7 research outputs found
Biomarkers of aging associated with past treatments in breast cancer survivors.
Radiation and chemotherapy are effective treatments for cancer, but are also toxic to healthy cells. Little is known about whether prior exposure to these treatments is related to markers of cellular aging years later in breast cancer survivors. We examined whether past exposure to chemotherapy and/or radiation treatment was associated with DNA damage, telomerase activity, and telomere length 3-6 years after completion of primary treatments in breast cancer survivors (stage 0-IIIA breast cancer at diagnosis). We also examined the relationship of these cellular aging markers with plasma levels of Interleukin (IL)-6, soluble TNF-receptor-II (sTNF-RII), and C-reactive protein (CRP). Ninety-four women (36.4-69.5 years; 80% white) were evaluated. Analyses adjusting for age, race, BMI, and years from last treatment found that women who had prior exposure to chemotherapy and/or radiation compared to women who had previously received surgery alone were more likely to have higher levels of DNA damage (P = .02) and lower telomerase activity (P = .02), but did not have differences in telomere length. More DNA damage and lower telomerase were each associated with higher levels of sTNF-RII (P's < .05). We found that exposure to chemotherapy and/or radiation 3-6 years prior was associated with markers of cellular aging, including higher DNA damage and lower telomerase activity, in post-treatment breast cancer survivors. Furthermore, these measures were associated with elevated inflammatory activation, as indexed by sTNF-RII. Given that these differences were observed many years after the treatment, the findings suggest a long lasting effect of chemotherapy and/or radiation exposure
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Cognitive performance in survivors of breast cancer and markers of biological aging.
BackgroundBiological aging pathways accelerated by cancer treatments may be a mechanism for cognitive impairment in cancer survivors. The goal of the current study was to examine whether indicators of biological aging, namely elevated levels of DNA damage, reduced telomerase enzymatic activity, and shorter peripheral blood mononuclear cell (PBMC) telomere length (TL) would be related to cognitive function in a cohort of survivors of breast cancer.MethodsThe authors evaluated a cross-sectional sample of 94 women aged 36 to 69 years who were treated for early-stage breast cancer 3 to 6 years previously. Leukocyte DNA damage, PBMC telomerase enzymatic activity, PBMC TL, and the inflammatory marker soluble tumor necrosis factor receptor II (sTNF-RII) were determined from blood samples. Cognitive function was assessed using a neuropsychological test battery and self-report. Linear regression models examined the relationship between biological aging predictors and cognitive outcomes.ResultsBoth higher DNA damage and lower telomerase were found to be statistically significantly related to lower executive function scores adjusting for age, body mass index, race, years from treatment, and intelligence score (standardized coefficients [B], -0.23 and 0.30; all P values <.05). In addition, lower telomerase activity was associated with worse attention and motor speed scores (B values, 0.30 and 0.24; P <.05). sTNF-RII and TL were found to be unrelated to any of the neurocognitive domains.ConclusionsThe results of the current study suggest a significant association between measures of biological aging and objective measures of cognitive performance in survivors of breast cancer. Future prospective studies are needed to confirm a causal role of biological aging as a driver of declines in cognitive function after cancer treatment
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Cognitive performance in survivors of breast cancer and markers of biological aging.
BackgroundBiological aging pathways accelerated by cancer treatments may be a mechanism for cognitive impairment in cancer survivors. The goal of the current study was to examine whether indicators of biological aging, namely elevated levels of DNA damage, reduced telomerase enzymatic activity, and shorter peripheral blood mononuclear cell (PBMC) telomere length (TL) would be related to cognitive function in a cohort of survivors of breast cancer.MethodsThe authors evaluated a cross-sectional sample of 94 women aged 36 to 69 years who were treated for early-stage breast cancer 3 to 6 years previously. Leukocyte DNA damage, PBMC telomerase enzymatic activity, PBMC TL, and the inflammatory marker soluble tumor necrosis factor receptor II (sTNF-RII) were determined from blood samples. Cognitive function was assessed using a neuropsychological test battery and self-report. Linear regression models examined the relationship between biological aging predictors and cognitive outcomes.ResultsBoth higher DNA damage and lower telomerase were found to be statistically significantly related to lower executive function scores adjusting for age, body mass index, race, years from treatment, and intelligence score (standardized coefficients [B], -0.23 and 0.30; all P values <.05). In addition, lower telomerase activity was associated with worse attention and motor speed scores (B values, 0.30 and 0.24; P <.05). sTNF-RII and TL were found to be unrelated to any of the neurocognitive domains.ConclusionsThe results of the current study suggest a significant association between measures of biological aging and objective measures of cognitive performance in survivors of breast cancer. Future prospective studies are needed to confirm a causal role of biological aging as a driver of declines in cognitive function after cancer treatment
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Biomarkers of aging associated with past treatments in breast cancer survivors.
Radiation and chemotherapy are effective treatments for cancer, but are also toxic to healthy cells. Little is known about whether prior exposure to these treatments is related to markers of cellular aging years later in breast cancer survivors. We examined whether past exposure to chemotherapy and/or radiation treatment was associated with DNA damage, telomerase activity, and telomere length 3-6 years after completion of primary treatments in breast cancer survivors (stage 0-IIIA breast cancer at diagnosis). We also examined the relationship of these cellular aging markers with plasma levels of Interleukin (IL)-6, soluble TNF-receptor-II (sTNF-RII), and C-reactive protein (CRP). Ninety-four women (36.4-69.5 years; 80% white) were evaluated. Analyses adjusting for age, race, BMI, and years from last treatment found that women who had prior exposure to chemotherapy and/or radiation compared to women who had previously received surgery alone were more likely to have higher levels of DNA damage (P = .02) and lower telomerase activity (P = .02), but did not have differences in telomere length. More DNA damage and lower telomerase were each associated with higher levels of sTNF-RII (P's < .05). We found that exposure to chemotherapy and/or radiation 3-6 years prior was associated with markers of cellular aging, including higher DNA damage and lower telomerase activity, in post-treatment breast cancer survivors. Furthermore, these measures were associated with elevated inflammatory activation, as indexed by sTNF-RII. Given that these differences were observed many years after the treatment, the findings suggest a long lasting effect of chemotherapy and/or radiation exposure