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Apoptosis, ageing and cancer susceptibility
R S Camplejohn1, R Gilchrist, D Easton
1Richard 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
British Journal of Cancer
|February 20, 2003
Summary
Reduced apoptosis, or programmed cell death, in peripheral blood lymphocytes (PBL) is linked to aging and breast cancer risk. Lower apoptotic response significantly increases the odds of developing breast cancer.
Area of Science:
- Cell Biology
- Oncology
- Genetics
Background:
- Germline TP53 mutations reduce lymphocyte apoptotic response to radiation.
- Aging is associated with reduced DNA damage-induced apoptosis in rodents.
- Investigated apoptotic response in breast cancer patients and controls.
Purpose of the Study:
- To examine the relationship between age, TP53 status, and apoptotic response to DNA damage.
- To determine if reduced apoptotic response is a risk factor for breast cancer.
Main Methods:
- Assessed apoptotic response in peripheral blood lymphocytes (PBL) from breast cancer patients and controls.
- Analyzed the impact of age on apoptotic response across all groups.
- Compared apoptotic responses between breast cancer patients and normal controls, adjusting for age.
Main Results:
- Mean apoptotic response significantly decreased with increasing age in all study groups.
- Breast cancer patients exhibited significantly reduced apoptotic responses compared to controls, even after age adjustment (P=0.002).
- Women with low apoptotic response (<35%) had a 6.42-fold increased odds of breast cancer compared to those with high response (>49%).
Conclusions:
- Reduced apoptotic response to DNA damage correlates with increasing age.
- Diminished apoptotic response is a significant risk factor for breast cancer.
- Age-related decline in apoptosis may contribute to the increased incidence of cancer with age.