PMID- 33276807 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20210621 IS - 1465-542X (Electronic) IS - 1465-5411 (Print) IS - 1465-5411 (Linking) VI - 22 IP - 1 DP - 2020 Dec 4 TI - Telomere lengths in women treated for breast cancer show associations with chemotherapy, pain symptoms, and cognitive domain measures: a longitudinal study. PG - 137 LID - 10.1186/s13058-020-01368-6 [doi] LID - 137 AB - BACKGROUND: Survival rates for breast cancer (BC) have improved, but quality of life post-diagnosis/treatment can be adversely affected, with survivors reporting a constellation of psychoneurological symptoms (PNS) including stress, anxiety, depression, pain, fatigue, sleep disturbance, and cognitive dysfunction. METHODS: To assess a potential relationship between telomere length (TL) and the development/persistence of PNS, we longitudinally studied 70 women (ages 23-71) with early stage BC (I-IIIA) at 5 time-points: prior to treatment (baseline), the mid-point of their chemotherapy cycle, 6 months, 1 year, and 2 years following the initiation of chemotherapy. Measures quantified included assessments of each of the PNS noted above and TL [using both a multiplex qPCR assay and a chromosome-specific fluorescence in situ hybridization (FISH) assay]. RESULTS: Variables associated with qPCR mean TLs were age (p = 0.004) and race (T/S ratios higher in Blacks than Whites; p = 0.019). Significant differences (mostly decreases) in chromosome-specific TLs were identified for 32 of the 46 chromosomal arms at the mid-chemo time-point (p = 0.004 to 0.049). Unexpectedly, the sequential administration of doxorubicin [Adriamycin], cyclophosphamide [Cytoxan], and docetaxel [Taxotere] (TAC regimen) was consistently associated with higher TLs, when compared to TLs in women receiving a docetaxel [Taxotere], Carboplatin [Paraplatin], and trastuzumab [Herceptin] [TCH] chemotherapy regimen [association was shown with both the qPCR and FISH assays (p = 0.036)]. Of the PNS, pain was significantly negatively associated with TL (higher pain; shorter telomeres) for a subset of chromosomal arms (5q, 8p, 13p, 20p, 22p, Xp, Xq) (p = 0.014-0.047). Chromosomal TLs were also associated with 7 of the 8 cognitive domains evaluated, with the strongest relationship being noted for chromosome 17 and the visual memory domain (shorter telomeres; lower scores). CONCLUSIONS: We showed that race and age were significantly associated with telomere length in women treated for early stage BC and that acquired telomere alterations differed based on the woman's treatment regimen. Our study also demonstrated that pain and cognitive domain measures were significantly related to telomere values in this study cohort. Expanding upon the knowledge gained from this longitudinal study could provide insight about the biological cascade of events that contribute to PNS related to BC and/or its treatment. FAU - Alhareeri, Areej A AU - Alhareeri AA AD - Department of Human & Molecular Genetics, Virginia Commonwealth University, 737 North 5th Street, Biotech 8, Suite 104, Richmond, VA, 23129, USA. AD - King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. FAU - Archer, Kellie J AU - Archer KJ AD - Division of Biostatistics, The Ohio State University, Columbus, OH, USA. FAU - Fu, Han AU - Fu H AD - Division of Biostatistics, The Ohio State University, Columbus, OH, USA. FAU - Lyon, Debra E AU - Lyon DE AD - College of Nursing, University of Florida, Gainesville, FL, USA. FAU - Elswick, R K Jr AU - Elswick RK Jr AD - Family and Community Health Nursing, School of Nursing, Virginia Commonwealth University, Richmond, VA, USA. FAU - Kelly, Debra L AU - Kelly DL AD - College of Nursing, University of Florida, Gainesville, FL, USA. FAU - Starkweather, Angela R AU - Starkweather AR AD - University of Connecticut School of Nursing, Storrs, CT, USA. FAU - Elmore, Lynne W AU - Elmore LW AD - American Cancer Society, Atlanta, GA, USA. FAU - Bokhari, Yahya A AU - Bokhari YA AD - King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. FAU - Jackson-Cook, Colleen K AU - Jackson-Cook CK AUID- ORCID: 0000-0002-3261-909X AD - Department of Human & Molecular Genetics, Virginia Commonwealth University, 737 North 5th Street, Biotech 8, Suite 104, Richmond, VA, 23129, USA. colleen.jackson-cook@vcuhealth.org. AD - Department of Pathology, Virginia Commonwealth University, Richmond, VA, USA. colleen.jackson-cook@vcuhealth.org. AD - Member of the Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA. colleen.jackson-cook@vcuhealth.org. LA - eng GR - R01 NR012667/NR/NINR NIH HHS/United States GR - P30 CA016058/CA/NCI NIH HHS/United States PT - Journal Article PT - Observational Study PT - Research Support, N.I.H., Extramural DEP - 20201204 PL - England TA - Breast Cancer Res JT - Breast cancer research : BCR JID - 100927353 SB - IM MH - Adult MH - Age Factors MH - Aged MH - Aging/genetics MH - Antineoplastic Combined Chemotherapy Protocols/*adverse effects MH - Breast Neoplasms/diagnosis/*drug therapy MH - Cancer Survivors/psychology/statistics & numerical data MH - Cognitive Dysfunction/diagnosis/epidemiology/*genetics MH - Female MH - Humans MH - Karyotyping MH - Longitudinal Studies MH - Middle Aged MH - Pain/diagnosis/epidemiology/*genetics MH - Pain Measurement MH - Quality of Life MH - Telomere/metabolism MH - Telomere Homeostasis/*drug effects MH - Time Factors MH - Young Adult PMC - PMC7716505 OTO - NOTNLM OT - Breast cancer OT - Chemotherapy-related cognitive dysfunction OT - Chromosome-specific telomere lengths OT - Psychoneurologic symptoms OT - Telomere COIS- The authors declare that they have no competing interests. EDAT- 2020/12/06 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/12/04 CRDT- 2020/12/05 05:20 PHST- 2020/04/22 00:00 [received] PHST- 2020/11/08 00:00 [accepted] PHST- 2020/12/05 05:20 [entrez] PHST- 2020/12/06 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/12/04 00:00 [pmc-release] AID - 10.1186/s13058-020-01368-6 [pii] AID - 1368 [pii] AID - 10.1186/s13058-020-01368-6 [doi] PST - epublish SO - Breast Cancer Res. 2020 Dec 4;22(1):137. doi: 10.1186/s13058-020-01368-6.