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Supportive Care in Cancer

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01-02-2019 | Original Article

Examining the effect of 5-HTTLPR on depressive symptoms in postmenopausal women 1 year after initial breast cancer treatment

Authors: Justine S. Wang, Yvette P. Conley, Susan M. Sereika, Catherine M. Bender, Poorwa Godbole, Susan W. Wesmiller

Published in: Supportive Care in Cancer | Issue 2/2019

Abstract

Background

Depression following the diagnosis of breast cancer has been well documented, and occurs in as many as 40% of women. The serotonin transporter gene SLC6A4 and its functional polymorphism 5-HTTLPR have been extensively studied as factors in the development of depression. Many research studies have demonstrated conflicting results, and the contribution of 5-HTTLPR to depression is unclear.

Purpose

The purpose of this study was to compare the relationship between depressive symptoms and serotonin transporter gene polymorphisms between women with early-stage breast cancer 1 year following initial diagnosis and surgery and matched controls.

Methods

Participants (N = 125), included postmenopausal women following breast cancer surgery (n = 80) and age-and education-matched healthy controls (n = 45). The genetic elements of interest were the long (LA) and short (S) alleles of 5-HTTLPR, as well as the single nucleotide polymorphism rs25531 A > G within the L-allele (LG). DNA was extracted from either blood or saliva and analyzed for the SLC6A4 polymorphisms. The outcome measures for this longitudinal study included Beck Depression Inventory scores and physical function domain scores from the Medical Outcome Study Short Form 36. Results: Women with breast cancer demonstrated greater depressive symptomatology and decreased physical function compared to healthy controls. The LA/LA genotype was associated with increased depressive symptomatology in the overall sample and within the controls. The LA/LA genotype appeared with greater frequency in the experimental group, but the relationship with increased depressive symptoms was not observed. Physical function was a significant (p < 0.00) predictor of depressive symptoms in both groups at 12 months.

Conclusion

The relationship between 5-HTTLPR and depressive symptomatology in breast cancer patients remains unclear. A potential clinical application includes monitoring physical function and addressing increased depressive symptoms as physical function declines.

American Cancer Society, (2017). Breast Cancer Facts and Figures 2017.1/31/2017; Available from: http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-key-statistics

Stafford L, Judd F, Gibson P, Komiti A, Mann GB, Quinn M (2015) Anxiety and depression symptoms in the 2 years following diagnosis of breast or gynaecologic cancer: prevalence, course and determinants of outcome. Support Care Cancer 23(8):2215–2224PubMedCrossRef

Wong-Kim EC, Bloom JR (2005) Depression experienced by young women newly diagnosed with breast cancer. Psychooncology 14(7):564–573PubMedCrossRef

Stafford L, Judd F, Gibson P, Komiti A, Mann GB, Quinn M (2013) Screening for depression and anxiety in women with breast and gynaecologic cancer: course and prevalence of morbidity over 12 months. Psychooncology 22(9):2071–2078PubMedCrossRef

Burgess C, Cornelius V, Love S, Graham J, Richards M, Ramirez A (2005) Depression and anxiety in women with early breast cancer: five year observational cohort study. BMJ 330(7493):702PubMedPubMedCentralCrossRef

Wickham R (2004) Cancer symptom-management. Jones and Bartlett Learning, Burlington

So W, Marsh G, Ling W, Leung F, Lo J, Yeung M, Li G (2009) The symptom cluster of fatigue, pain, anxiety and depression and the effect on the quality of life of women receiving treatment for breast cancer. Oncol Nurs Forum 36(4):205–214CrossRef

Gonda X, Eszlari N, Kovacs D, Anderson IM, Deakin JF, Juhasz G, Bagdy G (2016) Financial difficulties but not other types of recent negative life events show strong interactions with 5-HTTLPR genotype in the development of depressive symptoms. Transl Psychiatry 6:e798. https://doi.org/10.1038/tp.2016.57 PubMedPubMedCentralCrossRef

Young SN, Leyton M (2002) The role of serotonin in human mood and social interaction. Insight from altered tryptophan levels. Pharmacol Biochem Behav 71(4):857–865PubMedCrossRef

10.

