Social well-being is associated with less pro-inflammatory and pro-metastatic leukocyte gene expression in women after surgery for breast cancer
- 413 Downloads
Satisfaction with social resources, or “social well-being,” relates to better adaptation and longer survival after breast cancer diagnosis. Biobehavioral mechanisms linking social well-being (SWB) to mental and physical health may involve inflammatory signaling. We tested whether reports of greater SWB were associated with lower levels of pro-inflammatory and pro-metastatic leukocyte gene expression after surgery for non-metastatic breast cancer.
Women (N = 50) diagnosed with non-metastatic (0–III) breast cancer were enrolled 2–8 weeks after surgery. SWB was assessed with the social/family well-being subscale of the FACT-B. Leukocyte gene expression for specific pro-inflammatory (cytokines, chemokines, and COX-2) and pro-metastatic genes (e.g., MMP9) was derived from microarray analysis.
Multiple regression analyses controlling for age, stage of disease, days since surgery, education, and body mass index (BMI) found higher levels of SWB related to less leukocyte pro-inflammatory and pro-metastatic gene expression (p < 0.05). Emotional well-being, physical well-being, and functional well-being did not relate to leukocyte gene expression (p > 0.05). Greater SWB remained significantly associated with less leukocyte pro-inflammatory and pro-metastatic gene expression after controlling for depressive symptoms.
Results have implications for understanding mechanisms linking social resources to health-relevant biological processes in breast cancer patients undergoing primary treatment.
Clinical Trial Registration Number: NCT01422551
KeywordsBreast cancer Social well-being Social support Inflammation Leukocyte gene expression
This study was funded by the National Cancer Institute of the National Institutes of Health [R01-CA-064710], and the Sylvester Comprehensive Cancer Center.
Compliance with ethical standards
The experiments comply with the current laws of the country in which they were performed.
Conflict of interest
The authors declare that they have no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 1.American Cancer Society (2013) Breast cancer facts & figures 2013–2014. American Cancer Society, AtlantaGoogle Scholar
- 4.Reynolds P, Boyd PT, Blacklow RS, Jackson JS, Greenberg RS, Austin DF, Chen VW, Edwards BK, the National Cancer Institute Black/White Cancer Survival Study Group (1994) The relationship between social ties and survival among black and white breast cancer patients. Cancer Epidemiol Biomark Prev 3(3):253–259Google Scholar
- 5.Kroenke CH, Quesenberry C, Kwan ML, Sweeney C, Castillo A, Caan BJ (2013) Social networks, social support, and burden in relationships, and mortality after breast cancer diagnosis in the life after breast cancer epidemiology (LACE) study. Breast Cancer Res Treat 137(1):261–271. doi: 10.1007/s10549-012-2253-8 CrossRefPubMedGoogle Scholar
- 11.Cohen EN, Gao H, Anfossi S, Mego M, Reddy NG, Debeb B, Giordano A, Tin S, Wu Qiong, Garza RJ, Cristofanilli M, Mani SA, Croix DA, Ueno NT, Woodward WA, Luthra R, Krishnamurthy S, Reuben JM (2015) Inflammation mediated metastasis: immune induced epithelial-to-mesenchymal transition in inflammatory breast cancer cells. PLoS ONE 10(7):e0132710. doi: 10.1371/journal.pone.0132710 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Miller GE, Chen E, Sze J, Marin T, Arevalo JM, Doll R, Ma R, Cole SW (2008) A functional genomic fingerprint of chronic stress in humans: blunted glucocorticoid and increased NF-kappaB signaling. Biol Psychiatry 64(4):266–272. doi: 10.1016/j.biopsych.2008.03.017 CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Hughes S, Jaremka LM, Alfano CM, Glaser R, Povoski SP, Lipari AM, Agnese DM, Farrar WB, Yee LD, Carson WE 3rd, Malarkey WB, Kiecolt-Glaser JK (2014) Social support predicts inflammation, pain, and depressive symptoms: longitudinal relationships among breast cancer survivors. Psychoneuroendocrinology 42:38–44. doi: 10.1016/j.psyneuen.2013.12.016 CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Bouchard LC, Antoni MH, Blomberg BB, Stagl JM, Gudenkauf LM, Jutagir DR, Diaz A, Lechner S, Glück S, Derhagopian RP, Carver CS (2016) Postsurgical depressive symptoms and proinflammatory cytokine elevations in women undergoing primary treatment for breast cancer. Psychosom Med 78(1):26–37. doi: 10.1097/PSY.0000000000000261 CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Antoni MH, Lutgendorf SK, Blomberg B, Carver CS, Lechner S, Diaz A, Stagl J, Arevalo JMG, Cole SW (2012) Cognitive-behavioral stress management reverses anxiety-related leukocyte transcriptional dynamics. Biol Psychiatry 71(4):366–372. doi: 10.1016/j.biopsych.2011.10.007 CrossRefPubMedGoogle Scholar
