Zhanat Carr

Cancer consequences of the Chernobyl accident: 20 years on

26 April 2006 marks the 20th anniversary of the Chernobyl accident. On this occasion, the World Health Organization (WHO), within the UN Chernobyl Forum initiative, convened an Expert Group to evaluate the health impacts of Chernobyl. This paper summarises the findings relating to cancer. A dramatic increase in the incidence of thyroid cancer has been observed among those exposed to radioactive iodines in childhood and adolescence in the most contaminated territories. Iodine deficiency may have increased the risk of developing thyroid cancer following exposure to radioactive iodines, while prolonged stable iodine supplementation in the years after exposure may reduce this risk. Although increases in rates of other cancers have been reported, much of these increases appear to be due to other factors, including improvements in registration, reporting and diagnosis. Studies are few, however, and have methodological limitations. Further, because most radiation-related solid cancers continue to occur decades after exposure and because only 20 years have passed since the accident, it is too early to evaluate the full radiological impact of the accident. Apart from the large increase in thyroid cancer incidence in young people, there are at present no clearly demonstrated radiation-related increases in cancer risk. This should not, however, be interpreted to mean that no increase has in fact occurred: based on the experience of other populations exposed to ionising radiation, a small increase in the relative risk of cancer is expected, even at the low to moderate doses received. Although it is expected that epidemiological studies will have difficulty identifying such a risk, it may nevertheless translate into a substantial number of radiation-related cancer cases in the future, given the very large number of individuals exposed.

WHO 1st Consultation on the Development of a Global Biodosimetry Laboratories Network for Radiation Emergencies (BioDoseNet)

Abstract Blakely, W. F., Carr, Z., Chu, M. C-M., Dayal-Drager, R., Fujimoto, K., Hopmeir, M., Kulka, U., Lillis-Hearne, P., Livingston, G. K., Lloyd, D. C., Maznyk, N., Perez, M. D. R., Romm, H., Takashima, Y., Voisin, P., Wilkins, R. C. and Yoshida, M. A. WHO 1st Consultation on the Development of a Global Biodosimetry Laboratories Network for Radiation Emergencies (BioDoseNet). Radiat. Res. 171, 127–139 (2009). The World Health Organization (WHO) held a consultation meeting at WHO Headquarters, Geneva, Switzerland, December 17–18, 2007, to develop the framework for a global biodosimetry network. The WHO network is envisioned to enable dose assessment using multiple methods [cytogenetics, electron paramagnetic resonance (EPR), radionuclide bioassays, etc.]; however, the initial discussion focused on the cytogenetic bioassay (i.e., metaphase-spread dicentric assay). Few regional cytogenetic biodosimetry networks have been established so far. The roles and resources available from United Nations (UN) agencies that provide international cooperation in biological dosimetry after radiological emergencies were reviewed. In addition, extensive reliance on the use of the relevant International Standards Organization (ISO) standards was emphasized. The results of a WHO survey of global cytogenetic biological dosimetry capability were reported, and while the survey indicates robust global capability, there was also a clear lack of global leadership and coordination. The expert group, which had a concentrated focus on cytogenetic biodosimetry, formulated the general scope and concept of operations for the development of a WHO global biodosimetry laboratory network for radiation emergencies (BioDoseNet). Follow-on meetings are planned to further develop technical details for this network.

First global consensus for evidence-based management of the hematopoietic syndrome resulting from exposure to ionizing radiation.

OBJECTIVE Hematopoietic syndrome (HS) is a clinical diagnosis assigned to people who present with ≥ 1 new-onset cytopenias in the setting of acute radiation exposure. The World Health Organization convened a panel of experts to evaluate the evidence and develop recommendations for medical countermeasures for the management of HS in a hypothetical scenario involving the hospitalization of 100 to 200 individuals exposed to radiation. The objective of this consultancy was to develop recommendations for treatment of the HS based upon the quality of evidence. METHODS English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to panel members before the meeting and updated during the meeting. Published case series and case reports of individuals with HS, published randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation (GRADE) system. In cases in which data were limited or incomplete, a narrative review of the observations was made. No randomized controlled trials of medical countermeasures have been completed for individuals with radiation-associated HS. The use of GRADE analysis of countermeasures for injury to hematopoietic tissue was restricted by the lack of comparator groups in humans. Reliance on data generated in nonirradiated humans and experimental animals was necessary. RESULTS Based upon GRADE analysis and narrative review, a strong recommendation was made for the administration of granulocyte colony-stimulating factor or granulocyte macrophage colony-stimulating factor and a weak recommendation was made for the use of erythropoiesis-stimulating agents or hematopoietic stem cell transplantation. CONCLUSIONS Assessment of therapeutic interventions for HS in humans exposed to nontherapeutic radiation is difficult because of the limits of the evidence.

