Chromosome analysis in childhood cancer survivors and their offspring—No evidence for radiotherapy-induced persistent genomic instability

Abstract

Suggestions that the induction of genomic instability could play a role in radiation-induced carcinogenesis and heritable disease prompted the investigation of chromosome instability in relation to radiotherapy for childhood cancer. Chromosome analysis of peripheral blood lymphocytes at their first in vitro division was undertaken on 25 adult survivors of childhood cancer treated with radiation, 26 partners who acted as the non-irradiated control group and 43 offspring. A statistically significant increase in the frequency of dicentrics in the cancer survivor group compared with the partner control group was attributed to the residual effect of past radiation therapy. However, chromatid aberrations plus chromosome gaps, the aberrations most associated with persistent instability, were not increased. Therefore, there was no evidence that irradiation of the bone marrow had resulted in instability being transmitted to descendant cells. Frequencies of all aberration categories were significantly lower in the offspring group, compared to the partner group, apart from dicentrics for which the decrease did not reach statistical significance. The lower frequencies in the offspring provide no indication of transmissible instability being passed through the germline to the somatic cells of the offspring. Thus, in this study, genomic instability was not associated with radiotherapy in those who had received such treatment, nor was it found to be a transgenerational radiation effect.

Mortality among offspring of women diagnosed with cancer: A population‐based cohort study

“…14 Most studies report no chromosomal abnormalities, [20][21][22][23][24] malformations, 21,24-28 congenital defects 21 or cancer 29,30 in offspring of cancer survivors, with the exceptions of Dalberg et al 15 who noted an increased risk of malformation among women who conceived after treatment for breast cancer, Winther et al 28 who noted a small (not significantly increased) risk of malformations in children with a parent who received irradiation for childhood cancer and Stahl et al 27 who observed statistically significant but modestly increased risk of major congenital abnormalities among offspring of males with a history of cancer. In accordance with these previous publications, we observed an increased mortality risk in offspring of survivors of hematological cancer, a substantial part of whom will have received radiation therapy for (non) Hodgkin lymphoma.…”

Radiation-induced transgenerational alterations in genome stability and DNA damage

“…It should however be stressed that, to date, the issue of cancer predisposition among the nonexposed offspring of irradiated laboratory animals remains highly controversial (reviewed by Dubrova, 2003). Furthermore, it should be stressed that, to date, there has been little experimental evidence for transgenerational effects in humans, with some data showing the lack of chromosomal instability among the children of irradiated childhood cancer survivors (Tawn et al, 2005). Future work should address these important issues.…”

Intercellular Communication in Response to Radiation Induced Stress: Bystander Effects in Vitro and in Vivo and Their Possible Clinical Implications

“…Furthermore, increased mortality was related to single treatment course of X-rays because of this diseases (Smith & Doll, 1982). However, other studies performed in adults many years after radiotherapy in childhood haven't shown genetic instability (Tawn et al, 2005). Neither was it shown in persons having professional contact with radiation, who have suffered internal plutonium contamination at least 10 years previous to the study (Whitehouse and Tawn, 2001).…”