertainties in retrospective radiation dosimetry and radiation risk estimates (especially for low-level, chronic exposures) for activities related to medicine as well as the handling of nuclear materials and nuclear facility decommissioning, decontamination, and demilitarization.

Risk Factors for Incident Open-angle Glaucoma: The Barbados Eye Studies

Background The study of Japanese atomic bomb survivors, exposed briefly to radiation, finds the risk of radiation-induced lung cancer to be nearly three times greater for women than for men. Because protection standards for astronauts are based on individual lifetime risk projections, this sex-specific difference limits the time women can spend in space. Populations exposed to chronic or fractionated radiation were evaluated to learn whether similar differences exist when exposures occur gradually over years. Methods and materials Five occupational cohorts within the Million Person Study of Low-Dose Health Effects (MPS) and a Canadian Fluoroscopy Cohort Study (CFCS) of tuberculosis patients who underwent frequent chest fluoroscopic examinations are evaluated. Included are male and female workers at the Mound nuclear facility, nuclear power plants (NPP), and industrial radiographers (IR). Workers at the Mallinckrodt Chemical Works and military participants at aboveground nuclear weapons tests provide information on the risk among males. Cox proportional hazards and Poisson regression models were used to estimate sex-specific radiation risks for lung cancer and to compare any differences. Results Overall, 15,065 lung cancers occurred among the 443,684 subjects studied: 50,111 women and 395,573 men. The mean cumulative dose to the lung was 166.3 mGy (range 6 to 1,055 mGy) with the highest among the TB-fluoroscopy patients (mean 1,055 mGy). Mean lung dose for women in the worker cohorts was generally 4 times lower than for men. Of the 12 estimates of radiation-related risk, only one, for male IRs, showed a significant elevation (ERR 0.09; 95% CI 0.02–0.16, at 100 mGy). In contrast, the dose response for male NPP workers was negative (ERR −0.05; 95% CI −0.10, 0.01, at 100 mGy). Combined, these two cohorts provided little evidence for a radiation effect among males (ERR 0.01; 95% CI −0.04, 0.06, at 100 mGy). There was no significant dose-response among females within any cohort. There was no difference in the sex-specific estimates of lung cancer risk. Conclusions There was little evidence that chronic or fractionated exposures increased the risk of lung cancer. There were no differences in the risks of lung cancer between men and women. However, the sex-specific analyses are limited because of small numbers of women and relatively low doses. A more definitive study is ongoing of medical radiation workers which include 85,000 women and 85,000 men (overall mean dose 82 mGy, max 1,140 mGy). Additional understanding will come from the ongoing follow-up of the CFCS.

A causal relationship between protracted exposure to low-dose rate radiation and health effects remains unclear despite extensive international studies of nuclear workers. One potential reason is that radiation epidemiological studies that adjust for tobacco smoking, which heavily influences mortality, have been limited. In the present study, we examined radiation-related cancer risk by directly assessing the possible confounding effect of smoking, using data from two questionnaire surveys performed among Japanese nuclear workers in 1997 and 2003. Mortality follow-up was carried out for 71 733 male respondents for an average of 8.2 years during the observation period of 1999–2010. The mean cumulative dose was 25.5 mSv at the end of the follow-up period. Estimates of excess relative risk per Sv (ERRs/Sv) were obtained by Poisson regression. By adjusting for smoking directly on the basis of a linear dose-response model, we quantified the confounding effects of smoking on radiation risks. Statistically significant ERRs/Sv were found for all causes, all diseases, all non-cancer diseases, and liver cancer: 0.97 (90% confidence interval: 0.23, 1.78), 1.32 (0.40, 2.34), 1.87 (0.47, 3.49), and 4.78 (0.09, 11.68), respectively, without adjustment for smoking. However, the ERRs/Sv were no longer statistically significant after adjustment for smoking: 0.45 (−0.22, 1.19), 0.77 (−0.08, 1.72), 1.28 (−0.03, 2.79), and 3.89 (−0.46, 10.34), respectively. The ERRs/Sv for all cancers excluding leukaemia and lung cancer were not significant before adjustment for smoking, but declined after adjustment for smoking. The present study demonstrates that in this cohort of workers, smoking heavily distorts radiation risk estimates of mortality. The possibility of confounding by smoking depends on how strongly smoking is correlated with radiation exposure. If a correlation between smoking and radiation dose is suggested, smoking is an important confounder when assessing the radiation and health risks.

PurposeIn occupational epidemiology, the healthy worker survivor effect can manifest as a time-dependent confounder because healthier workers can accrue greater amounts of exposure over longer periods of employment. For example, in occupational studies of radiation exposure that focus on cumulative annualized radiation dose, workers can accrue greater amounts of cumulative radiation exposure over longer periods of employment, while workers with longer periods of employment can transition into jobs with a reduced potential for annualized radiation exposure. The extent to which confounding arising from the healthy worker survivor effect impacts radiation risk estimates is unknown. MethodsWe assessed the impact of the healthy worker survivor effect on estimates of radiation risk among nuclear workers in a Million Person Study cohort. In simulation studies, we contrasted the ability of marginal structural Cox models with inverse probability weighting and Cox proportional hazards models to account for time-dependent confounding arising from the healthy worker survivor effect. ResultsMarginal structural Cox models and Cox proportional hazards models with flexible functional forms for duration of employment provided reliable results. ConclusionsIt is crucial to flexibly adjust for duration of employment to account for confounding arising from the healthy worker survivor effect in occupational epidemiology.

