TY - JOUR
T1 - G2 chromosomal radiosensitivity in Danish survivors of childhood and adolescent cancer and their offspring
AU - Curwen, G. B.
AU - Winther, J. F.
AU - Tawn, E. J.
AU - Smart, V.
AU - Whitehouse, C. A.
AU - Rees, G. S.
AU - Olsen, J. H.
AU - Guldberg, P.
AU - Rechnitzer, C.
AU - Schrøder, H.
AU - Bryant, P. E.
AU - Sheng, X.
AU - Lee, H. S.
AU - Chakraborty, R.
AU - Boice, J. D.
PY - 2005/10/31
Y1 - 2005/10/31
N2 - In order to investigate the relationship between chromosomal radiosensitivity and early-onset cancer, the G2 chromosomal radiosensitivity assay was undertaken on a group of 23 Danish survivors of childhood and adolescent cancer, a control group comprising their partners and a group of 38 of their offspring. In addition, the previously reported in-house control group from Westlakes Research Institute (WRI) was extended to 27 individuals. When using the 90th percentile cutoff for the WRI control group, the proportion of individuals with elevated radiosensitivity was 11, 35, 52 and 53% for the WRI control, partner control, cancer survivor and the offspring groups, respectively, with significant differences between the WRI control group and the cancer survivor group (P=0.002) and the offspring group (P<0.001). However, while the comparisons with the WRI control group support an association of chromosomal radiosensitivity with cancer predisposition, when the partner control group was used to define the radiosensitivity cutoff point, no significant differences in radiosensitivity profiles were found between the partner control group and either the cancer survivor group or the offspring group. The failure to distinguish between the G2 aberration profiles of the apparently normal group of partners and the cancer survivor group suggests that any association with cancer should be viewed with caution, but also raises questions as to the suitability of the partners of cancer survivors to act as an appropriate control group. Heritability of the radiosensitive phenotype was examined by segregation analysis of the Danish families and suggested that 67.3% of the phenotypic variance of G2 chromosomal radiosensitivity is attributable to a putative major gene locus with dominant effect.
AB - In order to investigate the relationship between chromosomal radiosensitivity and early-onset cancer, the G2 chromosomal radiosensitivity assay was undertaken on a group of 23 Danish survivors of childhood and adolescent cancer, a control group comprising their partners and a group of 38 of their offspring. In addition, the previously reported in-house control group from Westlakes Research Institute (WRI) was extended to 27 individuals. When using the 90th percentile cutoff for the WRI control group, the proportion of individuals with elevated radiosensitivity was 11, 35, 52 and 53% for the WRI control, partner control, cancer survivor and the offspring groups, respectively, with significant differences between the WRI control group and the cancer survivor group (P=0.002) and the offspring group (P<0.001). However, while the comparisons with the WRI control group support an association of chromosomal radiosensitivity with cancer predisposition, when the partner control group was used to define the radiosensitivity cutoff point, no significant differences in radiosensitivity profiles were found between the partner control group and either the cancer survivor group or the offspring group. The failure to distinguish between the G2 aberration profiles of the apparently normal group of partners and the cancer survivor group suggests that any association with cancer should be viewed with caution, but also raises questions as to the suitability of the partners of cancer survivors to act as an appropriate control group. Heritability of the radiosensitive phenotype was examined by segregation analysis of the Danish families and suggested that 67.3% of the phenotypic variance of G2 chromosomal radiosensitivity is attributable to a putative major gene locus with dominant effect.
KW - Childhood and adolescent cancer
KW - Chromosomal radiosensitivity
KW - Inherited predisposition
UR - http://www.scopus.com/inward/record.url?scp=27644479261&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6602807
DO - 10.1038/sj.bjc.6602807
M3 - Article
C2 - 16234827
AN - SCOPUS:27644479261
SN - 0007-0920
VL - 93
SP - 1038
EP - 1045
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 9
ER -