Article
Association Between Serotonin Transport Polymorphisms and Postdischarge Nausea and Vomiting in Women Following Breast Cancer Surgery
Purpose/Objectives: To examine the association of the serotonin transport gene and postdischarge nausea and vomiting (PDNV) in women following breast cancer surgery.
Design: A cross-sectional study.
Setting: A comprehensive cancer center in Pittsburgh, PA.
Sample: 80 post-menopausal women treated surgically for early-stage breast cancer.
Methods: Data were collected using standardized instruments after surgery but before the initiation of chemotherapy. Blood or saliva were used for DNA extraction and analyzed following standardized protocols. Data were analyzed using descriptive statistics and logistic regression.
Main Research Variables: Serotonin transport gene (SLC6A4), nausea, vomiting, pain, and anxiety.
Findings: Women who inherited the LA/LA genotypes were at greater risk for nausea and vomiting when compared to women who carried any other combination of genotypes. Twenty-one percent of women reported nausea and vomiting an average of one month following surgery and prior to initiation of adjuvant therapy. Those women who experienced PDNV reported significantly higher anxiety and pain scores.
Conclusions: Findings of this study suggest that variability in the genotypes of the serotonin transport gene may help to explain the variability in PDNV in women following breast cancer surgery and why 20%-30% of patients do not respond to antiemetic medications.
Implications for Nursing: Nurses need to be aware that women who do not experience postoperative nausea and vomiting following surgery for breast cancer continue to be at risk for PDNV long after they have been discharged from the hospital, and this frequently is accompanied by pain and anxiety.
Jump to a section
References
Alfano, C.M., McGregor, B.A., Kuniyuki, A., Reeve, B.B., Bowen, D.J., Baumgartner, K.B., … McTiernan, A. (2006). Psychometric properties of a tool for measuring hormone-related symptoms in breast cancer survivors. Psycho-Oncology, 15, 985-1000.
Apfel, C.C., Heidrich, F.M., Jukar-Rao, S., Jalota, L., Hornuss, C., Whelan, R.P., … Cakmakkaya, O.S. (2012). Evidence-based analysis of risk factors for postoperative nausea and vomiting. British Journal of Anaesthesia, 109, 742-753. doi:10.1093/bja/aes276
Apfel, C.C., Korttila, K., Abdalla, M., Kerger, H., Turan, A., Vedder, I., … Roewer, N. (2004). A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. New England Journal of Medicine, 350, 2441-2451.
Apfel, C.C., Kranke, P., & Eberhart, L.H. (2004). Comparison of surgical site and patient's history with a simplified risk score for the prediction of postoperative nausea and vomiting. Anaesthesia, 59, 1078-1082.
Apfel, C.C., Philip, B.K., Cakmakkaya, O.S., Shilling, A., Shi, Y.Y., Leslie, J.B., … Kovac, A. (2012). Who is at risk for postdischarge nausea and vomiting after ambulatory surgery? Anesthesiology, 117, 475-486.
Basch, E., Prestrud, AA., Hesketh, P.J., Kris, M.G., Feyer, P.C., Somerfield, M.R., … Lyman, G.H. (2011). Antiemetics: American Society of Clinical Oncology clinical practice guideline update. Journal of Clinical Oncology, 29, 4189-4198. doi:10.1200/JCO.2010.34.4614
Chia, Y.Y., Kuo, M.C., Liu, K., Sun, G.C., Hsieh, S.W., & Chow, L.H. (2002). Does postoperative pain induce emesis? Clinical Journal of Pain, 18, 317-323.
Cleeland, C.S. (2006). The measurement of pain from metastatic bone disease: Capturing the patient's experience. Clinical Cancer Research, 12 (Part 2), 6236s-6242s. doi:10.1158/1078-0432.CCR-06-0988
Cleeland, C.S., Ladinsky, J.L., Serlin, R.C., & Nugyen, C.T. (1988). Multidemensional measurement of the cancer pain: Comparisons of U.S. and Vietnamese patients. Journal of Pain and Symptom Management, 3, 23-27.
Cohen, L., de Moor, C.A., Eisenberg, P., Ming, E.E., & Hu, H. (2007). Chemotherapy-induced nausea and vomiting: Incidence and impact on patient quality of life at community oncology settings. Supportive Care in Cancer, 15, 497-503.
Cruthirds, D., Sims, P.J., & Louis, P.J. (2013). Review and recommendations for the prevention, management, and treatment of postoperative and postdischarge nausea and vomiting. Oral Surgery, Oral Medicine, Oral Pathology, and Oral Radiology, 115, 601-611.
