title: Inflammatory Cytokines and Comorbidity Development in Breast Cancer Survivors Versus Noncancer Controls: Evidence for Accelerated Aging?
abstract: Purpose The sequelae of cancer treatment may increase systemic inflammation and create a phenotype at increased risk of functional decline and comorbidities, leading to premature mortality. Little is known about how this trajectory compares with natural aging among peers of the same age without cancer. This longitudinal study investigated proinflammatory cytokines and comorbidity development over time among breast cancer survivors and a noncancer control group. Methods Women (N = 315; 209 with breast cancer and 106 in the control group) were recruited at the time of their work-up for breast cancer; they completed the baseline questionnaire, interview, and blood draw (lipopolysaccharide-stimulated production of interleukin [IL] -6, tumor necrosis factor-α, and IL-1β). Measures were repeated 6 and 18 months after primary cancer treatment (cancer survivors) or within a comparable time frame (control group). Results There were no baseline differences in comorbidities or cytokines between survivors and the control group. Over time, breast cancer survivors had significantly higher tumor necrosis factor-α and IL-6 compared with the control group. Survivors treated with surgery, radiation, and chemotherapy accumulated a significantly greater burden of comorbid conditions and suffered greater pain associated with inflammation over time after cancer treatment than did the control group. Conclusion Survivors who had multimodal treatment had higher cytokines and comorbidities, suggestive of accelerated aging. Comorbidities were related to inflammation in this sample, which could increase the likelihood of premature mortality. Given that many comorbidities take years to develop, future research with extended follow-up beyond 18 months is necessary to examine the evidence of accelerated aging in cancer survivors and to determine the responsible mechanisms.
authors.affiliation: Catherine M. Alfano, American Cancer Society, Washington, DC; Juan Peng, Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, Janice K. Kiecolt-Glaser, The Ohio State University College of Medicine; Rebecca R. Andridge, The Ohio State University College of Public Health; and Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, and Janice K. Kiecolt-Glaser, The Ohio State University, Columbus, OH.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Alfano
authors.affiliation: Catherine M. Alfano, American Cancer Society, Washington, DC; Juan Peng, Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, Janice K. Kiecolt-Glaser, The Ohio State University College of Medicine; Rebecca R. Andridge, The Ohio State University College of Public Health; and Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, and Janice K. Kiecolt-Glaser, The Ohio State University, Columbus, OH.
authors.forename: Juan
authors.initials: J
authors.lastname: Peng
authors.affiliation: Catherine M. Alfano, American Cancer Society, Washington, DC; Juan Peng, Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, Janice K. Kiecolt-Glaser, The Ohio State University College of Medicine; Rebecca R. Andridge, The Ohio State University College of Public Health; and Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, and Janice K. Kiecolt-Glaser, The Ohio State University, Columbus, OH.
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Andridge
authors.affiliation: Catherine M. Alfano, American Cancer Society, Washington, DC; Juan Peng, Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, Janice K. Kiecolt-Glaser, The Ohio State University College of Medicine; Rebecca R. Andridge, The Ohio State University College of Public Health; and Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, and Janice K. Kiecolt-Glaser, The Ohio State University, Columbus, OH.
authors.forename: Monica E
authors.initials: ME
authors.lastname: Lindgren
authors.affiliation: Catherine M. Alfano, American Cancer Society, Washington, DC; Juan Peng, Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, Janice K. Kiecolt-Glaser, The Ohio State University College of Medicine; Rebecca R. Andridge, The Ohio State University College of Public Health; and Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, and Janice K. Kiecolt-Glaser, The Ohio State University, Columbus, OH.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Povoski
authors.affiliation: Catherine M. Alfano, American Cancer Society, Washington, DC; Juan Peng, Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, Janice K. Kiecolt-Glaser, The Ohio State University College of Medicine; Rebecca R. Andridge, The Ohio State University College of Public Health; and Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, and Janice K. Kiecolt-Glaser, The Ohio State University, Columbus, OH.
authors.forename: Adele M
authors.initials: AM
authors.lastname: Lipari
authors.affiliation: Catherine M. Alfano, American Cancer Society, Washington, DC; Juan Peng, Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, Janice K. Kiecolt-Glaser, The Ohio State University College of Medicine; Rebecca R. Andridge, The Ohio State University College of Public Health; and Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, and Janice K. Kiecolt-Glaser, The Ohio State University, Columbus, OH.
authors.forename: Doreen M
authors.initials: DM
authors.lastname: Agnese
authors.affiliation: Catherine M. Alfano, American Cancer Society, Washington, DC; Juan Peng, Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, Janice K. Kiecolt-Glaser, The Ohio State University College of Medicine; Rebecca R. Andridge, The Ohio State University College of Public Health; and Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, and Janice K. Kiecolt-Glaser, The Ohio State University, Columbus, OH.
authors.forename: William B
authors.initials: WB
authors.lastname: Farrar
authors.affiliation: Catherine M. Alfano, American Cancer Society, Washington, DC; Juan Peng, Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, Janice K. Kiecolt-Glaser, The Ohio State University College of Medicine; Rebecca R. Andridge, The Ohio State University College of Public Health; and Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, and Janice K. Kiecolt-Glaser, The Ohio State University, Columbus, OH.
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Yee
authors.affiliation: Catherine M. Alfano, American Cancer Society, Washington, DC; Juan Peng, Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, Janice K. Kiecolt-Glaser, The Ohio State University College of Medicine; Rebecca R. Andridge, The Ohio State University College of Public Health; and Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, and Janice K. Kiecolt-Glaser, The Ohio State University, Columbus, OH.
authors.forename: William E
authors.initials: WE
authors.lastname: Carson
authors.affiliation: Catherine M. Alfano, American Cancer Society, Washington, DC; Juan Peng, Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, Janice K. Kiecolt-Glaser, The Ohio State University College of Medicine; Rebecca R. Andridge, The Ohio State University College of Public Health; and Monica E. Lindgren, Stephen P. Povoski, Adele M. Lipari, Doreen M. Agnese, William B. Farrar, Lisa D. Yee, William E. Carson III, and Janice K. Kiecolt-Glaser, The Ohio State University, Columbus, OH.
authors.forename: Janice K
authors.initials: JK
authors.lastname: Kiecolt-Glaser
mesh_terms: D019588:Aging, Premature / Q000209:etiology*; D001943:Breast Neoplasms / Q000097:blood / Q000150:complications / Q000401:mortality / Q000628:therapy*; D003131:Combined Modality Therapy; D015897:Comorbidity; D048749:Cytokinesis / Q000502:physiology; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008137:Longitudinal Studies; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha