Relationship between catechol-o-methyltransferase gene polymorphism and pain syndrome in breast cancer patients

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

The goal of the study was to explore the influence of single-nucleotide polymorphisms of the COMT gene on the formation and features of pain syndrome, the level of anxiety, and the need for narcotic analgesics in patients with breast cancer.

Materials and methods. The intensity of pain and opioid consumption in the postoperative period were evaluated in 58 patients who met the inclusion criteria of the study and were operated for breast cancer. The frequency of chronic pain syndrome after mastectomy was studied in the same group of patients after a year by using short pain questionnaires, McGill Pain Questionnaire and PainDetect. The anxiety level was assessed by using the HADS questionnaire. Genotyping was performed for single-nucleotide polymorphisms, rs4680, rs740603, rs2097603 = rs2070577, rs4633, of the COMT gene localized in the 22q11.21 region in the studied group of patients. The relationship between the carrier of different genotypes and the intensity of acute and chronic pain, the severity of the pain rating index for sensory and affective characteristics, the presence of a neuropathic component of pain, and the severity of anxiety were studied in the entire sample. The use of narcotic analgesics was evaluated in the postoperative period (IU/day and IU/course) and for the relief of chronic pain.

Results. It is shown that the intensity of postoperative pain and the severity of anxiety do not depend on the presence of a mutant allele for the studied polymorphisms of the COMT gene, while the postoperative consumption of opioids in patients with the rs4680 missense mutation in the exon of this gene is significantly less. The dependence of the intensity of chronic pain syndrome and the severity of anxiety on the presence of a mutant allele for the polymorphic locus rs4680 localized in the exon of the COMT gene was established. No significant relationship was observed between the mutant alleles and the use of opioids for chronic pain relief after mastectomy.

Conclusion. Genotyping for the COMT gene polymorphisms can be useful for choosing the optimal tactics of pain management in patients with breast cancer.

Full Text

Restricted Access

About the authors

Arina P. Spasova

1Institute of Medicine, Petrozavodsk State University

Author for correspondence.
Email: arina22@mail.ru
ORCID iD: 0000-0002-2797-4740

MD, PhD, docent of the department of radiology and radiotherapy with a course of critical and respiratory medicine

Russian Federation, 185910, Petrozavodsk

I. V. Kurbatova

Institute of Biology, Karelian Research Center of Russian Academy of Sciences

Email: arina22@mail.ru
ORCID iD: 0000-0001-7620-7065
Russian Federation, 185910, Petrozavodsk

O. Y. Barysheva

Institute of Medicine, Petrozavodsk State University

Email: arina22@mail.ru
ORCID iD: 0000-0001-6317-1243
Russian Federation, 185910, Petrozavodsk

G. P. Tikhova

Institute of Medicine, Petrozavodsk State University

Email: arina22@mail.ru
ORCID iD: 0000-0003-1128-9666
Russian Federation, 185910, Petrozavodsk

