Advertisement

Relationship Between -2028 C/T SELP Gene Polymorphism, Concentration of Plasma P-Selectin and Risk of Malnutrition in Head and Neck Cancer Patients

  • Tomasz PowrózekEmail author
  • Radosław Mlak
  • Anna Brzozowska
  • Marcin Mazurek
  • Paweł Gołębiowski
  • Teresa Małecka-Massalska
Original Article
  • 43 Downloads

Abstract

Until today there is a lack of molecular factors, that could predict either cancer malnutrition or cachexia. Among potential mechanisms, that contribute to development of above syndromes, the systemic inflammatory response with overproduction of cytokines and adhesion molecules is the most likely. Recent papers suggested crucial role of P-selectin adhesion molecule in the initiation of leukocytes recruitment to the site of injury during inflammation, promotion of tumor aggressiveness and contribution to cancer cachexia. The aim of the study was to investigate SELP -2028 C/T polymorphism as a risk factor of malnutrition in 66 head and neck cancer (HNC) patients subjected to radiotherapy. Genotyping was conducted by real-time PCR method by means of TaqMan SNP Genotyping Assay. P-selectin Human ELISA Kit was used to determine P-selectin concentration in each extracted plasma samples. CC homozygous subjects had 4-fold higher risk score of being qualified as severely malnourished compared to other genotype carriers (p = 0.015). However, the TT homozygous patients were at lowest risk of severe weight loss >10% during the therapy period (OR = 0.20; p = 0.019). We also noted, that CC genotype carriers had significantly higher risk of early death incidence compared to CT or TT genotype (median survival time: 29 vs 34 months; HR = 3.02; p = 0.0085). Studied SELP -2028 C/T seems to be a novel attractive predictive factor of cancer malnutrition in HNC patients, perhaps in a future, patients carrying unfavorable CC genotype could be earlier scheduled for pharmaceutical intervention with parenterall nutrition, therefore they could be prevented from the development of severe malnutrition or even cachexia.

Keywords

Malnutrition Cachexia Head and neck cancer SELP P-selectin 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflict of interest.

Financial Disclosure

This study was not financially supported or funded.

Supplementary material

12253_2018_578_MOESM1_ESM.docx (26 kb)
ESM 1 (DOCX 25 kb)