Despite the importance of diversity of cancer trial participants with regard to race, ethnicity, age, and sex, there is little recent information about the representation of these groups in clinical trials. To characterize the representation of racial and ethnic minorities, the elderly, and women in cancer trials sponsored by the National Cancer Institute. Cross-sectional population-based analysis of all participants in therapeutic nonsurgical National Cancer Institute Clinical Trial Cooperative Group breast, colorectal, lung, and prostate cancer clinical trials in 2000 through 2002. In a separate analysis, the ethnic distribution of patients enrolled in 2000 through 2002 was compared with those enrolled in 1996 through 1998, using logistic regression models to estimate the relative risk ratio of enrollment for racial and ethnic minorities to that of white patients during these time periods. Enrollment fraction, defined as the number of trial enrollees divided by the estimated US cancer cases in each race and age subgroup. Cancer research participation varied significantly across racial/ethnic and age groups. Compared with a 1.8% enrollment fraction among white patients, lower enrollment fractions were noted in Hispanic (1.3%; odds ratio [OR] vs whites, 0.72; 95% confidence interval [CI], 0.68-0.77; P<.001) and black (1.3%; OR, 0.71; 95% CI, 0.68-0.74; P<.001) patients. There was a strong relationship between age and enrollment fraction, with trial participants 30 to 64 years of age representing 3.0% of incident cancer patients in that age group, in comparison to 1.3% of 65- to 74-year-old patients and 0.5% of patients 75 years of age and older. This inverse relationship between age and trial enrollment fraction was consistent across racial and ethnic groups. Although the total number of trial participants increased during our study period, the representation of racial and ethnic minorities decreased. In comparison to whites, after adjusting for age, cancer type, and sex, patients enrolled in 2000 through 2002 were 24% less likely to be black (adjusted relative risk ratio, 0.76; 95% CI, 0.65-0.89; P<.001). Men were more likely than women to enroll in colorectal cancer trials (enrollment fractions: 2.1% vs 1.6%, respectively; OR, 1.30; 95% CI, 1.24-1.35; P<.001) and lung cancer trials (enrollment fractions: 0.9% vs 0.7%, respectively; OR, 1.23; 95% CI, 1.16-1.31; P<.001). Enrollment in cancer trials is low for all patient groups. Racial and ethnic minorities, women, and the elderly were less likely to enroll in cooperative group cancer trials than were whites, men, and younger patients, respectively. The proportion of trial participants who are black has declined in recent years.

Objective: Ionizing radiation is widely used in the hospital for diagnostic and therapeutic procedures to patients and its usage increasing day by day. The aim of the study is to monitor the real-time radiation around the Shaheed Suhrawardy Medical College (ShSMC) hospital campus and estimation of radiation risk on public.&#x0D; Method: The real-time radiation monitoring around the ShSMC hospital was performed using digital portable radiation monitoring device (DPRMD). The DPRMD meets all European CE standards and the American “FCC 15 standard”. The DPRMD was placed at 1 meter above the ground on tripod and data collection time for each monitoring point (MP) was 1 hour. Each MP was marked out using Garmin eTrex GPS device. 32 MPs were chosen for collection of the real-time radiation dose rates around the ShSMC hospital campus in October 2020.&#x0D; Results: The real-time radiation dose rates around the ShSMC hospital campus were ranged from 0.37-3.39 µSv/hr with an average of 1.537 ± 0.359 µSv/hr. The annual effective dose on public were ranged from 1.326 ± 0.551 mSv to 4.902 ± 0.705 mSv with an average of 2.694 ± 0.629 mSv. The excess life-time cancer risk (ELCR) on public health was estimated based on the annual effective dose that ranged from 5.277×10ˆ-3 to 19.503×10ˆ-3 with an average value of 10.72×10ˆ-3 around the ShSMC hospital campus.&#x0D; Conclusion: Real-time radiation monitoring facilitates to ensure the safety of the radiation workers and the public from undue radiation hazard. The study also gives instant information of improper operation of radiation generating equipments and improper handling of radioactive substances in the hospital.