References

  1. Kaprin A.D., Starinskiy V.V., Petrova G.V., eds. Status of oncological care for the population of Russia in 2017. www.oncology.ru Available at: http://www.oncology.ru/service/statistics/condition/2017.pdf (access 21 May 2020)
  2. Peuckmann V., Ekholm O., Rasmussen N.K., Groenvold M., Christiansen P., Moller S., Eriksen J., Sjogren P. Chronic pain and other sequelae in long-term breast cancer survivors: nationwide survey in Denmark. Eur. J. Pain. 2009;13:478-85. doi: 10.1016/S1043-321X(09)79400-7.
  3. Andresen K.G., Kehlet H. Persistent pain after breast cancer treatment: a critical review of risk factors and strategies for prevention. J. Pain. 2011;Jul;12(7):725-46. doi: 10.1016/j.jpain. 2010.12.005
  4. Ovechkin A.M. Chronic postoperative pain syndrome – the pitfall of modern surgery. Regionarnaya anesteziya i lechenie jsnroy boli. 2016;10(1):5-18. Doi: 1018821/1993-6508-2016-10-1-5-18.
  5. Wood K. Intercostobrachial nerve entrapment syndrome. South Med. J. 1978;71:662-3. doi: 10.1097/00007611-197806000- 00016.
  6. Granek I., Ashikari R., Foley K. The post-mastectomy pain syndrome: clinical and anatomical correlates. Proc. Am. Soc. Clin. Oncol. 1984;3:122.
  7. Vilholm O.J., Cold S., Rasmussen L., Sindrup S.H. The postmastectomy pain syndrome: an epidemiological study on the prevalence of chronic pain after surgery for breast cancer. Br. J. Cancer. 2008;99:604-10. doi: 10.1038/sj.bjc.6604534.
  8. Bredal I.S., Smeby N.A., Ottesen S., Warncke T., Schlich- ting E. Chronic pain in breast cancer survivors: Comparison of psychosocial, surgical, and medical characteristics between survivors with and without pain. J. Pain Sympt. Manage. 2014;48:852-62. doi: 10.1016/j.jpainsymman.2013.12.239.
  9. Harris S.R., Schmitz K.H., Campbell K.L., McNeely M.L. Clinical practice guidelines for breast cancer rehabilitation: Syntheses of guideline recommendations and qualitative appraisals. Cancer. 2012;118(8 Suppl):2312-24. doi: 10.1002/cncr.27461.
  10. Tait R.C., Zoberi K., Ferguson M. et al. Persistent Post-Mastectomy Pain: Risk Factors and Current Approaches to Treatment. J. Pain. 2018;19(12):1367-83. doi: 10.1016/j.jpain.2018.06.002.
  11. Mannisto P.T., Kaakkola S. Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors. Pharmacological reviews. 1999;51(4):593-628.
  12. Grossman M.H., Emanuel B.S., Budarf M.L. Chromosomal mapping of the human catechol-O-methyltransferase gene to 22q11.1–q11.2. Genomics. 1992;12:822-5. doi: 10.1016/0888-7543(92)90316-k.
  13. Lotta T., Vidgren J., Tilgmann C., Ulmanen I., Melen K., Julkunen I., Taskinen J. Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry. 1995;34(13):4202-10. doi: 10.1021/bi00013a008.
  14. Chen J., Lipska B., Halim N., Ma D. et al. Functional Analysis of Genetic Variation in Catechol-O-Methyltransferase (COMT): Effects on mRNA, Protein, and Enzyme Activity in Postmortem Human Brain. Am. J. Hum. Genet. 2004;Nov;75(5):807-21. doi: 10.1086/425589.
  15. Hoofwijk D.M., van Reij R.R., Rutten B.P., Kenis G., Buhre W.F., Joosten E.A. Genetic polymorphisms and their association with the prevalence and severity of chronic postsurgical pain: a systematic review. Brit. J. Anaesth. 2016;117:708-19. doi: 10.1093/bja/aew378.
  16. Tammimäki A., Männistö P.T. Catechol-O-methyltransferase gene polymorphism and chronic human pain: a systematic review and meta-analysis. Pharmacogenet. Genomics. 2012;22:673-91. doi: 10.1097/FPC.0b013e3283560c46.
  17. Zubieta J.K., Heitzeg M.M., Smith Y.R., Bueller J.A., Xu K., Xu Y., Koeppe R.A., Stohler C.S., Goldman D. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science. 2003;299(5610):1240-43. doi: 10.1126/science.1078546.
  18. Nackley A.G., Shabalina S.A., Tchivileva I.E., Satterfield K., Korchynskyi O., Makarov S.S., Diatchenko L. Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science. 2006;314:1930-33. doi: 10.1126/science.1131262.
  19. Yao P., Ding Y.Y., Wang Z.B., Ma J.M., Hong T., Pan S.N. Effect of gene polymorphism of COMT and OPRM1 on the preoperative pain sensitivity in patients with cancer. Int. J. Clin. Exp. Med. 2015;8:10036-9.
  20. Rakvåg T.T, Ross J.R., Sato H., Skorpen F., Kaasa S., Klepstad P. Genetic variation in the catechol-O-methyltransferase (COMT) gene and morphine requirements in cancer patients with pain. Mol. Pain. 2008;4:64. doi: 10.1186/1744-8069-4-64.
  21. Khalil H., Sereika S.M., Dai F., Alexander S., Conley Y., Gru- en G., Meng L., Siska P., Tarkin I., Henker R. OPRM1 and COMT Gene-Gene Interaction Is Associated With Postoperative Pain and Opioid Consumption After Orthopedic Trauma. Biol. Res. Nurs. 2017;19:170-79. doi: 10.1177/1099800416680474.
  22. Fernández-de-las-Peñas C., Fernández-Lao C., Cantarero-Villanueva I., Ambite-Quesada S., Rivas-Martínez I., del Moral-Avila R., Arroyo-Morales M. Catechol-O-methyltransferase genotype (Val158met) modulates cancer-related fatigue and pain sensitivity in breast cancer survivors. Breast Cancer Res. Tr. 2012;133:405-12. doi: 10.1007/s10549-011-1757-y.
