Apoptosis, ageing and cancer susceptibility.
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.
Camplejohn
R S
RS
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
Gilchrist
R
R
Easton
D
D
McKenzie-Edwards
E
E
Barnes
D M
DM
Eccles
D M
DM
Ardern-Jones
A
A
Hodgson
S V
SV
Duddy
P M
PM
Eeles
R A
RA
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
D019313:BRCA1 Protein; D024682:BRCA2 Protein