Literature Review and Global Consensus on Management of Acute Radiation Syndrome Affecting Nonhematopoietic Organ Systems

OBJECTIVES The World Health Organization convened a panel of experts to rank the evidence for medical countermeasures for management of acute radiation syndrome (ARS) in a hypothetical scenario involving the hospitalization of 100 to 200 victims. The goal of this panel was to achieve consensus on optimal management of ARS affecting nonhematopoietic organ systems based upon evidence in the published literature. METHODS English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to conferees in advance of and updated during the meeting. Published case series and case reports of ARS, publications of randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation system. In cases in which data were limited or incomplete, a narrative review of the observations was made. RESULTS No randomized controlled trials of medical countermeasures have been completed for individuals with ARS. Reports of countermeasures were often incompletely described, making it necessary to rely on data generated in nonirradiated humans and in experimental animals. A strong recommendation is made for the administration of a serotonin-receptor antagonist prophylactically when the suspected exposure is >2 Gy and topical steroids, antibiotics, and antihistamines for radiation burns, ulcers, or blisters; excision and grafting of radiation ulcers or necrosis with intractable pain; provision of supportive care to individuals with neurovascular syndrome; and administration of electrolyte replacement therapy and sedatives to individuals with significant burns, hypovolemia, and/or shock. A strong recommendation is made against the use of systemic steroids in the absence of a specific indication. A weak recommendation is made for the use of fluoroquinolones, bowel decontamination, loperamide, and enteral nutrition, and for selective oropharyngeal/digestive decontamination, blood glucose maintenance, and stress ulcer prophylaxis in critically ill patients. CONCLUSIONS High-quality studies of therapeutic interventions in humans exposed to nontherapeutic radiation are not available, and because of ethical concerns regarding the conduct of controlled studies in humans, such studies are unlikely to emerge in the near future.

Thyroid Nodules, Polymorphic Variants in DNA Repair and RET-Related Genes, and Interaction with Ionizing Radiation Exposure from Nuclear Tests in Kazakhstan

Abstract Sigurdson, A. J., Land, C. E., Bhatti, P., Pineda, M., Brenner, A., Carr, Z., Gusev, B. I., Zhumadilov, Z., Simon, S. L., Bouville, A., Rutter, J. L., Ron, E. and Struewing, J. P. Thyroid Nodules, Polymorphic Variants in DNA Repair and RET-Related Genes, and Interaction with Ionizing Radiation Exposure from Nuclear Tests in Kazakhstan. Radiat. Res. 171, 77–88 (2009). Risk factors for thyroid cancer remain largely unknown except for ionizing radiation exposure during childhood and a history of benign thyroid nodules. Because thyroid nodules are more common than thyroid cancers and are associated with thyroid cancer risk, we evaluated several polymorphisms potentially relevant to thyroid tumors and assessed interaction with ionizing radiation exposure to the thyroid gland. Thyroid nodules were detected in 1998 by ultrasound screening of 2997 persons who lived near the Semipalatinsk nuclear test site in Kazakhstan when they were children (1949–1962). Cases with thyroid nodules (n = 907) were frequency matched (1:1) to those without nodules by ethnicity (Kazakh or Russian), gender and age at screening. Thyroid gland radiation doses were estimated from fallout deposition patterns, residence history and diet. We analyzed 23 polymorphisms in 13 genes and assessed interaction with ionizing radiation exposure using likelihood ratio tests (LRT). Elevated thyroid nodule risks were associated with the minor alleles of RET S836S (rs1800862, P = 0.03) and GFRA1 −193C>G (rs not assigned, P = 0.05) and decreased risk with XRCC1 R194W (rs1799782, P trend = 0.03) and TGFB1 T263I (rs1800472, P = 0.009). Similar patterns of association were observed for a small number of papillary thyroid cancers (n = 25). Ionizing radiation exposure to the thyroid gland was associated with significantly increased risk of thyroid nodules (age and gender adjusted excess odds ratio/Gy = 0.30, 95% CI 0.05–0.56), with evidence for interaction by genotype found for XRCC1 R194W (LRT P value = 0.02). Polymorphisms in RET signaling, DNA repair and proliferation genes may be related to risk of thyroid nodules, consistent with some previous reports on thyroid cancer. Borderline support for gene-radiation interaction was found for a variant in XRCC1, a key base excision repair protein. Other pathways such as genes in double-strand break repair, apoptosis and genes related to proliferation should also be pursued.

