GENETIC DETERMINANTS OF PANCREATIC PATHOLOGY: A PILOT STUDY
About the author:
Muraviov P. T., Shevchenko V. G., Sharapov I. V., Bondaretz D. A., Volkov V. B.
Type of article:
The aim of the study was to evaluate the prevalence of mutations in the PRSS1, SPINK1, CFTR, and TNF genes in patients with chronic pancreatitis and pancreatic cancer. The study was performed during 2015-2019 at the Regional Clinical Medical Center (Odessa). Sixty inpatients at the surgical department were examined, including 30 persons with a verified diagnosis of pancreatic cancer (C25.9) – group I and 30 with a diagnosis of chronic pancreatitis (K86.1) – group II. All patients were examined and treated according to current clinical protocols. Biological material for molecular genetic testing was obtained by scraping the buccal epithelium. Analysis of the polymorphic DNA loci of the PRSS1, SPINK1, CFTR, and TNF genes was performed by PCR. The ratio of «wild» and mutant alleles in patients with pancreatic cancer was for the PRSS1 gene 28/3 = 7,3: 1, for the SPINK1 gene – 29/12 = 2,4: 1, for the CFTR gene – 30/9 = 3,3 : 1, for TNF gene – 28/11 = 2.5: 1. For patients with chronic pancreatitis – PRSS1 30/1 gene, for SPINK1 gene – 29/6 = 4.8: 1, for CFTR gene – 30/4 = 7.5: 1, for TNF gene – 30/6 = 2.5: 1. It is shown that carriers of mutant alleles of the PRSS1 gene are 10% of the examined patients suffering from pancreatic cancer, SPINK1 gene – 40.0%, CFTR – 30.0%, TNF 36.7%. The frequency of detection of mutant alleles in patients of group I is twice higher than in group II. The investigated PRSS1, SPINK1, CFTR, and TNF genes are closely related functionally to SERPINB8, SERPINI1, SMPD3, NR4A2, CYLD, F2RL1, TNFRSF1A, TNFRSF1B, CEBPA, SLC9A3R1, RFFL, CTRDA, F5RS1, RFFL, CTRDA, FNRF, CTRC, DNA, HRS PARD3, F2RL3.
chronic pancreatitis, pancreatic cancer, medical genetics, diagnostics.
- Shchastnyy AT. Khirurgicheskaya pankreatologiya. Vitebsk: VGMU; 2017. 98 s. [in Russian].
- Capasso M, Franceschi M, Rodriguez-Castro KI, Crafa P, Cambiè G, Miraglia C, et al. Epidemiology and risk factors of pancreatic cancer. Acta Biomed. 2018 Dec 17;89(9-S):141-6.
- Zou WB, Tang XY, Zhou DZ, Qian YY, Hu LH, Yu FF, et al. SPINK1, PRSS1, CTRC, and CFTR Genotypes Influence Disease Onset and Clinical Outcomes in Chronic Pancreatitis. Clin Transl Gastroenterol. 2018 Nov 12;9(11):204.
- Hasan A, Moscoso DI, Kastrinos F. The Role of Genetics in Pancreatitis. Gastrointest Endosc Clin N Am. 2018 Oct;28(4):587-603.
- Hohmann M, Schmelz R, Hampe J, Zeißig S. Sinnvolle genetische Untersuchungen in der Gastroenterologie. Dtsch Med Wochenschr. 2018 Oct;143(20):1477-80.
- Jancsó Z, Oracz G, Kujko AA, Kolodziejczyk E, Radisky ES, Rygiel AM, et al. Novel Pathogenic PRSS1 Variant p.Glu190Lys in a Case of Chronic Pancreatitis. Front Genet. 2019 Feb 6;10:46.
- The European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer, EUROPAC. Available from: https://www.lctu.org.uk/LCTU_ NET/Frontend/?Data=W1tiRzlqWVd4bF1dW09RPT1d
- Averbukh LD, Mavilia MG. SPINK-1 Polymorphism as a Pancreatitis Risk Factor. Cureus. 2019 Jan 8;11(1):e3852.
- Natsionalʹnyy Kantser-Reyestr. Rak pidshlunkovoyi zalozy. Dostupno: http://www.ncru.inf.ua/publications/BULL_20/PDF/34-35-podg.pdf [in Ukrainian].
- Braillon A. Screening for pancreatic cancer and scientific integrity. Gastrointest Endosc. 2018 Dec;88(6):971.
- Chhoda A, Lu L, Clerkin BM, Risch H, Farrell JJ. Current Approaches to Pancreatic Cancer Screening. Am J Pathol. 2019 Jan;189(1):22-35.
- DaVee T, Coronel E, Papafragkakis C, Thaiudom S, Lanke G, Chakinala RC, et al. Pancreatic cancer screening in high-risk individuals with germline genetic mutations. Gastrointest Endosc. 2018 Jun;87(6):1443-50.
- Welinsky S, Lucas AL. Familial Pancreatic Cancer and the Future of Directed Screening. Gut Liver. 2017 Nov 15;11(6):761-70.
- MKKh-10. Dostupno: https://www.icd10data.com/ [in Ukrainian].
- Asotsiatsiya khirurhiv Ukrayiny. Diyuchi normatyvni akty z pytanʹ khirurhiyi. Dostupno: http://as-ukr.org/diyuchi-normativni-akti-z-pitanhirurg/ [in Ukrainian].
- Dreyper Dzh, Skott R. Vydeleniye nukleinovykh kislot. Gennaya inzheneriya. Lab. ruk-vo: per. s angl. M.: Mir; 1991. s. 248-52. [in Russian].
Publication of the article:
«Bulletin of problems biology and medicine» Issue 4 Part 2 (154), 2019 year, 262-265 pages, index UDK 616.37-002.2:616.37-006.6:575.116