Apoptosis, ageing and cancer susceptibility

• Published in: British journal of cancer Vol. 88; no. 4; pp. 487 - 490
• Main Authors: 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, Eeles, R A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.02.2003; Nature Publishing Group
• Subjects: Adult; Age; Aging - physiology; Apoptosis; Apoptosis - radiation effects; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; BRCA1 Protein - genetics; BRCA2 Protein - genetics; Breast cancer; Cancer Research; Clinical; Disease Susceptibility; DNA damage; Dose-Response Relationship, Radiation; Drug Resistance; Epidemiology; Female; Gamma Rays; Genetics; Hospitals; Humans; Lymphocytes; Lymphocytes - pathology; Lymphocytes - radiation effects; Male; Medical research; Medical sciences; Middle Aged; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Mutation; Neoplasms - epidemiology; Neoplasms - genetics; Neoplasms - pathology; Odds Ratio; Oncology; Radiation; Sex Characteristics; Tumors; United Kingdom > UK; apoptosis; cancer susceptibility; radiation; age; Human; Senescence; Cell death; Ageing; Predisposition; Malignant tumor; Apoptosis
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6600767

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.