Gan, T.J. (2006). Risk factors for postoperative nausea and vomiting. Anesthesia and Analgesia, 102, 1884-1898.
Gan, T.J., Meyer, T.A., Apfel, C.C., Chung, F., Davis, P.J., Habib, A.S., … Watcha, M. (2007). Society for Ambulatory Anesthesia guidelines for the management of postoperative nausea and vomiting. Anesthesia and Analgesia, 105, 1615-1628.
Gupta, M., Davis, M., Legrand, S., Walsh, D., & Lagman, R. (2013). Nausea and vomiting in advanced cancer: The Cleveland Clinic protocol. Journal of Support Oncology, 11, 8-13. doi:10.1016/j.suponc.2012.10.002
Hu, X., Lipsky, R., Zhu, G., Akhtar, L., Taubman, J., Greenberg, B., … Goldman, D. (2006). Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. American Journal of Human Genetics, 78, 815-826. doi:10.1086/503850
Jolley, S. (2001). Managing post-operative nausea and vomiting. Nursing Standards, 15, 47-52.
Kaiser, R., Tremblay, P.B., Sezer, O., Possinger, K., Roots, I., & Brockmöller, J. (2004). Investigation of the association between 5-HT3A receptor gene polymorphisms and efficiency of antiemetic treatment with 5-HT3 receptor antagonists. Pharmacogenetics, 14, 271-278.
Kapstad, H., Rokne, B., & Stavem, K. (2010). Psychometric properties of the Brief Pain Inventory among patients with osteoarthritis undergoing total hip replacement surgery. Health and Quality of Life Outcomes, 8, 148. doi:10.1186/1477-7525-8-148
Kerger, H., Turan, A., Kredel, M., Stuckert, U., Alsip, N., Gan, T.J., & Apfel, C.C. (2007). Patients' willingness to pay for antiemetic treatment. Acta Anaesthesiologica Scandinvica, 51, 38-43.
Kosek, E., Jensen, K., Lonsdorf, T., Schalling, M., & Ingvar, M. (2009). Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid remifentanil in humans. Molecular Pain, 5(37), 1-7. doi:10.1186/1744-8069-5-37
Laugsand, E.A., Fladvad, T., Skorpen, F., Maltoni, M., Kaasa, S., Fayers, P., & Klepstad, P. (2011). Clinical and genetic factors associated with nausea and vomiting in cancer patients receiving opioids. European Journal of Cancer, 47, 1682-1691. doi:10.1016/j.ejca.2011.04.014
Lee, H.J., Kwon, J.Y., Shin, S.W., Kim, C.H., Baek, S.H., Baik, S.W., … Kim, K.H, (2008). Preoperatively administered ramosetron oral disintegrating tablets for preventing nausea and vomiting associated with patient-controlled analgesia in breast cancer patients. European Journal of Anaesthesiology, 25, 756-762. doi:10.1017/S0265021508004262
Lerman, C., & Schwartz, M. (1993). Adherence and psychological adjustment among women at high risk for breast cancer. Breast Cancer Research and Treatment, 28, 145-155.
Levangie, P., & Drouin, J. (2009). Magnitude of late effects of breast cancer treatments on shoulder function: A systematic review. Breast Cancer Research and Treatment, 116, 1-15. doi:10.1007/s10549-008-0246-4
Macario, A., Weinger, M., Carney, S., & Kim, A. (1999). Which clinical anesthesia outcomes are important to avoid? The perspective of patients. Anaesthesia and Analgesia, 89, 652-658.
Marla, S., & Stallard, S. (2009). Systematic review of day surgery for breast cancer. International Journal of Surgery, 7, 318-323. doi:10.1016/j.ijsu.2009.04.015
McNair, D.M., Lorr, M., & Droppleman, L.F. (1992). EdITS manual for the Profile of Mood States. San Diego, CA: Educational and Industrial Testing Service.