  23. Coghill R.C., McHaffie J.G., Yen Y.F. Neural correlates of interindividual differences in the subjective experience of pain. Natl. Acad. Sci. USA. 2003;100(14):8538-42. doi: 10.1073/pnas.1430684100.
  24. Basbaum A.I., Fields H.L. Endogenous pain control mechanisms: review and hypothesis. Ann. Neurol. 1978;4(5):451-62. doi: 10.1002/ana.410040511.
  25. Wesmiller S.W., Sereika S.M., Bender C.M., Bovbjerg D., Ahrendt G., Bonaventura M., Conley Y.P. Exploring the multifactorial nature of postoperative nausea and vomiting in women following surgery for breast cancer. Auton. Neurosci. 2017;202:102-7. doi: 10.1016/j.autneu.2016.09.017.
  26. Henker R.A., Lewis A., Dai F., Lariviere W.R., Meng L., Gruen G.S., Sereika S.M., Pape H., Tarkin I.S., Gowda I., Conley Y.P. The associations between OPRM 1 and COMT genotypes and postoperative pain, opioid use, and opioid-induced sedation. Biol. Res. Nurs. 2013;15:309-17. doi: 10.1177/1099800411436171.
  27. Kambur O., Kaunisto M.A., Tikkanen E., Leal S.M., Ripatti S., Kalso E.A. Effect of catechol-o-methyltransferase-gene (COMT) variants on experimental and acute postoperative pain in 1,000 women undergoing surgery for breast cancer. Anesthesiology. 2013;119:1422-33. doi: 10.1097/ALN.0000000000000013.
  28. Kim H., Lee H., Rowan J., Brahim J., Dionne R.A. Genetic polymorphisms in monoamine neurotransmitter systems show only weak association with acute post-surgical pain in humans. Mol Pain. 2006;2:24. doi: 10.1186/1744-8069-2-24.
  29. Hu B., Zhang X., Xu G. et al. Association between COMT Polymorphism Val158Met and Opioid Consumption in Patients with Postoperative Pain: A Meta-Analysis. Neurosignals. 2018;26(1):11-21. doi: 10.1159/000487038.
  30. Matsuoka H., Arao T., Makimura C., Takeda M., Kiyota H., Tsurutani J., Nakagawa K. Expression changes in arrestin β1 and genetic variation in catechol-O-methyltransferase are biomarkers for the response to morphine treatment in cancer patients. Oncology Reports. 2012;27:1393-9. https://doi.org/10.3892/or.2012.1660.
  31. Ross J.R., Riley J., Taegetmeyer A.B., Sato H., Gretton S., du Bois R.M., Welsh K.I. Genetic variation and response to morphine in cancer patients: catechol-O-methyltransferase and multidrug resistance-1 gene polymorphisms are associated with central side effects. Cancer. 2008;112:1390-1403. doi: 10.1002/cncr.23292.
  32. Steiner H., Gerfen C.R. Role of dynorphin and enkephalin in the regulation of striatal output pathways and behavior. Exp. Brain Res. 1998;123:60-76. doi: 10.1007/s002210050545.
  33. Chen J.F., Aloyo V.J., Weiss B. Continuous treatment with the D2 dopamine receptor agonist quinpirole decreases D2 dopamine receptors, D2 dopamine receptor messenger RNA and proenkephalin messenger RNA, and increases mu opioid receptors in mouse striatum. Neuroscience. 1993;54:669-80. doi: 10.1016/0306-4522(93)90238-b.
  34. Hartung J.E., Ciszek B.P., Nackley A.G. β2- and β3-adrenergic receptors drive COMT-dependent pain by increasing production of nitric oxide and cytokines. Pain. 2014;155(7):1346-55. doi: 10.1016/j.pain.2014.04.011.
  35. Wang L., Guyatt G.H., Kennedy S.A. et al. Predictors of persistent pain after breast cancer surgery: a systematic review and meta-analysis of observational studies. CMAJ. 2016;188(14): E352–E361. doi: 10.1503/cmaj.151276.
  36. Vilholm O.J., Cold S., Rasmussen L., Sindrup S.H. Sensory function and pain in a population of patients treated for breast cancer. Acta Anaesthesiol. Scand. 2009;53:800-806. doi: 10.1111/j.1399-6576.2009.01938.x.
  37. Jensen K.B., Lonsdorf T.B., Schalling M., Kosek E., Ingvar M. Increased sensitivity to thermal pain following a single opiate dose is influenced by the COMT val(158)met polymorphism. PLoS One. 2009;4(6):e6016. doi: 10.1371/journal.pone.0006016.

Supplementary files

Supplementary Files
Action
1. Fig. 1. Consumption of opioids on the first postoperative day, depending on the genotype

Download (198KB)
2. Fig. 2. Consumption of opioids within 72 hours, depending on the genotype

Download (205KB)
3. Fig. 3. Frequency of localization of pain in persistent post-mastectomy pain

Download (98KB)
4. Fig. 4. Number of pain localization areas

Download (89KB)
5. Fig. 5. Intensity of persistent pain after mastectomy, depending on the genotype

Download (208KB)
6. Fig. 6. Assessment of pain syndrome according to the PainDetect questionnaire by COMT genotypes

Download (197KB)
7. Fig. 7. Rank index of pain for the sensory component of the McGill questionnaire for polymorphic loci of the COMT gene

Download (225KB)
8. Fig. 8. Assessment of anxiety depending on the genotype at the rs4680 locus of the COMT gene

Download (139KB)

Copyright (c) 2020 Eco-Vector



СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ ФС 77 - 55827 от 30.10.2013 г
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ЭЛ № ЭЛ № ФС 77 - 80651 от 15.03.2021 г
.



This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies