Inflammatory Cytokine Levels and Breast Cancer Risk Factors: Racial Differences of Healthy Caucasian and African American Women

Na-Jin Park

Duck-Hee Kang

cytokines, breast cancer, risk factors, African American
ONF 2013, 40(5), 490-500. DOI: 10.1188/13.ONF.40-05AP

Purpose/Objectives: To examine racial differences in inflammatory cytokine levels (interleukin [IL]-6 and interferon-gamma [IFN-γ]) and breast cancer (BC) risk factors between healthy Caucasian and African American women; to examine differences in relationships of inflammatory cytokine levels with BC risk factors between these groups of women; and to determine the independent contribution of race to IL-6 and IFN-γ after controlling for relevant covariates.

Design: Cross-sectional and correlational descriptive design.

Setting: Community surrounding a state university health system in the southeastern United States.

Sample: 113 healthy women (65 Caucasians and 48 African Americans) aged 20 years or older and not pregnant.

Methods: Secondary analysis of data collected from self-report questionnaires and blood samples.

Main Research Variables: Inflammatory cytokine levels, BC risk factors (age, age at menarche, age at first live birth, family history of BC, breast biopsy, breastfeeding history and duration, body mass index, and physical activity), and race.

Findings: Significant racial differences were noted in IL-6 and IFN-γ levels, reproductive or hormonal and lifestyle BC risk factors, and relationships between African American and Caucasian women. Controlling for all other effects, race appeared to be a significant predictor for IL-6 and IFN-γ.

Conclusions: Racial differences in inflammatory cytokines and BC risk factors may provide partial evidence for existing racial disparities in BC for African American and Caucasian women. Additional studies are needed to confirm that potential.

Implications for Nursing: Additional biobehavioral research in racial disparities in BC may help to inform nurses to target race-specific modifications of lifestyle and behavioral factors to reduce BC health disparity between African American and Caucasian women.

Knowledge Translation: Being an African American woman predicted a higher level of inflammatory cytokine production after controlling for selected BC risk factors. Great potential exists for inflammatory responses as one of the underlying biologic mechanisms for existing BC disparity and for culturally tailored lifestyle or behavioral modification interventions for reducing BC risk and racial disparity.