Melton, M.S., Klein, S.M., & Gan, T.J. (2011). Management of postdischarge nausea and vomiting after ambulatory surgery. Current Opinion in Anestehsiology, 24, 612-619. doi:10.1097/ACO.0b013e32834b9468
Miaskowski, C. (2009). A review of the incidence, causes, consequences, and management of gastrointerstinal effects associated with postoperative opioid administration. Journal of Perianesthesia Nursing, 24, 222-228. doi:10.1016/j.jopan.2009.05.095
Montgomery, G.H., Schnur, J.B., Erblich, J., Diefenbach, M.A., & Bovbjerg, D.H. (2010). Presurgery psychological factors predict pain, nausea, and fatigue one week after breast cancer surgery. Journal of Pain and Symptom Management, 39, 1043-1052. doi:10.1016/j.jpainsymman.2009.11.318
Murphy, D., & Moya, P. (2011). Human serotonin transporter gene (SLC6A4) variants: Their contributions to understanding pharmacogenomic and other functional GxG and GxE differences in health and disease. Current Opinion in Pharmacology, 11, 3-10. doi:10.1016/j.coph.2011.02.008
Pirri, C., Bayliss, E., Trotter, J., Olver, I.N., Katris, P., Drummond, P., & Bennett, R. (2013). Nausea still the poor relation in antiemetic therapy? The impact on cancer patients' quality of life and psychological adjustment of nausea, vomiting, and appetite loss, individually and concurrently as part of a symptom cluster. Supportive Care in Cancer, 21, 735-748. doi:10.1007/s00520-012-1574-9
Poleshuck, E.L., Katz, J., Andrus, C.H., Hogan, L.A., Jung, B.F., Kulick, D.I., & Dworkin, R.H. (2006). Risk factors for chronic pain following breast cancer surgery: A prospective study. Journal of Pain, 7, 626-634.
Rueffert, H., Thieme, V., Wallenborn, J., Lemnitz, N., Bergmann, A., Rudolf, K., … Kaisers, U.X. (2009). Do variations in the 5-HT3A and 5-HT3B serotonin receptor genes (HTR3A and HTR3B) influence the occurrence of postoperative vomiting? Anesthesiology and Analgesia, 109, 1442-1447. doi:10.1213/ane.0b013e3181b2359b
Singhal, A.K., Kannan, S., & Gota, V.S. (2012). 5HT3 antagonists for prophyslaxis of postoperative nausea and vomiting in breast surgery: A meta-analysis. Journal of Postgraduate Medicine, 58, 22-31.
Stanton, A.L., Bernaards, C.A., & Ganz, P.A. (2005). The BCPT symptom scales: A measure of physical symptoms for women diagnosed with or at risk for breast cancer. Journal of the National Cancer Institute, 97, 448-456. doi:10.1093/jnci/dji069
Stewart, M.W. (2013). Research news: Postdischarge nausea and vomiting. Journal of Perianesthesia Nursing, 28, 40-42. doi:10.1016/j.jopan.2012.11.003.
Sweeney, B.P. (2002). Why does smoking protect against PONV. British Journal of Anaesthesia, 89, 810-813.
Terhorst, L., Blair-Belansky, H., Moore, P.J., & Bender, C. (2011). Evaluation of the psychometric properties of the BCPT Symptom Checklist with a sample of breast cancer patients before and after adjuvant therapy. Psycho-Oncology, 20, 961-968. doi:10.1002/pon.1806
Tofthagen, C. (2010). Patient perceptions associated with chemotherapy-induced peripheral neuropathy [Online exclusive]. Clinical Journal of Oncology Nursing, 14, E22-E28. doi:10.1188/10.CJON.E22-E28
Treister, R., Pud, D., Ebstein, R.P., Laiba, E., Raz, Y., Gershon, E., … Eisenberg, E. (2011). Association between polymorphisms in serotonin and dopamine-related genes and endogenous pain modulation. Journal of Pain, 12, 875-883. doi:10.1016/j.jpain.2011.02.348
Tremblay, P.B., Kaiser, R., Sezer, O., Rosler, N., Schelenz, C., Possinger, K., … Brockmoller, J. (2003). Variations in the 5-hydroxytryptamine type 3B receptor gene as predictors of the efficicacy of antiemetic treatment in cancer patients. Journal of Clinical Oncology, 21, 2147-2155.
Watcha, M.F., & White, P.F. (1992). Postoperative nausea and vomiting. Its etiology, treatment, and prevention. Anesthesiology, 77, 162-184.
Wendland, J.R., Martin, B.J., Kruse, M.R., Lesch, K.P., & Murphy, D.L. (2006). Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531. Molecular Psychiatry, 11, 224-226.
Wesmiller, S.W., Henker, R.A., Sereika, S.M., Donovan, H.S., Meng, L., Gruen, G.S., … Conley, Y.P. (2012). The association of CYP2D6 genotype and postoperative nausea and vomiting in orthopedic trauma patients. Biological Research for Nursing, 15, 382-389. doi:10.1177/1099800412449181
Wickham, R. (2004). Nausea and vomiting. In C. Yarbro, M. Frogge, & M. Goodman (Eds.), Cancer symptom management (pp. 187-210). Sudbury, MA: Jones and Bartlett Learning.