Apoptosis, ageing and cancer susceptibility

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.

Figure 1

The above graph plots mean radiation-induced apoptosis as a percentage of total PBL in a control group (solid line, n=6), a group of general breast cancer patients (dashed line, n=5) and, for comparison, a group of LFS/LFL TP53 mutation carriers (thick dashed line, n=6). Error bars show the s.e. between each data measurement.