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    Albain, K. S., Unger, J. M., Crowley, J. J., Coltman, C. A. J., & Hershman, D. L. (2009). Racial disparities in cancer survival among randomized clinical trials patients of the Southwest Oncology Group. Journal of the National Cancer Institute, 101, 984-992. doi:10.1093/jnci/djp175
    Amend, K., Hicks, D., & Ambrosone, C. B. (2006). Breast cancer in African American women: Differences in tumor biolgoy from European American women. Cancer Research, 66, 8327-8330.
    American Cancer Society. (2011). Breast cancer facts and figures 2011-2012. Atlanta, GA: Author.
    Berger, F. G. (2004). The interleukin-6 gene: A susceptibility factor that may contribute to racial and ethnic disparities in breast cancer mortality. Breast Cancer Research and Treatment, 88, 281-285.
    Bernstein, L., Teal, C. R., Joslyn, S., & Wilson, J. (2003). Ethnicity-related variation in breast cancer risk factors. Cancer, 97(1, Suppl.), 222-229.
    Carroll, J. F., Fulda, K. G., Chiapa, A. L., Rodriquez, M., Phelps, D. R., Cardarelli, K. M., … Cardarelli, R. (2009). Impact of race/ethnicity on the relationship between viscerall fat and inflammatory biomarkers. Obesity, 17, 1420-1427.
    Clemons, M., & Goss, P. (2001). Estrogen and the mechanism of breast cancer. New England Journal of Medicine, 344, 276-285.
    Cohen, J. (1988). Statistical power analysis for the behavioral sciences (2nd ed.). Hillsdale, NJ: Erlbaum.
    Cole, S. W. (2009). Chronic inflammation and breast cancer recurrence. Journal of Clinical Oncology, 27, 3418-3419. doi:10.1200/JCO.2009.21.9782
    Collaborative Group on Hormonal Factors in Breast Cancer. (2002). Breast cancer and breastfeeding: Collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50,302 women with breast cancer and 96,973 women without the disease. Lancet, 20, 187-195.
    Ershler, W. B., & Keller, E. T. (2000). Age-associated increased interleukin-6 gene expression, late-life diseases, and fraility. Annual Review of Medicine, 51, 245-270.
    Forshee, R. A., Storey, M. L., & Ritenbaugh, C. (2003). Breast cancer risk and lifestyle differences among premenopausal and postmenopausal African American women and White women. Cancer, 97(1, Suppl.), 280-288.
    Friedenreich, C. M., & Orenstein, M. R. (2002). Physical activity and cancer prevention: Etiologic evidence and biological mechanisms. Journal of Nutrition, 132(Suppl.), 3456S-3464S.
    Friedman, E. M., & Herd, P. (2010). Income, education, and inflammation: Differential associations in a national probability sample (the MIDUS Study). Psychosomatic Medicine, 72, 290-300. doi:10.1097/PSY.0b013e3181cfe4c2
    Gail, M. H., Brinton, L. A., Byar, D. P., Corle, D. K., Green, S. B., Schairer, C., & Mulvihill, J. J. (1989). Projecting individualized probabilities of developing breast cancer for White females who are being examined annually. Journal of the National Cancer Institute, 81, 1879-1886.
    Gerend, M. A., & Pai, M. (2008). Social determinants of Black-White disparities in breast cancer mortality: A review. Cancer Epidemiology, Biomarkers and Prevention, 17, 2913-2923. doi:10.1158/1055-9965.EPI-07-0633
    Goswami, B., Rajappa, M., Sharma, M., & Sharma, A. (2008). Inflammation: Its role and interplay in the development of cancer, with special focus on gynecological malignancies. International Journal of Gynecological Cancer, 18, 591-599.
    Govan, V. A., Carrara, H. R. O., Sachs, J. A., Hoffman, M., Stanczuk, G. A., & Williamson, A. L. (2003). Ethnic differences in allelic distribution of IFN-γ in South African women but no link with cervical cancer. Journal of Carcinogenesis, 2, 3. doi:10.1186/1477-3163-2-3
    Groer, M. W., Davis, M. W., & Hemphill, J. (2002). Postpartum stress: Current concepts and the possible protective role of breastfeeding. Journal of Obstetric, Gynecologic, and Neonatal Nursing, 31, 411-417.
