Факторы риска и некоторые аспекты канцеропревенции рака поджелудочной железы

Рак поджелудочной железы (РПЖ) - высокозлокачественная опухоль пищеварительной системы с плохим прогнозом. У большинства пациентов с РПЖ диагноз устанавливается на поздней стадии или при метастазировании из-за его агрессивных характеристик и отсутствия типичных ранних симптомов. Это ограничивает возможности лечения и обусловливает низкую пятилетнюю выживаемость в 3-15%. При этом РПЖ встречается относительно редко, и скрининг бессимптомного взрослого населения в настоящее время не считают целесообразным. Цель этого обзора - освещение основных направлений в разработке стратегии раннего скрининга РПЖ: выявление групп высокого риска и соответствующие методы, рекомендуемые для детального исследования в этих когортах.

рак поджелудочной железы, факторы риска, скрининг, методы визуализации поджелудочной железы, онкомаркеры, биомаркеры

1. Clinical guidelines. Pancreatic cancer. 2021. (in Russ.) Available at: https://cr.minzdrav.gov.ru/recomend/355_1@@ Клинические рекомендации. Рак поджелудочной железы. 2021. https://cr.minzdrav.gov.ru/recomend/355_1.

2. Yang J., Xu R., Wang C. et al. Early screening and diagnosis strategies of pancreatic cancer: a comprehensive review. Cancer Commun (Lond). 2021; 41(12): 1257-1274. doi: 10.1002/cac2.

3. Klein A.P. Pancreatic cancer epidemiology: understanding the role of lifestyle and inherited risk factors. Nat Rev Gastroenterol Hepatol. 2021; 18(7): 493-502. doi: 10.1038/s41575-021-00457-x.

4. Bray F., Ferlay J., Soerjomataram I. et al. A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. CA Cancer J Clin. 2020; 70(4): 313. doi: 10.3322/caac.21609.

5. Sung H., Ferlay J., Siegel R.L. et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3): 209-249. doi: 10.3322/caac.21660.

6. Siegel R.L., Miller K.D., Fuchs H.E., Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021; 71(1): 7-33. doi: 10.3322/caac.21669

7. Pereira S.P., Oldfield L., Ney A. et al. Early detection of pancreatic cancer. Lancet Gastroenterol Hepatol. 2020; 5(7): 698-710. doi: 10.1016/S2468-1253(19)30416-9.

8. Lindquist C.M., Miller F.H., Hammond N.A., Nikolaidis P. Pancreatic cancer screening. Abdom Radiol (NY). 2018; 43(2): 264-272. doi: 10.1007/s00261-017-1308-z.

9. Poruk K.E., Firpo M.A., Adler D.G., Mulvihill S.J. Screening for pancreatic cancer: why, how, and who? Ann Surg. 2013; 257: 17-26. doi: 10.1097/SLA.0b013e31825ffbfb.

10. Canto M.I., Hruban R.H., Fishman E.K. et al. Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. Gastroenterology. 2012; 142(4): 796-804. doi: 10.1053/j.gastro.2012.01.005.

11. Shi C., Klein A.P., Goggins M. et al. Increased prevalence of precursor lesions in familial pancreatic cancer patients. Clin. Cancer Res. 2009; 15: 7737-7743. doi: 10.1158/1078-0432.CCR-09-0004.

12. Hu C., Hart S.N., Polley E.C. et al. Association between inherited germline mutations in cancer predisposition genes and risk of pancreatic cancer. JAMA. 2018; 319: 2401-2409. doi: 10.1001/jama.2018.6228.

13. Goldstein A.M., Struewing J.P., Fraser M.C. et al. Prospective risk of cancer in CDKN2A germline mutation carriers. J. Med. Genet. 2004; 41: 421-424. doi: 10.1136/jmg.2004.019349.

14. Kastrinos F., Mukherjee B., Tayob N. et al. Risk of pancreatic cancer in families with Lynch syndrome. JAMA. 2009; 302: 1790-1795. doi: 10.1001/jama.2009.1529.

15. van Lier M.G., Wagner A., Mathus-Vliegen E.M. et al. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am.J. Gastroenterol. 2009; 105: 1258-1264. doi: 10.1038/ajg.2009.725.

16. Lin Y., Nakatochi M., Hosono Y. et al. Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer. Nat.Commun. 2020;11:3175. doi: 10.1038/s41467-020-16711-w.

17. Klein A.P., Wolpin B.M., Risch H.A. et al. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer. Nat.Commun. 2018; 9, 556. doi: 10.1038/s41467-018-02942-5.

18. Norris A.L., Roberts N.J., Jones S. et al. Familial and sporadic pancreatic cancer share the same molecular pathogenesis. Fam. Cancer. 2015; 14: 95-103. doi: 10.1007/s10689-014-9755-y.

