Apoptosis, ageing and cancer susceptibility

Camplejohn, R.S., Gilchrist, R., Easton, D., McKenzie-Edwards, E., Barnes, D.M., Eccles, D.M., Ardern-Jones, A., Hodgson, S.V., Duddy, P.M. and Eeles, R.A. (2003) Apoptosis, ageing and cancer susceptibility. British Journal of Cancer, 88 (4), 487-490. (doi:10.1038/sj.bjc.6600767).

Abstract

We have previously shown that peripheral blood lymphocytes (PBL) from individuals carrying a germline TP53 mutation show a dramatically reduced apoptotic response to radiation. As part of a study of this phenomenon, we also investigated apoptotic response in a series of breast cancer patients lacking TP53 mutations and in a control group of individuals without cancer. There was a significant reduction in mean apoptotic response with increasing age in all groups. These findings are consistent with a number of studies in rodents, which have demonstrated a reduction in DNA damage-induced apoptosis with increasing age. In addition, after adjusting for age, breast cancer patients showed significantly reduced apoptotic responses compared with normal controls (P=0.002). The odds ratio for breast cancer in women with an apoptotic response of <35%, compared with women with a response of >49%, was 6.42 (95% CI 1.68-24.6). The data further support the hypothesis that a reduction in apoptotic response to DNA damage with increasing age may play a significant role in the age-related increase in cancer.

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Contributors

Author: D.M. Eccles

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