Schillani G, Martinis E, Capozzo MA, Era D, Cristante T, Mustacchi G, Conte MA, de Vanna M, Grassi L, Giraldi T (2010) Psychological response to cancer: role of 5-HTTLPR genetic polymorphism of serotonin transporter. Anticancer Res 30(9):3823–3826PubMed

11.

Weitzner MA, Meyers CA, Stuebing KK, Saleeba AK (1997) Relationship between quality of life and mood in long-term survivors of breast cancer treated with mastectomy. Support Care Cancer 5(3):241–248PubMedCrossRef

12.

Jones SM et al (2015) Depression and quality of life before and after breast cancer diagnosis in older women from the Women’s Health Initiative. J Cancer Surviv 9(4):620–629PubMedPubMedCentralCrossRef

13.

Mandorfer M, Payer BA, Scheiner B, Breitenecker F, Aichelburg MC, Grabmeier-Pfistershammer K, Rieger A, Trauner M, Peck-Radosavljevic M, Reiberger T (2014) Health-related quality of life and severity of fatigue in HIV/HCV co-infected patients before, during, and after antiviral therapy with pegylated interferon plus ribavirin. Liver Int 34(1):69–77PubMedCrossRef

14.

Banovic I, Gilibert D, Cosnes J (2010) Crohn’s disease and fatigue: constancy and co-variations of activity of the disease, depression, anxiety and subjective quality of life. BMC Psychol 15(4):394–405

15.

Dalgas U, Stenager E, Jakobsen J, Petersen T, Hansen HJ, Knudsen C, Overgaard K, Ingemann-Hansen T (2010) Fatigue, mood and quality of life improve in MS patients after progressive resistance training. Mult Scler 16(4):480–490PubMedCrossRef

16.

Reich M, Lesur A, Perdrizet-Chevallier C (2008) Depression, quality of life and breast cancer: a review. Breast Cancer Res Treat 110:9–17PubMedCrossRef

17.

Andritsch E, Dietmaier G, Hoffman G, Aloklikovots S, Samonigg H (2007) Global quality of life and its potential predictors in breast cancer patients: an exploratory study. Support Care Cancer 15(1):21–30PubMedCrossRef

18.

Mols F, Vingerhoets AJ, Coebergh JW, van de Poll-Franse LV (2005) Quality of life among long-term breast cancer survivors: a systematic review. Eur J Cancer 41:2613–2619PubMedCrossRef

19.

Weitzner MA, Meyers CA, Stuebing KK, Saleeba AK (1997) Relationship between quality of life and mood in long-term survivors of breast cancer with mastectomy. Support Care Cancer 5:241–248PubMedCrossRef

20.

Kim JM, Jang JE, Stewart R, Kim SY, Kim SW, Kang HJ, Shin S, Park MH, Yoon JH, Yoon JS (2013) Determinants of suicidal ideation in patients with breast cancer. Psycho-Oncology 22:2848–2856. https://doi.org/10.1002/pon.3367 PubMedCrossRef

21.

Bender C, Merriman J, Gentry A, Ahrendt G, Berga S, Brufsky A, Casillo F, Dailey M, Erickson K, Kratofil F, McAuliffe P, Ryan C, Sereika S (2015) Patterns of change in cognitive function with Anastrozole therapy. Cancer 121(15):2627–2636PubMedCrossRef

22.

Gardini A, Pisoni C, Giorgi I, Borelli V, Scoccia E, Majani G (2013) ICF, quality of life, and depression in breast cancer: perceived disability in disease-free women 6 months after mastectomy. Support Care Cancer 21:2453–2460CrossRef

23.

Rao S, Leung CS, Lam MH, Wing YK, Waye MM, Tsui SK (2017) Resequencing three candidate genes discovers seven potentially deleterious variants susceptibility to major depressive disorder and suicide attempts in Chinese. Gene 603:34–41. https://doi.org/10.1016/j.gene.2016.12.006 PubMedCrossRef

24.

Costafreda SG, McCann P, Saker P, Cole JH, Cohen-Woods S, Farmer AE, Aitchison KJ, McGuffin P, Fu CHY (2013) Modulation of amygdala response and connectivity in depression by serotonin transporter polymorphism and diagnosis. J Affect Disord 150(1):96–103PubMedCrossRef

25.

