Relationship of Genetic Differences to the Development of Chromosome Abnormalities

Germline Genetic Variation and Risk of Chromosome Aberrations Among Mayak Nuclear Workers

This is a collaborative study by the National Cancer Institute, Columbia University, and the Southern Urals Biophysics Institute in Russia. It will examine the relationship of differences in certain genes to the development of chromosomal abnormalities in workers at the Mayak nuclear production plant in Ozyorsk, Russia. This population was exposed to higher radiation doses from external and internal sources than those received by their counterparts in other countries or considered permissible today. If a risk relationship is found between genetic differences and chromosome abnormalities, the information might be useful in studies designed to examine how high radiation exposures cause cancer.

Radiation-exposed Mayak workers employed from 1948 to 1972 in the three Ozyorsk plants directly related to nuclear weapons production may be eligible for this study. They must have remained local residents in the area and estimates of their external and internal radiation exposures must be available.

Participants provide a blood sample for genetic studies and answer a questionnaire that includes demographic information and information about their family health history, history of benign tumors, if any, and history of smoking and alcohol consumption. Additional information is collected from patients' medical records.

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Study Overview

• Status: Terminated
• Conditions: Radiation Exposure

Detailed Description

Greater understanding of the role of individual variation in response to radiation exposure might clarify the inconsistent relationship between radiation dose, intermediate markers of induced DNA damage, and subsequent cancer risk. REB proposes to collaborate with Columbia University and the Southern Urals Biophysics Institute to elucidate the contribution of germline genetic variation to the frequency of chromosomal aberrations in a cohort of Russian nuclear workers with notable and atypical radiation exposures. Our collaborators are utilizing a new biodosimetry method, termed mBAND, to measure intra-chromosomal aberrations, a potentially useful biomarker of exposure to high linear energy transfer radiation such as plutonium. In addition, they will assess inter-chromosomal aberrations using mFISH (multicolor fluorescent insitu hybridization). As factors other than radiation dose may influence aberration frequency, REB proposes to add to this DOE-funded study an investigation of germline genetic variation in DNA repair and other genes in relation to aberration risk. Mayak nuclear workers (n = approximately 350) employed from 1948-72 will receive a short questionnaire and have a blood sample drawn while receiving routine annual medical exams. Germline genotype will be assessed as a risk factor for chromosome aberration frequency. In this study, we have the opportunity to address scientific questions regarding radiation carcinogenesis mechanisms at relatively little cost in a population with rare, higher dose exposures.

• Study Type: Observational
• Enrollment (Actual): 361

Contacts and Locations

Study Locations

• Russian Federation
  • Ozyorsk, Russian Federation
    • Southern Urals Biophysics Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• INCLUSION CRITERIA - EXPOSED POPULATION:

Individuals eligible to be included in the 'exposed' population include all those employed from 1948-1972 in the three plants directly related to nuclear-weapon production (nuclear reactor, radiochemical production plant, plutonium production plant), who have remained local residents, and who have estimates of their external gamma dose and internal plutonium exposure.

Some eligible workers did not have any plutonium exposure, but are still eligible to be included in the exposed sample due to their external radiation exposure.

All participants are required to be cancer-free at the time of enrollment.

EXCLUSION CRITERIA - EXPOSED POPULATION:

Individuals who have a medical history of radiation therapy or a blood transfusion within the previous year will be excluded.

As the sample size would not be adequate to examine their risk separately, Tartars and Bashkirs will not be included in the study.

INCLUSION CRITERIA - COMPARISON GROUP:

The comparison population will be drawn from current and former workers in the auxiliary plants (water treatment facility and mechanical repair plant) at the Mayak facility.

Included will be a stratified random sample of these workers who were employed from 1948-1972, who have remained local residents, and who have estimates of their external gamma dose.

Individuals selected will be frequency-matched according to age (5 year age groups) and gender to the exposed worker population.

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Bonassi S, Hagmar L, Stromberg U, Montagud AH, Tinnerberg H, Forni A, Heikkila P, Wanders S, Wilhardt P, Hansteen IL, Knudsen LE, Norppa H. Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. European Study Group on Cytogenetic Biomarkers and Health. Cancer Res. 2000 Mar 15;60(6):1619-25.
• Cardis E, Gilbert ES, Carpenter L, Howe G, Kato I, Armstrong BK, Beral V, Cowper G, Douglas A, Fix J, et al. Effects of low doses and low dose rates of external ionizing radiation: cancer mortality among nuclear industry workers in three countries. Radiat Res. 1995 May;142(2):117-32.
• Dupont WD, Plummer WD Jr. Power and sample size calculations for studies involving linear regression. Control Clin Trials. 1998 Dec;19(6):589-601. doi: 10.1016/s0197-2456(98)00037-3.

Study record dates

Study Major Dates

• Study Start: June 9, 2004
• Study Completion: September 17, 2014

Study Registration Dates

• First Submitted: June 1, 2007
• First Submitted That Met QC Criteria: June 1, 2007
• First Posted (Estimate): June 4, 2007

Study Record Updates

• Last Update Posted (Actual): December 17, 2019
• Last Update Submitted That Met QC Criteria: December 14, 2019
• Last Verified: September 17, 2014

More Information

Terms related to this study

• Keywords: Polymorphism; Russia; Ionizing Radiation; Plutonium; Biological Marker
• Other Study ID Numbers: 999904215; 04-C-N215