References

  1. 1.
    O’Neill J, Shaha A (2011) Nutrition management of patients with malignancies of the head and neck. Surg Clin North Am 91:631–639CrossRefGoogle Scholar
  2. 2.
    Alshadwi A, Nadershah M, Carlson ER, Young LS, Burke PA, Daley BJ (2013) Nutritional considerations for head and neck cancer patients: a review of the literature. J Oral Maxillofac Surg 71(11):1853–1860CrossRefGoogle Scholar
  3. 3.
    Unsal D, Mentes B, Akmansu M, Uner A, Oguz M, Pak Y (2006) Evaluation of nutritional status in cancer patients receiving radiotherapy: a prospective study. Am J Clin Oncol 29:183–188CrossRefGoogle Scholar
  4. 4.
    Gorenc M, Kozjek NR, Strojana P (2015) Malnutrition and cachexia in patients with head and neck cancer treated with (chemo)radiotherapy. Rep Pract Oncol Radiother 20(4):249–258CrossRefGoogle Scholar
  5. 5.
    Dhanapal R, Saraswathi TR, Govind RN (2011) Cancer cachexia. J Oral Maxillofac Pathol 15(3):257–260CrossRefGoogle Scholar
  6. 6.
    Aoyagi T, Terracina KP, Raza A, Matsubara H, Takabe K (2015) Cancer cachexia, mechanism and treatment. World J Gastrointest Oncol 7(4):17–29CrossRefGoogle Scholar
  7. 7.
    Donohoe CL, Ryan AM, Reynolds JV (2011, 601434) Cancer Cachexia: mechanisms and clinical implications. Gastroenterol Res Pract 2011:1–13CrossRefGoogle Scholar
  8. 8.
    Imhof BA, Dunon D (1995) Leukocyte migration and adhesion. Adv Immunol 58:345–416CrossRefGoogle Scholar
  9. 9.
    Geng JG, Chen M, Chou KC (2004) P-selectin cell adhesion molecule in inflammation, thrombosis, cancer growth and metastasis. Curr Med Chem 11(16):2153–2160CrossRefGoogle Scholar
  10. 10.
    Reiner AP, Carlson CS, Thyagarajan B, Rieder MJ, Polak JF, Siscovick DS, Nickerson DA, Jacobs DR Jr, Gross MD (2008) Soluble P-selectin, SELP polymorphisms, and atherosclerotic risk in European-American and African-African young adults: the coronary artery risk development in young adults (CARDIA) study. Send to Arterioscler Thromb Vasc Biol 28(8):1549–1555CrossRefGoogle Scholar
  11. 11.
    Burkhardt J, Blume M, Petit-Teixeira E, Hugo Teixeira V, Steiner A, Quente E, Wolfram G, Scholz M, Pierlot C, Migliorini P, Bombardieri S, Balsa A, Westhovens R, Barrera P, Radstake TRDJ, Alves H, Bardin T, Prum B, Emmrich F, Cornelis F, Ahnert P, Kirsten H (2014) Cellular adhesion gene SELP is associated with rheumatoid arthritis and displays differential allelic expression. PLoS One 9(8):e103872CrossRefGoogle Scholar
  12. 12.
    Fearon KC, Glass DJ, Guttridge DC (2012) Cancer Cachexia: mediators, signaling, and metabolic pathways. Cell Metab 16(2):153–166CrossRefGoogle Scholar
  13. 13.
    Avan A, Avan A, Le Large TY et al (2014) AKT1 and SELP polymorphisms predict the risk of developing Cachexia in pancreatic Cancer patients. PLoS ONE 9(9):e108057CrossRefGoogle Scholar
  14. 14.
    Kaur R, Singh J, Kaur M (2017) Structural and functional impact of SNPs in P-selectin gene: a comprehensive in silico analysis. Open Life Sciences 12(1):19–33CrossRefGoogle Scholar
  15. 15.
    Volcik KA, Ballantyne CM, Coresh J, Folsom AR, Boerwinkle E (2007) Specific P-selectin and P-selectin glycoprotein ligand–1 genotypes/haplotypes are associated with risk of incident CHD and ischemic stroke: the atherosclerosis risk in communities (ARIC) study. Atherosclerosis 195:e76–e82CrossRefGoogle Scholar
  16. 16.
    Jacobin VM, Deramchia K, Mornet S et al (2011) MRI of inducible P-selectin expression in human activated platelets involved in the early stages of atherosclerosis. NMR Biomed 24:413–424Google Scholar
  17. 17.
    Miller MA, Kerry SM, Dong Y, Strazzullo P, Cappuccio FP (2004) Association between the Thr715Pro Pselectin gene polymorphism and soluble P-selectin levels in a multiethnic population in South London. Thromb Haemost 92:1060–1065CrossRefGoogle Scholar
  18. 18.
    Volcik KA, Ballantyne CM, Coresh J, Folsom AR, Wu KK, Boerwinkle E (2006) P-selectin Thr715Pro polymorphism predicts P-selectin levels but not risk of incident coronary heart disease or ischemic stroke in a cohort of 14595 participants: the atherosclerosis risk in communities study. Atherosclerosis 186:74–79CrossRefGoogle Scholar
  19. 19.
    Kou L, Yang N, Chen G et al (2016) Association of SELP genetic polymorphisms and additional gene-smoking interaction on cardiovascular disease in Chinese Han population. Int J Clin Exp Pathol 9(9):9612–9618Google Scholar
  20. 20.
    Morris DL, Graham RR, Erwig LP, Gaffney PM, Moser KL, Behrens TW, Vyse TJ, Graham DSC (2009) Variation in the upstream region of P-selectin (SELP) is a risk factor for SLE. Genes Immun 10:404–413CrossRefGoogle Scholar
  21. 21.
    Tan BH, Fladvad T, Braun TP et al (2012) P-selectin genotype is associated with the development of cancer cachexia. EMBO Mol Med 4(6):462–471CrossRefGoogle Scholar
  22. 22.
    Johns N, Stretch C, Tan BHL (2017) New genetic signatures associated with cancer cachexia as defined by low skeletal muscle index and weight loss. J Cachexia Sarcopenia Muscle 8(1):122–130CrossRefGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2019

Authors and Affiliations

  • Tomasz Powrózek
    • 1
    Email author
  • Radosław Mlak
    • 1
  • Anna Brzozowska
    • 2
  • Marcin Mazurek
    • 1
  • Paweł Gołębiowski
    • 2
  • Teresa Małecka-Massalska
    • 1
  1. 1.Department of Human PhysiologyMedical University of LublinLublinPoland
  2. 2.Department of OncologyMedical University of LublinLublinPoland

Personalised recommendations