19. Fogelman D., Sugar E.A., Oliver G. et al. Family history as a marker of platinum sensitivity in pancreatic adenocarcinoma. Cancer Chemother. Pharmacol. 2015; 76: 489-498. doi: 10.1007/s00280-015-2788-6.

20. Villarroel M.C., Rajeshkumar N.V., Garrido-Laguna I. et al. Personalizing cancer treatment in the age of global genomic analyses: PALB2 gene mutations and the response to DNA damaging agents in pancreatic cancer. Mol. Cancer Ther. 2011; 10: 3-8. doi: 10.1158/1535-7163.MCT-10-0893.

21. Goggins M., Overbeek K.A., Brand R. et al. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut. 2020; 69(1): 7-17. doi: 10.1136/gutjnl-2019-319352corr1.

22. Caban M, Małecka-Wojciesko E. Gaps and Opportunities in the Diagnosis and Treatment of Pancreatic Cancer. Cancers (Basel). 2023 Nov 25;15(23):5577. doi: 10.3390/cancers15235577.

23. Pang Y., Holmes M.V., Guo Y. et al. Smoking, alcohol, and diet in relation to risk of pancreatic cancer in China: a prospective study of 0.5 million people. Cancer Med. 2018; 7(1): 229-239. doi: 10.1002/cam4.1261.

24. Wood L.D. Hruban R.H. Pathology and molecular genetics of pancreatic neoplasms. Cancer J. 2012; 18: 492-501. doi: 10.1097/PPO.0b013e31827459b6.

25. Naudin S., Li K., Jaouen T. et al. Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study.Int J Cancer. 2018; 143(4): 801-812. doi: 10.1002/ijc.31367.

26. Yang, L., Zhou M., Sherliker P. et al. Alcohol drinking and overall and cause-specific mortality in China: nationally representative prospective study of 220 000 men with 15 years of follow-up.Int. J. Epidemiol. 2012; 41: 1101-1113. doi: 10.1093/ije/dys075.

27. McGuigan A., Kelly P., Turkington R.C. et al. Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes. World J Gastroenterol. 2018; 24(43): 4846-4861. doi: 10.3748/wjg.v24.i43.4846.

28. Antwi S.O., Eckert E.C., Sabaque C.V. et al. Exposure to environmental chemicals and heavy metals, and risk of pancreatic cancer. Cancer Causes Control. 2015; 26: 1583-1591. doi: 10.1007/s10552-015-0652-y.

29. Singhi A.D., Koay E.J., Chari S.T., Maitra A. Early Detection of Pancreatic Cancer: Opportunities and Challenges. Gastroenterology. 2019; 156(7): 2024-2040. doi: 10.1053/j.gastro.2019.01.259.

30. Raimondi S., Lowenfels A.B., Morselli-Labate A.M. et al. Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection. Best Pract Res Clin Gastroenterol. 2010;24:349-58. doi: 10.1016/j.bpg.2010.02.007.

31. Kirkegard J., Mortensen F.V., Cronin-Fenton D. Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis. Am J Gastroenterol. 2017; 112: 1366-1372. doi: 10.1038/ajg.2017.218.

32. Umans D.S., Hoogenboom S.A., Sissingh N.J. et al. Pancreatitis and pancreatic cancer: A case of the chicken or the egg. World J Gastroenterol. 2021; 27(23): 3148-3157. doi: 10.3748/wjg.v27.i23.3148.

33. Liu J., Wang Y., Yu Y. Meta-analysis reveals an association between acute pancreatitis and the risk of pancreatic cancer. World J Clin Cases. 2020; 8(19): 4416-4430. doi: 10.12998/wjcc.v8.i19.4416.

34. Pannala R., Leirness J.B., Bamlet W.R. et al. Prevalence and clinical profile of pancreatic cancer-associated diabetes mellitus. Gastroenterology. 2008; 134: 981-987. doi: 10.1053/j.gastro.2008.01.039.

35. Carreras-Torres R., Johansson M., Gaborieau V. et al. The role of obesity, type 2 diabetes, and metabolic factors in pancreatic cancer: a mendelian randomization study. J Natl Cancer Inst. 2017; 109(9): 495. doi: 10.1093/jnci/djx012.

36. Friedenreich C.M., Ryder-Burbidge C., McNeil J. Physical activity, obesity and sedentary behavior in cancer etiology: epidemiologic evidence and biologic mechanisms. Mol Oncol. 2021;15(3):790-800. doi: 10.1002/1878-0261.12772.

37. Yuan C., Babic A., Khalaf N. et al. Diabetes, weight change, and pancreatic cancer risk. JAMA Oncol. 2020; 6. doi:10.1001/jamaoncol.2020.2948.

