A Cytogenetic Assessment of British Nuclear Test Veterans and their Offspring

Project Organisation: Brunel University and the London School of Hygiene and Tropical Medicine
Project Cost: £450,070

Part of the team at the CHRC Brunel University London
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Project Activity
The project will identify cytogenetic alterations in cells sampled from British Nuclear Test Veterans which may provide evidence of previous and/or ongoing exposure to high-LET radiation and, to ascertain whether any acquired changes to the germline genome have been inherited by offspring. An identified cohort of 50 father-mother-child trio’s and matched control group will be identified and recruited to provide samples of blood and sperm (father), or blood only (mother and child). Samples will be assayed by a number of FISH-based techniques ascertaining (i) if there is any evidence of complex chromosome aberrations in BNTV fathers’ blood, (ii) if there is any evidence of elevated frequencies of chromosomal aberrations in the germline (sperm) of BNTV fathers, (iii) whether there is any cytogenetic evidence for genomic aberrations in the blood of BNTV offspring and (iv) to ascertain which parent any observed genetic abnormality was inherited or, whether it arose de novo.

Beneficiaries
Outcomes from this project will directly benefit participating families by providing them with the first comprehensive cytogenetic exploration to examine for possible differences between BNTV and control family groups. Importantly, this project will address the need that many respondents in the NTV Health Needs Analysis 2011 expressed; ‘access to cytogenetic testing’.

Knowledge gained from this project will make significant in-roads into clarifying on-going uncertainties about the possible impact on the future health of BNTV offspring and, will also inform the development of a larger-scale proposal. Accordingly outputs from this work will benefit the broader BNTV community and health professionals by providing a scientific rationale that will improve understanding and contribute to reducing the reported ‘anxiety and depression’ associated with the aforementioned uncertainties of BNTV members.

Progression & Future Activity
This project is seeking to address an ongoing concern within the nuclear test community whether veterans of nuclear testing programmes could have received sufficient radiation exposure to cause genetic damage (changes to the DNA). Veterans are concerned that this possible genetic damage may have increased their risk of developing various diseases. This concern extends to whether they might also have passed on genetic alterations to their children, thereby potentially affecting their family’s health.

Cytogenetic analysis at the CHRC
Cytogenetic analysis at the CHRC

To address these concerns Brunel University London and their collaborating partners, London School of Hygiene and Tropical Medicine are undertaking a cytogenetic (NCCF Phase 1) study. They are also undertaking a genetic (NCCF Phase 2) study in collaboration with the University of Leicester. These studies will compare the amount and type of genetic alterations found in a sample population of nuclear test veteran family trios (father, mother, and child) with that seen in veteran family trios who have no association with nuclear test participation. 

The project organisation successfully gained full Health Research Approval (HRA) in August 2017 after a lengthy process of ethical and legal scrutiny. This enabled the English and Welsh health board authorities to give their approvals for these studies to proceed with veterans who were in their jurisdiction. This in turn, allowed the process of recruitment of 50 test and 50 control family trios by informed consent to begin in January 2018. The recruitment process is complex and requires liaising with families’ GPs across the Country and, with individual families prior to obtaining their consent. However, good progress continues to be made and they have recruited more than half of the required participants. This is in-line with expectations based on the age of the veteran couples and our study requirement for complete trios.  

Blood samples are being received at Brunel University London and are being processed for cytogenetic (NCCF Phase 1) and genetic (NCCF Phase 2) analysis. In-depth analysis is underway and is continuing in parallel with ongoing recruitment to the study. To align the outputs of the NCCF Phase 1 Cytogenetics study with the NCCF Phase 2 Genetics study, The project organisation with the support of the NCCF requested and gained a no-cost extension to the term of the former study to the end of August 2020. 

Brunel University London will report their findings after the studies have been completed and have undergone the peer-review process for publication.

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