    Hall, I. J., Moorman, P. G., Millikan, R. C., & Newman, B. (2005). Comparative analysis of breast cancer risk factors among African American women and White women. American Journal of Epidemiology, 161, 40-51.
    Hamer, M., & Steptoe, A. (2009). Prospective study of physical fitness, adiposity, and inflammatory markers in healthy middle-aged men and women. American Journal of Clinical Nutrition, 89, 85-89. doi:10.3945/ajcn.2008.26779
    Hassan, M. I., Aschner, Y., Manning, C. H., Xu, J., & Aschner, J. L. (2003). Racial differences in selected cytokine allelic and genotypic frequencise among healthy, pregnant women in North Carolina. Cytokine, 21, 10-16.
    Horowitz, M., Wilner, N., & Alvarez, W. (1979). Impact of Event Scale: A measure of subjective stress. Psychosomatic Medicine, 41, 209-218.
    Howren, M. B., Lamkin, D. M., & Suls, J. (2009). Associations of depression with C-reactive protein, IL-1, and IL-6: A meta-analysis. Psychosomatic Medicine, 71, 171-186.
    Il'yasova, D., Colbert, L. H., Harris, T. B., Newman, A. B., Bauer, D. C., Satterfield, S., & Kritchevsky, S. B. (2005). Circulating levels of inflammatory markers and cancer risk in the Health Aging and Body Composition Cohort. Cancer Epidemiology, Biomarkers and Prevention, 14, 2413-2418.
    Ip, S., Chung, M., Raman, G., Trikalinos, T. A., & Lau, J. (2009). A summary of the Agency for Healthcare Research and Quality's evidence report on breastfeeding in developed countires. Breastfeeding Medicine, 4(Suppl. 1), S17-S30. doi:10.1089/bfm.2009.0050
    Jabbour, H. N., Sales, K. J., Catalano, R. D., & Norman, J. E. (2009). Inflammatory pathways in female reproductive health and disease. Reproduction, 138, 903-919.
    John, E. M., Horn-Ross, P. L., & Koo, J. (2003). Lifetime physical activity and breast cancer risk in a multiethnic population: The San Francisco Bay Area Breast Cancer Study. Cancer Epidemiology, Biomarkers and Prevention, 12, 1143-1152.
    Joslyn, S. A., & West, M. M. (2000). Racial differences in breast carcinoma survival. Cancer, 88, 114-123.
    Kang, D. H., McArdle, T., Park, N. J., Weaver, M. T., Smith, B., & Carpenter, J. (2011). Dose effects of relaxation practice on immune responses in women newly diagnosed with breast cancer: An explorary study [Online exclusive]. Oncology Nursing Forum, 38, E240-E252. doi:10.1188/11.ONF.E240-E252
    Kang, D. H., Rice, M., Park, N. J., Turner-Henson, A., & Downs, C. (2010). Stress and inflammation: A biobehavioral approach for nursing research. Western Journal of Nursing Research, 32, 730-760.
    Kasapis, C., & Thompson, P. D. (2005). The effects of physical activity on serum C-reactive protein and inflammatory markers: A systematic review. Journal of the American College of Cardiology, 45, 1563-1569.
    Kiecolt-Glaser, J. K., Preacher, K. J., MacCallum, R. C., Atkinson, C., & Malarkey, W. B. (2003). Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proceedings of the National Academy of Sciences, 100, 9090-9095.
    Lahmann, P. H., Hoffmann, K., Allen, N., van Gils, C. H., Khaw, K. T., Tehard, B., … Elio, R. (2004). Body size and breast cancer risk: Findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). International Journal of Cancer, 111, 762-771.
    Liu, Q., Wuu, J., Lambe, M., Hsiech, S. F., Ekbom, A., & Hsieh, C. C. (2002). Transient increase in breast cancer risk after giving birth: Postpartum period with the highest risk (Sweden). Cancer Causes and Control, 13, 299-305.
    McCullough, M. L., Feigelson, H. S., Diver, W. R., Patel, A. V., Thun, M. J., & Calle, E. E. (2005). Risk factors for fatal breast cancer in African American women and White women in a large U. S. prospective cohort. American Journal of Epidemiology, 162, 734-742.
    Millikan, R. C., Newman, B., Tse, C. K., Moorman, P. G., Conway, K., Dressler, L. G., … Perou, C. M. (2008). Epidemiology of basal-like breast cancer. Breast Cancer Research and Treatment, 109, 123-139.
    Mohamed-Ali, V., Goodrick, S., Katz, R. D. R., Miles, J. M., Yudkin, J. S., Klein, S., & Coppack, S. W. (1997). Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. Journal of Clinical Endocrinology and Metabolism, 82, 4196-4200.
