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


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.


CONCLUSIONS
An association between G(2) 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.
Curwen
Gillian B
GB
Westlakes Research Institute, Westlakes Science and Technology Park, Moor Row, Cumbria, UK. gillian.curwen@gmail.com
Cadwell
Kevin K
KK
Winther
Jeanette F
JF
Tawn
E Janet
EJ
Rees
Gwen S
GS
Olsen
Jørgen H
JH
Rechnitzer
Catherine
C
Schroeder
Henrik
H
Guldberg
Per
P
Cordell
Heather J
HJ
Boice
John D
JD
D000328:Adult; D032721:Adult Children; D002877:Chromosomes, Human / Q000235:genetics / Q000502:physiology / Q000528:radiation effects*; D003718:Denmark / Q000453:epidemiology; D004307:Dose-Response Relationship, Radiation; D016195:G2 Phase / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics / Q000502:physiology / Q000528:radiation effects*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000235:genetics / Q000502:physiology / Q000528:radiation effects*; D017741:Survivors; D013997:Time Factors; D014964:X-Ray Therapy / Q000009:adverse effects*
Am J Hum Genet. 1998 May;62(5):1198-211
9545414
Am J Hum Genet. 1999 Sep;65(3):784-94
10441587
Mutat Res. 1998 Jul 17;403(1-2):177-83
9726018
Br J Cancer. 2002 Dec 2;87(12):1379-85
12454765
Mutat Res. 2005 Dec 30;592(1-2):6-17
15990124
J Carcinog. 2005 Jan 17;4(1):2
15652000
Radiat Res. 2002 Apr;157(4):472-7
11893251
Br J Cancer. 2001 Apr 6;84(7):892-6
11286467
Mutat Res. 2003 Jul 25;528(1-2):105-10
12873728
Int J Radiat Biol. 2002 May;78(5):341-6
12020425
Int J Radiat Biol. 2002 Sep;78(9):863-6
12428927
Radiat Res. 1996 Jan;145(1):3-16
8532833
Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4):1245-52
17145539
Health Phys. 2003 Jul;85(1):65-80
12852473
Br J Cancer. 2005 Oct 31;93(9):1038-45
16234827
Int J Radiat Biol. 1999 Jan;75(1):1-10
9972785
Toxicol Lett. 2004 Apr 1;149(1-3):345-52
15093280
Environ Health Perspect. 1997 Dec;105 Suppl 6:1467-71
9467065
Lancet. 1994 Nov 19;344(8934):1444
7968110
Br J Cancer. 2008 May 20;98(10):1723-38
18414410
Br J Cancer. 2001 Mar 23;84(6):776-82
11259091
Cytogenet Genome Res. 2004;104(1-4):365-70
15162066
Mutat Res. 2005 Oct 15;578(1-2):308-16
16005910
Strahlenther Onkol. 2000 May;176(5):229-34
10847120
Int J Radiat Biol. 2005 May;81(5):373-8
16076752
Br J Cancer. 2001 Oct 19;85(8):1157-61
11710829