- 22.Musselman DL, Somerset WI, Guo Y, Manatunga AK, Porter M, Penna S, Lewison B, Goodkin R, Lawson K, Lawson D, Evans DL, Nemeroff BC (2006) A double-blind, multicenter, parallel-group study of paroxetine, desipramine, or placebo in breast cancer (stages I, II, III, and IV) with major depression. J Clin Psychiatry 67(2):288–296CrossRefPubMedGoogle Scholar
- 27.Kline RB (2015) Principles and practice of structural equation modeling, 4th edn. The Guilford Press, New YorkGoogle Scholar
- 28.O’Connor MF, Bower JE, Cho HJ, Creswell JD, Dimitrov S, Hamby ME, Hoyt MA, Martin JL, Robles TF, Sloan EK, Thomas KS, Irwin MR (2009) To assess, to control, to exclude: effects of biobehavioral factors on circulating inflammatory markers. Brain Behav Immun 23(7):887–897. doi: 10.1016/j.bbi.2009.04.005 CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol 57(1):289–300Google Scholar
- 30.Jansen R, Penninx BWJH, Madar V, Xia K, Milaneschi Y, Hottenga JJ, Hammerschlag AR, Beekman A, van der Wee N, Smit JH, Brooks A, Tischfield J, Posthuma D, Schoevers R, van Grootheest G, Willemsen G, de Geus EJ, Boomsma DI, Wright FA, Zou F, Sun W, Sullivan PF (2016) Gene expression in major depressive disorder. Mol Psychiatry 21(3):339–347. doi: 10.1038/mp.2015.94 CrossRefPubMedGoogle Scholar
- 31.U.S. Census Bureau. (2002). Florida: 2000. Retrieved January 1, 2017, from https://www.census.gov/prod/2002pubs/c2kprof00-fl.pdf
- 32.Bower JE, Ganz PA, Irwin MR, Arevalo JM, Cole SW (2011) Fatigue and gene expression in human leukocytes: increased NF-κB and decreased glucocorticoid signaling in breast cancer survivors with persistent fatigue. Brain Behav Immun 25(1):147–150. doi: 10.1016/j.bbi.2010.09.010 CrossRefPubMedGoogle Scholar
- 33.Fenlon D, Powers C, Simmonds P, Clough J, Addington-Hall J (2014) The JACS prospective cohort study of newly diagnosed women with breast cancer investigating joint and muscle pain, aches, and stiffness: pain and quality of life after primary surgery and before adjuvant treatment. BMC Cancer 14:467. doi: 10.1186/1471-2407-14-467 CrossRefPubMedPubMedCentralGoogle Scholar
- 37.Lee JW, Shahzad MM, Lin YG, Armaiz-Pena G, Mangala LS, Han HD, Kim HS, Nam EJ, Jennings NB, Halder J, Nick AM, Stone RL, Lu C, Lutgendorf SK, Cole SW, Lokshin AE, Sood AK (2009) Surgical stress promotes tumor growth in ovarian carcinoma. Clin Cancer Res 15(8):2695–2702. doi: 10.1158/1078-0432.CCR-08-2966 CrossRefPubMedPubMedCentralGoogle Scholar
- 39.Miller GE, Chen E, Fok AK, Walker H, Lim A, Nicholls EF, Cole S, Kobor MS (2009) Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling. Proc Natl Acad Sci 106(34):14716–14721. doi: 10.1073/pnas.0902971106 CrossRefPubMedPubMedCentralGoogle Scholar
- 40.Lutgendorf SK, Lamkin DM, Jennings NB, Arevalo JM, Penedo F, DeGeest K, Langley RR, Lucci JA 3rd, Cole SW, Lubaroff DM, Sood AK (2008) Biobehavioral influences on matrix metalloproteinase expression in ovarian carcinoma. Clin Cancer Res 14(21):6839–6846. doi: 10.1158/1078-0432.CCR-08-0230 CrossRefPubMedPubMedCentralGoogle Scholar
- 42.Le CP, Nowell CJ, Kim-Fuchs C, Botteri E, Hiller JG, Ismail H, Pimentel MA, Chai MG, Karnezis T, Rotmensz N, Renne G, Gandini S, Pouton CW, Ferrari D, Möller A, Stacker SA, Sloan EK (2016) Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination. Nat Commun 1(7):10634. doi: 10.1038/ncomms10634 CrossRefGoogle Scholar
- 46.Jutagir DR, Gudenkauf LM, Stagl JM, Carver CS, Bouchard LC, Lechner SC, Glück S, Blomberg BB, Antoni MH (2015) Ethnic differences in types of social support from multiple sources after breast cancer surgery. Ethn Health 21(5):411–425. doi: 10.1080/13557858.2015.1066494 CrossRefPubMedPubMedCentralGoogle Scholar
- 47.Pruitt KD, Brown GR, Hiatt SM, Thibaud-Nissen F, Astashyn A, Ermolaeva O, Farrell CM, Hart J, Landrum MJ, McGarvey KM, Murphy MR, O’Leary NA, Pujar S, Rajput B, Rangwala SH, Riddick LD, Shkeda A, Sun H, Tamez P, Tully RE, Wallin C, Webb D, Weber J, Wu W, DiCuccio M, Kitts P, Maglott DR, Murphy TD, Ostell JM (2014) RefSeq: an update on mammalian reference sequences. Nucl Acids Res 42 (Database issue):D756–D763. doi: 10.1093/nar/gkt1114 CrossRefGoogle Scholar