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G(2) chromosomal radiosensitivity in Danish survivors of childhood and adolescent cancer and their offspring.

Curwen GB, Winther JF, Tawn EJ, Smart V, Whitehouse CA, Rees GS, Olsen JH, Guldberg P, Rechnitzer C, Schrøder H, Bryant PE, Sheng X, Lee HS, Chakraborty R, Boice JD - Br. J. Cancer (2005)

Bottom Line: 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).Heritability of the radiosensitive phenotype was examined by segregation analysis of the Danish families and suggested that 67.3% of the phenotypic variance of G(2) chromosomal radiosensitivity is attributable to a putative major gene locus with dominant effect.

View Article: PubMed Central - PubMed

Affiliation: Westlakes Research Institute, Moor Row, Cumbria CA24 3JY, UK. Gillian.Curwen@westlakes.ac.uk

ABSTRACT
In order to investigate the relationship between chromosomal radiosensitivity and early-onset cancer, the G(2) 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 G(2) 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 G(2) chromosomal radiosensitivity is attributable to a putative major gene locus with dominant effect.

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Related in: MedlinePlus

Distributions of G2 induced aberration frequencies in four groups of donors. The dotted and solid vertical lines represent the cutoff points for a normal and radiosensitive response, based on the 90th percentile of the WRI control and partner control groups, respectively.
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fig1: Distributions of G2 induced aberration frequencies in four groups of donors. The dotted and solid vertical lines represent the cutoff points for a normal and radiosensitive response, based on the 90th percentile of the WRI control and partner control groups, respectively.

Mentions: Distributions of aberration frequencies for the WRI control and three family groups are illustrated in Figure 1. Using the 90th percentile cutoff point for the WRI control group of 122 aberrations per 100 cells for a radiosensitive/non-radiosensitive response, the proportion of individuals with elevated G2 radiosensitivity was 11, 35, 52 and 53% for the WRI control, partner control, cancer survivor and the offspring groups, respectively. While the difference between the WRI control group and the partner control group did not reach statistical significance (P=0.084), significant differences were found between the WRI control group and the cancer survivor group (P=0.002) and the WRI control group and the offspring group (P<0.001). However, when the 90th percentile value of 160 aberrations per 100 cells for the partner control group was used as the cutoff point for increased radiosensitivity, 13, 4 and 18% of the partner control, cancer survivor and offspring groups, respectively, were classified radiosensitive, while no individual from the WRI control group displayed enhanced radiosensitivity. Using the partner control group to define the radiosensitivity cutoff point resulted in no significant differences in the proportion of sensitive individuals between the partner control group and either the cancer survivor group (P=0.608) or the offspring group (P=0.729).


G(2) chromosomal radiosensitivity in Danish survivors of childhood and adolescent cancer and their offspring.

Curwen GB, Winther JF, Tawn EJ, Smart V, Whitehouse CA, Rees GS, Olsen JH, Guldberg P, Rechnitzer C, Schrøder H, Bryant PE, Sheng X, Lee HS, Chakraborty R, Boice JD - Br. J. Cancer (2005)

Distributions of G2 induced aberration frequencies in four groups of donors. The dotted and solid vertical lines represent the cutoff points for a normal and radiosensitive response, based on the 90th percentile of the WRI control and partner control groups, respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361675&req=5

fig1: Distributions of G2 induced aberration frequencies in four groups of donors. The dotted and solid vertical lines represent the cutoff points for a normal and radiosensitive response, based on the 90th percentile of the WRI control and partner control groups, respectively.
Mentions: Distributions of aberration frequencies for the WRI control and three family groups are illustrated in Figure 1. Using the 90th percentile cutoff point for the WRI control group of 122 aberrations per 100 cells for a radiosensitive/non-radiosensitive response, the proportion of individuals with elevated G2 radiosensitivity was 11, 35, 52 and 53% for the WRI control, partner control, cancer survivor and the offspring groups, respectively. While the difference between the WRI control group and the partner control group did not reach statistical significance (P=0.084), significant differences were found between the WRI control group and the cancer survivor group (P=0.002) and the WRI control group and the offspring group (P<0.001). However, when the 90th percentile value of 160 aberrations per 100 cells for the partner control group was used as the cutoff point for increased radiosensitivity, 13, 4 and 18% of the partner control, cancer survivor and offspring groups, respectively, were classified radiosensitive, while no individual from the WRI control group displayed enhanced radiosensitivity. Using the partner control group to define the radiosensitivity cutoff point resulted in no significant differences in the proportion of sensitive individuals between the partner control group and either the cancer survivor group (P=0.608) or the offspring group (P=0.729).

Bottom Line: 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).Heritability of the radiosensitive phenotype was examined by segregation analysis of the Danish families and suggested that 67.3% of the phenotypic variance of G(2) chromosomal radiosensitivity is attributable to a putative major gene locus with dominant effect.

View Article: PubMed Central - PubMed

Affiliation: Westlakes Research Institute, Moor Row, Cumbria CA24 3JY, UK. Gillian.Curwen@westlakes.ac.uk

ABSTRACT
In order to investigate the relationship between chromosomal radiosensitivity and early-onset cancer, the G(2) 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 G(2) 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 G(2) chromosomal radiosensitivity is attributable to a putative major gene locus with dominant effect.

Show MeSH
Related in: MedlinePlus