Ultrasound-Detected Thyroid Nodule Prevalence and Radiation Dose from Fallout

Abstract Land, C. E., Zhumadilov, Z., Gusev, B. I., Hartshorne, M. H., Wiest, P. W., Woodward, P. W., Crooks, L. A., Luckyanov, N. K., Fillmore, C. M., Carr, Z., Abisheva, G., Beck, H. L., Bouville, A., Langer, J., Weinstock, R., Gordeev, K. I., Shinkarev, S. M. and Simon, S. L. Ultrasound-Detected Thyroid Nodule Prevalence and Radiation Dose from Fallout. Radiat. Res. 169, 373–383 (2008). Settlements near the Semipalatinsk Test Site (SNTS) in northeastern Kazakhstan were exposed to radioactive fallout during 1949–1962. Thyroid disease prevalence among 2994 residents of eight villages was ascertained by ultrasound screening. Malignancy was determined by cytopathology. Individual thyroid doses from external and internal radiation sources were reconstructed from fallout deposition patterns, residential histories and diet, including childhood milk consumption. Point estimates of individual external and internal dose averaged 0.04 Gy (range 0–0.65) and 0.31 Gy (0–9.6), respectively, with a Pearson correlation coefficient of 0.46. Ultrasound-detected thyroid nodule prevalence was 18% and 39% among males and females, respectively. It was significantly and independently associated with both external and internal dose, the main study finding. The estimated relative biological effectiveness of internal compared to external radiation dose was 0.33, with 95% confidence bounds of 0.09–3.11. Prevalence of papillary cancer was 0.9% and was not significantly associated with radiation dose. In terms of excess relative risk per unit dose, our dose–response findings for nodule prevalence are comparable to those from populations exposed to medical X rays and to acute radiation from the Hiroshima and Nagasaki atomic bombings.

WHO-REMPAN for global health security and strengthening preparedness and response to radiation emergencies.

In response to the changing global environment and emerging new issues related to health security, the World Health Organization (WHO) is putting in place new tools for collective defense, such as the revised International Health Regulations (IHR) (2005). The new framework puts additional responsibilities on both Member States and WHO itself in order to effectively implement the IHR (2005) and react effectively in case of public health emergency events of any nature. Since its establishment in 1987, the Radiation Emergency Medical Preparedness and Assistance Network of WHO (WHO-REMPAN) has become an important asset for the organizations capacity to respond to radiation emergencies and to assist its Member States to strengthen their own response capacities. The paper describes in detail the framework for the WHOs role in preparedness and response to radiation emergencies, including Emergency Conventions and IHR (2005), and how the WHO-REMPAN, through its activities (i.e., technical guidelines development, training, education, research, and information sharing), provides a significant contribution to the organizations program of work towards achievement of the global health security goal.

World Health Organization’s International Radon Project

Following initial in vitro and in vivo studies and important studies of uranium miners, scientists have now completed impressive case-control studies of lung cancer risk from exposure to residential radon. Researchers have pooled these studies, in which all the information from the individual studies was reanalyzed. These pooled analyzes confirm that in the context of residential exposure, radon is now an established risk factor for lung cancer. Many of the initial uncertainties have been reduced, and health risk assessors are now confident that radon may contribute to as much as 10% of the total burden of lung cancer—that is, 2% of all cancers in the population, worldwide. To reduce residential radon lung cancer risk, national authorities must have methods and tools based on solid scientific evidence and sound public health policies. To meet these needs, the World Health Organization (WHO) has initiated the WHO International Radon Project. This three year project, to be implemented during the period 2005–2008, will include (1) a worldwide database on national residential radon levels, radon action levels, regulations, research institutions, and authorities; (2) public health guidance for awareness-raising and mitigation; and (3) an estimation of the global burden of disease (GDB) associated with radon exposure.

Long-term health implications of the chernobyl accident and relevant projects of the world health organization

The past two decades have witnessed dramatic changes in public health governance and international cooperation on the Chernobyl Nuclear Power Plant accident, especially after the end of the Cold War. The World Health Organization (WHO) has committed itself deeply to the public health issues around Chernobyl and has participated in various health projects such as health monitoring and cancer screening. WHO has also been engaged in research activities such as the Chernobyl Tissue Bank, in close collaboration with the Ministries of Health in Belarus, Russia, and Ukraine. In addition to the official report of the Chernobyl Forum “Health Expert Groups” in 2005, the task of WHO is to not only analyze and clarify the global burden of Chernobyl-related illness, but also to promote the well-being of the local residents who suffered chronic low-level radiation exposure from radiation fallout.

WHO's public health agenda in response to the Fukushima Daiichi nuclear accident.

The World Health Organization (WHO) has responded to the 2011 East-Japan earthquake and tsunami through the three levels of its decentralised structure. It has provided public health advice regarding a number of issues relating to protective measures, potassium iodide use, as well as safety of food and drinking water, mental health, travel, tourism, and trade. WHO is currently developing an initial health risk assessment linked to a preliminary evaluation of radiation exposure around the world from the Fukushima Daiichi nuclear accident. Lessons learned from this disaster are likely to help future emergency response to multi-faceted disasters.