    Ness, R. B., Haggerty, C. L., Harger, G., & Ferrell, R. (2004). Differential distribution of allelic variants in cytokine genes among African Americans and White Americans. American Journal of Epidemiology, 160, 1033-1038. doi:10.1093/aje/kwh325
    Palmer, J. R., Wise, L. A., Horton, N. J., Adams-Campbell, L. L., & Rosenberg, L. (2003). Dual effect of parity on breast cancer risk in African American women. Journal of the National Cancer Institute, 95, 478-483.
    Park, N. J., Kang, D. H., & Weaver, M. T. (2010). Objective and subjective breast cancer risk: Relationships with natural killer cell activity and psychological distress in healthy women. Cancer Nursing, 33, 411-420. doi:10.1097/NCC.0b013e3181dc37a1
    Phipps, A. I., Chlebowski, R. T., McTiernan, A., Stefanick, M. L., Wactawski-Wende, J., Kuller, L. H., … Li, C. I. (2011). Body size, physical activity, and risk of triple-negative and estrogen receptor-positive breast cancer. Cancer Epidemiology, Biomarkers and Prevention, 20, 454-463. doi:10.1158/1055-9965.EPI-10-0974
    Pierce, B. L., Ballard-Barbash, R., Bernstein, L., Baumgartner, R. N., Neuhouser, M. L., Wener, M. H., … Ulrich, C. M. (2009). Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients. Journal of Clinical Oncology, 27, 3437-3444. doi:10.1200/JCO.2008.18.9068
    Pike, M. C., Spicer, D. V., Dahmoush, L., & Press, M. F. (1993). Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiologic Reviews, 15, 17-35.
    Rao, K. M., Pieper, C. S., Currie, M. S., & Cohen, H. J. (1994). Variability of plasma IL-6 and crosslinked fibrin dimers over time in community dwelling elderly subjects. American Journal of Clinical Pathology, 102, 802-805.
    Rockhill, B., Spiegelman, D., Byrne, C., Hunter, D. J., & Colditz, G. A. (2001). Validation of the Gail model of breast cancer risk prediction and implications for chemoprevention. Journal of the National Cancer Institute, 93, 358-366. doi:10.1093/jnci/93.5.358
    Russo, J., Tay, L. K., & Russo, I. H. (1982). Differentiation of the mammary gland and susceptibility to carcinogenesis. Breast Cancer Research and Treatment, 2, 5-73. doi:10.1007/BF01805718
    Shavers, V. L., Harlan, L. C., & Stevens, J. L. (2003). Racial/ethnic variation in clinical presentation, treatment, and survival among breast cancer patients under age 35. Cancer, 97, 134-147. doi:10.1002/cncr.11051
    Stead, L. A., Lash, T. L., Sobieraj, J. E., Chi, D. D., Westrup, J. L., Charlot, M., … Rosenberg, C. L. (2009). Triple-negative breast cancers are increased in Black women regardless of age or body mass index. Breast Cancer Research, 11, R18. doi:10.1186/bcr2242
    Stowe, R. P., Peek, M. K., Cutchin, M. P., & Goodwin, J. S. (2010). Plasma cytokine levels in a population-based study: Relation to age and ethnicity. Journal of Gerontology: Medical Sciences, 65A, 429-433. doi:10.1093/gerona/glp198
    Tice, J. A., Cummings, S. R., Smith-Bindman, R., Ichikawa, L., Barlow, W. E., & Kerlikowske, K. (2008). Using clinical factors and mammographic breast density to estimate breast cancer risk: Development and validation of a new predictive model. Annals of Internal Medicine, 148, 337-347. doi:10.7326/0003-4819-148-5-200803040-00004
    Ursin, G., Longnecker, M., & Haile, R. (1995). A meta-analysis of body mass index and risk of premenopausal breast cancer. Epidemiology, 6, 137-141. doi:10.1097/00001648-199503000-00009
    Wee, C. C., Mukamal, K. J., Huang, A., Davis, R. B., McCarthy, E. P., & Mittleman, M. A. (2008). Obesity and C-reactive protein levels among White, Black, and Hispanic U. S. adults. Obesity, 16, 875-880. doi:10.1038/oby.2008.7
    Zabaleta, J., Schneider, B. G., Ryckman, K., Hooper, P. F., Camargo, M. C., Piazuelo, M. B., … Ochoa, A. C. (2008). Ethnic differences in cytokine gene polymorphisms: Potential implications for cancer development. Cancer Immunology and Immunotherapy, 57, 107-114. doi:10.1007/s00262-007-0358-4