Rationale: A 4-protein biomarker panel (4MP) can improve estimation of lung cancer risk and identify individuals who may benefit most from lung cancer screening. In the current study, we evaluate the performance of the 4MP for risk determination of lung cancer in individuals undergoing lung cancer screening. Methods: We obtained two cohorts of samples from the National Lung Screening Trial (NLST). The first cohort consisted of 675 samples from individuals with CT scans without suspicious findings, including 135 eventually diagnosed with lung cancer and 540 matched control samples. The second cohort consisted of 715 samples from individuals with screen-detected pulmonary nodules, including 143 diagnosed with cancer and 572 matched controls. We additionally obtained plasma from 27 cases lung cancer cases and 1308 non-cases with screen-detected pulmonary nodules that were drawn from the University of British Columbia site of the International Lung Screening Trial (ILST). The 4MP was measured using a multiplex bead-based immunoassay using coefficients fixed from a previously developed logistic regression model. Performance was evaluated using receiver operating characteristic analysis, including computing the area under the curve (AUCs) as well as a net reclassification index (NRI) to estimate how well the 4MP improved existing risk prediction models such as the Brock nodule risk model. Results: In the NLST cohort with negative CTs, for those individuals eventually diagnosed with stage II or higher lung cancer, the 4MP showed an AUC of 0.67 (95% CI 0.59-0.74). For all those with advanced (stage III and higher), AUC was 0.71 (95% CI 0.61-0.81). For individuals diagnosed within 1 year of blood draw, the AUC was 0.71 (95% CI 0.51-0.91). In those with indeterminate nodules, the 4MP showed similar performance in both the NLST and ILST samples, with an AUC of 0.64 (95% CI 0.59-0.70) in those eventually diagnosed with stage II or higher lung cancer from the NLST. We further evaluated the performance of the 4MP to reclassify pulmonary nodules, roughly based on Lung-RADS risk category. This model was developed in the ILST samples and validated in the NLST samples. The 4MP, added to the Brock model, showed an NRI of 0.26 compared to the Brock model alone in the validation set. Conclusions: The 4MP may be a useful adjunct to screening, especially in identifying those who will develop more advanced stage disease in the following year. This could help to identify individuals who may benefit from closer clinical follow-up.

PurposeLong-term health risks of occupational exposures to uranium processing were examined to better understand potential differences with uranium underground miners and nuclear reactor workers.MethodsA cohort study of mortality of workers from Port Hope, Canada (1950–1999) and Wismut, Germany (1946–2008) employed in uranium milling, refining, and processing was conducted. Poisson regression was used to evaluate the association between cumulative exposures to radon decay products (RDP) and gamma-rays and causes of death potentially related to uranium processing.ResultsThe pooled cohort included 7431 workers (270,201 person-years of follow-up). Mean RDP exposures were lower than in miners while gamma-ray doses were higher than in reactor workers. Both exposures were highly correlated (weighted rho = 0.81). Radiation risks of lung cancer and cardiovascular diseases (CVD) in males were increased but not statistically significant and compatible with risks estimated for miners and reactor workers, respectively. Higher RDP-associated CVD risks were observed for exposures 5–14 years prior to diagnosis compared to later exposures and among those employed <5 years. Radiation risks of solid cancers excluding lung cancer were increased, but not statistically significant, both for males and females, while all other causes of death were not associated with exposures.ConclusionsIn the largest study of uranium processing workers to systematically examine radiation risks of multiple outcomes from RDP exposures and gamma-rays, estimated radiation risks were compatible with risks reported for uranium miners and nuclear reactor workers. Continued follow-up and pooling with other cohorts of uranium processing workers are necessary for future comparisons with other workers of the nuclear fuel cycle.

ABSTRACTObjective: To examine the association of maternal low birthweight (LBW) with infant LBW and infant LBW subgroups (i.e. moderate and very LBW), overall and among non-Hispanic (NH) white and NH black mothers.Design: We conducted a population-based cohort study in Allegheny County, Pennsylvania, using linked birth record data of NH white and NH black mother-infant pairs (N = 6,633) born in 1979–1998 and 2009–2011, respectively. The exposure of interest was maternal LBW (birthweight <2500 grams) while the outcomes were infant LBW and LBW subgroups – moderate LBW (1,500–2,499 grams) or very LBW (<1,500 grams). Logistic regression (binomial and multinomial) models were used to estimate adjusted Odds Ratios (ORs), Relative Risk Ratios (RRRs), and related 95% confidence intervals (CI). Stratified analyses were conducted to assess effect modification by mothers’ race.Results: Maternal LBW was associated with 1.53 (95%CI: 1.15–2.02) and 1.75 (95%CI: 1.29–2.37) –fold increases in risk of infant LBW and MLBW, respectively, but not VLBW (RRR = 0.86; 95%CI: 0.44–1.70). In race-stratified models, maternal LBW-infant LBW associations were observed among NH blacks (OR = 1.88; 95%CI: 1.32–2.66) and not among NH whites (OR = 1.03; 95%CI: 0.62–1.73) (P for interaction = 0.07). Among NH blacks, maternal LBW was associated with a 2.18 (95%CI: 1.49, 3.20) –fold increase in risk of infant MLBW, but not VLBW (RRR = 1.12; 95%CI: 0.54, 2.35). Among NH whites, LBW subgroup analyses could not be performed due to small numbers of VLBW infants among LBW mothers.Conclusion: Mothers who were LBW at their own birth were more likely to have MLBW infants. Maternal race modified associations of maternal LBW with infant LBW, particularly infant MLBW. Further research is needed in this area to understand the potential mechanisms involved in the transgenerational transmission of LBW risk and race-specific differences in the transmission.