Manoharan A, Shewade DG, Rajkumar RP, Adithan S (2016) Serotonin transporter gene (SLC6A4) polymorphisms are associated with response to fluoxetine in south Indian major depressive disorder patients. Eur J Clin Pharmacol 72(10):1215–1220. https://doi.org/10.1007/s00228-016-2099-9 PubMedCrossRef

26.

Schinka JA, Busch RM, Robichaux-Keene N (2004) A meta-analysis of the association between the serotonin transporter gene polymorphism (5-HTTLPR) and trait anxiety. Mol Psychiatry 9(2):197–202PubMedCrossRef

27.

Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301(5631):386–389PubMedCrossRef

28.

Kaufman J, Yang BZ, Douglas-Palumberi H, Grasso D, Lipschitz D, Houshyar S, Krystal JH, Gelernter J (2006) Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental modifiers of depression in children. Biol Psychiatry 59(8):673–680PubMedCrossRef

29.

Kilpatrick DG et al (2007) The serotonin transporter genotype and social support and moderation of posttraumatic stress disorder and depression in hurricane-exposed adults. Am J Psychiatry 164(11):1693–1699PubMedCrossRef

30.

BIelinski M, Tomaszewska M, Jaracz M, Ulfig J, Diugosz D, Sikora M, Tretyn A, Kaminska A, Junik R, Borkowska A (2015) The polymorphisms in serotonin related genes and the prevelence of depressive symptoms in obese patients. Neurosci Lett 586:32–35CrossRef

31.

Gobbi M et al (2001) In vitro binding studies with two hypericum perforatum extracts--hyperforin, hypericin and biapigenin--on 5-HT6, 5-HT7, GABA(a)/benzodiazepine, sigma, NPY-Y1/Y2 receptors and dopamine transporters. Pharmacopsychiatry 34(Suppl 1):S45–S48PubMedCrossRef

32.

Karg K, Burmeister M, Shedden K, Sen S (2011) The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation. Arch Gen Psychiatry 68(5):444–454PubMedPubMedCentralCrossRef

33.

Taylor AE, Munafo MR (2016) (2016). Triangulating meta-analyses: the example of the serotonin transporter gene, stressful life events and major depression. Psychol Health Med 4(1):23

34.

Kim K, Chung H, Lee E, Kim S, Namkoong K (2012) Body image, sexual function and depression in Korean patients with breast cancer: modification by 5_HTT polymorphism. Support Care Cancer 20:2177–2182PubMedCrossRef

35.

Baker F, Haffer SC, Denniston M (2003) Health-related quality of life of cancer and noncancer patients in Medicare managed care. Cancer 97(3):674–681PubMedCrossRef

36.

Klein, M., et al. (2001). Neurobehavioral status and health-related quality of life in newly diagnosed high-grade glioma patients. [summary for patients in Curr Neurol Neurosci Rep 2002 May;2(3):203–4; PMID: 11936997]. J Clin Oncol, 19(20): 4037–47

37.

Frobe A et al (2014) Plasma free serotonin as a marker for early detection of breast cancer recurrence. Anticancer Res 34(3):1167–1169PubMed

38.

Sonier B, Arseneault M, Lavigne C, Ouellette RJ, Vaillancourt C (2006) The 5-HT2A serotoninergic receptor is expressed in the MCF-7 human breast cancer cell line and reveals a mitogenic effect of serotonin. Biochem Biophys Res Commun 343(4):1053–1059PubMedCrossRef

Title: Examining the effect of 5-HTTLPR on depressive symptoms in postmenopausal women 1 year after initial breast cancer treatment
Authors: Justine S. Wang
Yvette P. Conley
Susan M. Sereika
Catherine M. Bender
Poorwa Godbole
Susan W. Wesmiller
Publication date: 01-02-2019
Publisher: Springer Berlin Heidelberg
Published in: Supportive Care in Cancer / Issue 2/2019
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-018-4332-9

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Abstract

Background

Purpose

Methods

Conclusion

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