Chromosomal radiosensitivity in young cancer patients: possible evidence of genetic predisposition.
OBJECTIVE
To investigate the G2 chromosomal radiosensitivity of patients with cancers diagnosed when the patients are less than 20 years of age. Earlier studies demonstrated an enhanced sensitivity in substantial proportions of patients with breast or colorectal cancer, and in early onset head and neck cancer cases. Heritability of chromosomal radiosensitivity in families of breast cancer patients was also demonstrated. It is suggested that elevated sensitivity in this assay could be a marker of genetic predisposition to cancer, mediated through inherited genetic determinants of low penetrance.


METHODS
Stimulated lymphocytes were exposed to 0.5 Gy X-rays in the G2-phase of the cell cycle and chromatid aberrations were scored in metaphase cells.


RESULTS
The assay was performed on 32 patients with early onset cancers (aged 0.5-19 years) of various types and their sensitivity was compared with that of 41 young normal controls (0.25-19 years) and 32 adult normals (20-60 years). The proportion of cases showing enhanced sensitivity in the three groups was 44, 15 and 10%, respectively. The difference between the young patients and normals was highly significant (p = 0.004).


CONCLUSIONS
The results suggest the possibility that a substantial proportion of early onset cancers are associated with the inheritance of predisposing genes of low penetrance. However, support for this hypothesis requires that the heritability of chromosomal radiosensitivity be demonstrated in family members. In addition, a larger study is now required to investigate the chromosomal radiosensitivity of specific early onset cancers.
Baria
K
K
Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, M20 4BX, UK.
Warren
C
C
Eden
O B
OB
Roberts
S A
SA
West
C M
CM
Scott
D
D
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics* / Q000528:radiation effects*; D005260:Female; D016195:G2 Phase; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008214:Lymphocytes / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*