Inherited susceptibility to bleomycin-induced chromatid breaks in cultured peripheral blood lymphocytes.
BACKGROUND
Susceptibility to bleomycin-induced chromatid breaks in cultured peripheral blood lymphocytes may reflect the way a person deals with carcinogenic challenges. This susceptibility (also referred to as mutagen sensitivity) has been found to be increased in patients with environmentally related cancers, including cancers of the head and neck, lung, and colon, and, in combination with carcinogenic exposure, this susceptibility can greatly influence cancer risk. The purpose of this study was to assess the heritability of mutagen sensitivity.


METHODS
Heritability was determined by use of a maximum likelihood method that employed the FISHER package of pedigree analysis. Bleomycin-induced breaks per cell values for 135 healthy volunteers without cancer were determined. These individuals were from 53 different pedigrees and included 25 monozygotic twin pairs (n = 50), 14 pairs of dizygotes (twin pairs and siblings, n = 28), and 14 families selected on the basis of a first-degree relative who was successfully treated for head and neck cancer and who had no sign of recurrence for at least 1 year. All data were analyzed simultaneously, and different models of familial resemblance were fitted to the data. All P values are two-sided.


RESULTS
Our results showed no evidence for the influence of a shared family environment on bleomycin-induced chromatid breaks. Genetic influences, however, were statistically significant (P =. 036) and accounted for 75% of the total variance.


CONCLUSIONS
The high heritability estimate of the susceptibility to bleomycin-induced chromatid breaks indicates a clear genetic basis. The findings of this study support the notion that a common genetic susceptibility to DNA damage--and thereby a susceptibility to cancer--may exist in the general population.
Cloos
J
J
J. Cloos, E. J.C. Nieuwenhuis,M. L.T. van der Sterre, G. B. Snow, B. J. M. Braakhuis, Department of Otolaryngology/Head and Neck Surgery, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Nieuwenhuis
E J
EJ
Boomsma
D I
DI
Kuik
D J
DJ
van der Sterre
M L
ML
Arwert
F
F
Snow
G B
GB
Braakhuis
B J
BJ
D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D001761:Bleomycin / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002478:Cells, Cultured; D002842:Chromatids / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D009153:Mutagens / Q000009:adverse effects*; D012016:Reference Values; D014838:Volunteers
D000964:Antimetabolites, Antineoplastic; D009153:Mutagens; D001761:Bleomycin