Apoptosis, ageing and cancer susceptibility

Camplejohn, Richard S.; Gilchrist, R; Easton, Douglas F.; McKenzie-Edwards, E; Barnes, David J.; Eccles, Diana; Ardern‐Jones, Audrey; Hodgson, SV; Duddy, P M; Eeles, Rosalind

doi:10.1038/sj.bjc.6600767

Cited by 38 publications

(34 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We have previously shown that there was no significant difference between apoptotic response to irradiation and chromosome radiosensitivity between newly diagnosed breast cancer cases and controls (Camplejohn et al, 1995(Camplejohn et al, , 2003. However, in line with these studies, we detected a decline in final induced apoptotic response with age in both patients and unaffected controls (Docherty et al, 2007).…”

Section: Discussionsupporting

confidence: 89%

Is telomere length in peripheral blood lymphocytes correlated with cancer susceptibility or radiosensitivity?

et al. 2007

View full text Add to dashboard Cite

Mean terminal restriction fragment (TRF) lengths in white blood cells (WBCs) have been previously found to be associated with breast cancer. To assess whether this marker could be used as a test for breast cancer susceptibility in women, TRF length was measured in 72 treated female breast cancer patients and 1696 unaffected female controls between the ages of 45 and 77 from the Twin Research Unit at St Thomas' Hospital, as well as 140 newly diagnosed breast cancer cases and 108 mammographically screened unaffected controls from Guy's Hospital. Mean TRF was also tested for correlation with chromosome radiosensitivity and apoptotic response in the Guy's Hospital patients. After adjusting for age, smoking and body mass index, there was no significant difference in TRF lengths between the treated breast cancer patients and unaffected controls (P ¼ 0.71). A positive correlation between ageadjusted apoptotic response and mean TRF in newly diagnosed untreated breast cancer patients (P ¼ 0.008) was identified but no significant difference in TRF lengths between breast cancer patients and unaffected controls was detected (P ¼ 0.53). This suggests that TRF lengths in WBC, is not a marker of breast cancer susceptibility and does not vary significantly between affected women before and after treatment.

show abstract

Section: Discussionsupporting

confidence: 89%

Is telomere length in peripheral blood lymphocytes correlated with cancer susceptibility or radiosensitivity?

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Given these findings the two zygosity groups were analysed together in terms of the relationship between age and AR. As illustrated in Figure 2, there was a clear negative correlation between AR and age (P ¼ 0.007), with a reduction in AR of 3% per decade of life, which is similar to that found in earlier studies (Camplejohn et al, 2003).…”

Section: Modelling and Statistical Analysissupporting

confidence: 77%

“…We have demonstrated previously that DNA-damage-induced AR of PBL is reduced with increasing age at a rate of around 3 -5% per decade of life in both normal controls and cancer patients (Camplejohn et al, 2003). However, a weakness in this earlier study was a relative paucity of normal individuals over 45 years of age.…”

contrasting

confidence: 47%

Heritability of DNA-damage-induced apoptosis and its relationship with age in lymphocytes from female twins

et al. 2006

Self Cite

View full text Add to dashboard Cite

Apoptosis is a physiological form of cell death important in normal processes such as morphogenesis and the functioning of the immune system. In addition, defects in the apoptotic process play a major role in a number of important areas of disease, such as autoimmune diseases and cancer. DNA-damage-induced apoptosis plays a vital role in the maintenance of genomic stability by the removal of damaged cells. Previous studies of the apoptotic response (AR) to radiation-induced DNA damage of lymphoid cells from individuals carrying germline TP53 mutations have demonstrated a defective AR compared with normal controls. We have also previously demonstrated that AR is reduced as individuals age. Results from the current study on 108 twins aged 18 -80 years confirm these earlier findings that the AR of lymphoid cells to DNA damage is significantly reduced with increasing age. In addition this twin study shows, for the first time, that DNA-damage-induced AR has a strong degree of heritability of 81% (95% confidence interval 67 -89%). The vital role of DNA-damage-induced apoptosis in maintaining genetic stability, its relationship with age and its strong heritability underline the importance of this area of biology and suggest areas for further study.

show abstract

“…The transcription of six different genes by p53 all reduced significantly, including genes involved in apoptosis, cell cycle arrest, and senescence, demonstrating the reproducibility of these data. These results provide a mechanism for the reduced apoptosis in cells from older individuals (27), which is a general phenomenon with a wide variety of tissues from several inbred strains of mice displaying the same result and several diverse stress signals all failing to activate p53 functions robustly. Interestingly, among the whole panel of tissues tested, including spleen, heart, lung, thymus, kidney, liver, and skin, spleen of aging C57BL/6 mice showed the most severe reduction in both levels of ATM mRNA expression and p53 protein accumulation in response to IR (data not shown), which could be one of the reasons why splenic lymphomas is the most frequent tumors observed in aging C57BL/6 mice.…”

Section: Discussionmentioning

confidence: 99%

Declining p53 function in the aging process: A possible mechanism for the increased tumor incidence in older populations

Feng

Teresky

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

248

198

View full text Add to dashboard Cite

Cancer is a disease of aging. The accumulation of mutations in individual cells over a lifetime is thought to be the reason. In this work, we explored an additional hypothesis: could p53 function decline with age, which would contribute to an enhanced mutation frequency and tumorigenesis in the aging process? The efficiency of the p53 response to ␥-irradiation was found to decline significantly in various tissues of aging mice from several inbred strains, including lower p53 transcriptional activity and p53-dependent apoptosis. This decline resulted from a decreased stabilization of the p53 protein after stress. The function of the Ataxia-telangiectasia mutated (ATM) kinase declined significantly with age, which may then be responsible for the decline of the p53 response to radiation. Declining p53 responses to other stresses were also observed in the cultured splenocytes from aging mice. Interestingly, the time of onset of this decreased p53 response correlated with the life span of mice; mice that live longer delay their onset of decreased p53 activity with time. These results suggest an enhanced fixation of mutations in older individuals because of the declining fidelity of p53-mediated apoptosis or senescence in response to stress, and they suggest a plausible explanation for the correlation between tumorigenesis and the aging process.apoptosis ͉ Ataxia-telangiectasia mutated (ATM) ͉ tumorigenesis

show abstract

Apoptosis, ageing and cancer susceptibility

Cited by 38 publications

References 11 publications

Is telomere length in peripheral blood lymphocytes correlated with cancer susceptibility or radiosensitivity?

Is telomere length in peripheral blood lymphocytes correlated with cancer susceptibility or radiosensitivity?

Heritability of DNA-damage-induced apoptosis and its relationship with age in lymphocytes from female twins

Declining p53 function in the aging process: A possible mechanism for the increased tumor incidence in older populations

Contact Info

Product

Resources

About