title: 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.
authors.affiliation: Richard Dimbleby Department of Cancer Research, Guy's, King's and St Thomas' School of Medicine, St Thomas' Hospital, London, UK. r.camplejohn@cancer.org.uk
authors.forename: R S
authors.initials: RS
authors.lastname: Camplejohn
authors.forename: R
authors.initials: R
authors.lastname: Gilchrist
authors.forename: D
authors.initials: D
authors.lastname: Easton
authors.forename: E
authors.initials: E
authors.lastname: McKenzie-Edwards
authors.forename: D M
authors.initials: DM
authors.lastname: Barnes
authors.forename: D M
authors.initials: DM
authors.lastname: Eccles
authors.forename: A
authors.initials: A
authors.lastname: Ardern-Jones
authors.forename: S V
authors.initials: SV
authors.lastname: Hodgson
authors.forename: P M
authors.initials: PM
authors.lastname: Duddy
authors.forename: R A
authors.initials: RA
authors.lastname: Eeles
mesh_terms: D000328:Adult; D000375:Aging / Q000502:physiology*; D017209:Apoptosis / Q000528:radiation effects; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D004198:Disease Susceptibility; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D006801:Humans; D008214:Lymphocytes / Q000473:pathology / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D016017:Odds Ratio; D012727:Sex Characteristics
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein