The heritability of G₂ chromosomal radiosensitivity and its association with cancer in Danish cancer survivors and their offspring

Abstract

Purpose: To investigate the relationship between chromosomal radiosensitivity and early-onset cancer under the age of 35 years and to examine the heritability of chromosomal radiosensitivity.

Materials and methods: Peripheral blood lymphocytes were cultured for 72 hours prior to being irradiated with 0.5 Gy, 300 kV X-rays. Colcemid was added to cultures 30 min post-irradiation. Cultures were harvested 90 min post-irradiation and analysed for chromatid gaps and breaks. Heritability was estimated using Sequential Oligogenic Linkage Analysis Routines (SOLAR) software and by segregation analysis.

Results: Elevated radiosensitivity was seen for seven out of 29 (24.1%) cancer survivors, three out of 29 (10.3%) partners and 10 out of 53 (20.8%) offspring. Although the proportion of individuals displaying enhanced radiosensitivity was twice as high in both the cancer survivor and offspring groups than the partner controls, neither reached statistical significance. Heritability analysis of the radiosensitive phenotype suggested 57.9–78.0% of the variance could be attributed to genetic factors.

Conclusion: An association between G₂ chromosomal radiosensitivity and childhood and young adult cancer is suggested but was not statistically significant. In contrast, there is strong evidence for heritability of the radiosensitive phenotype. The cancer survivors included a broad range of malignancies and future studies should focus on specific cancers with known or likely faults in deoxyribonucleic acid (DNA) damage recognition and repair mechanisms.

Keywords:

• chromosomal radiosensitivity
• heritability
• cancer

Acknowledgements

We thank the Danish families for agreeing to participate in this study and volunteering blood samples, Brian Møllgren, Rigshospitalet, for collection of blood samples from the families and the transport controls, Patricia Jonas, Newcastle NHS Trust, for collection of blood samples from the in-house assay control. Permissions were granted from the Danish Data Protection Agency (2001–41–1113) and the Danish Scientific Ethical Committee ([KF] 01 – 150/01, [KF] 11 – 129/02 and [H-KF] 01 – 150/01). This work was funded by a grant from the National Institutes of Health, USA (Grant Number 1 RO1 CA 104666) through Vanderbilt University Medical Center, USA. We are grateful for the support provided by the Danish Cancer Society. Some of the results of this paper were obtained by using the program package S.A.G.E., which is supported by a US Public Health Service Resource Grant (RR03655) from the National Center for Research Resources.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.