38. Pang T.C., Lin T., Ding G. et al. Multiple factor analysis of pancreatic cancer-associated risk factors. Chin J Pract Surg. 2014;34(10):962-966.

39. Maisonneuve P., Amar S., Lowenfels A.B. Periodontal disease, edentulism, and pancreatic cancer: a meta-analysis. Ann. Oncol. 2017; 28: 985-995. doi: 10.1093/annonc/mdx019.

40. Gandini S., Lowenfels A.B., Jaffee E.M. et al. Allergies and the risk of pancreatic cancer: a meta-analysis with review of epidemiology and biological mechanisms. Cancer Epidemiol. Biomarkers Prev. 2005; 14: 1908-1916. doi: 10.1158/1055-9965.EPI-05-0119.

41. Memba R., Duggan S.N., Ni Chonchubhair H.M. et al. The potential role of gut microbiota in pancreatic disease: A systematic review. Pancreatology. 2017; 17: 867-874. doi: 10.1016/j.pan.2017.09.002.

42. Schulte A., Pandeya N., Fawcett J. et al. Association between Helicobacter pylori and pancreatic cancer risk: a meta-analysis. Cancer Causes Control. 2015; 26: 1027-1035. doi: 10.1007/s10552-015-0595-3.

43. European Study Group on Cystic Tumours of the Pancreas. European evidence-based guidelines on pancreatic cystic neoplasms. Gut. 2018; 67(5): 789-804. doi: 10.1136/gutjnl-2018-316027.

44. Springer S., Wang Y., Dal Molin M. et al. A combination of molecular markers and clinical features improve the classification of pancreatic cysts. Gastroenterology. 2015; 149: 1501-1510. doi: 10.1053/j.gastro.2015.07.041.

45. Baranova I.B. Diagnostics of pancreatic cysts in fine-needle aspiration biopsy (FNAB) samples.Russian News of Clinical Cytology. 2020; 24(3): 19-30. (In Russ.) doi:10.24412/1562-4943-2020-3-0004.@@ Баранова И.Б. Диагностика кистозных образований поджелудочной железы. Исследование материала, полученного методом ТИАБ. Новости клинической цитологии России. 2020; 24(3): 19-30. doi:10.24412/ 1562-4943-2020-3-0004.

46. Farr K.P., Moses D., Haghighi K.S. et al. Imaging Modalities for Early Detection of Pancreatic Cancer: Current State and Future Research Opportunities. Cancers (Basel). 2022; 14(10): 2539. doi: 10.3390/cancers14102539.

47. Peters M.L.B., Eckel A., Mueller P.P. et al. Progression to pancreatic ductal adenocarcinoma from pancreatic intraepithelial neoplasia: Results of a simulation model. Pancreatology. 2018; 18(8): 928-934. doi: 10.1016/j.pan.2018.07.009.

48. He M., Xue H., Jin Z., Zhao Y. State-of-the art imaging in the diagnosis and treatment of pancreatic ductal carcinoma: current role and value. Medical Journal of Peking Union Medical College Hospital. 2019; 10(1): 11-8.

49. Ashida R., Tanaka S., Yamanaka H. et al. The Role of Transabdominal Ultrasound in the Diagnosis of Early Stage Pancreatic Cancer: Review and Single-Center Experience. Diagnostics (Basel). 2018; 9(1): 2. doi: 10.3390/diagnostics9010002.

50. Tanaka S., Nakaizumi A., Ioka T. et al. Periodic ultrasonography checkup for the early detection of pancreatic cancer: preliminary report. Pancreas. 2004; 28(3): 268-72. doi: 10.1097/00006676-200404000-00010.

51. Toft J., Hadden W.J., Laurence J.M. et al. Imaging modalities in the diagnosis of pancreatic adenocarcinoma: A systematic review and meta-analysis of sensitivity, specificity and diagnostic accuracy. Eur. J. Radiol. 2017; 92: 17-23. doi: 10.1016/j.ejrad.2017.04.009.

52. Puli S.R., Bechtold M.L., Buxbaum J.L., Eloubeidi M.A. How good is endoscopic ultrasound-guided fine-needle aspiration in diagnosing the correct etiology for a solid pancreatic mass? A meta-analysis and systematic review. Pancreas. 2013; 42: 20-26. doi: 10.1097/MPA.0b013e3182546e79.

53. Tanaka M., Fernández-Del Castillo C., Kamisawa T. et al. Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology. 2017; 17(5): 738-753. doi: 10.1016/j.pan.2017.07.007.

54. Vege S.S., Ziring B., Jain R., Moayyedi P. Clinical Guidelines Committee; American Gastroenterology Association. American gastroenterological association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology. 2015; 148(4):819-22. doi: 10.1053/j.gastro.2015.01.015.

55. O’Neill R.S. Stoita A. Biomarkers in the diagnosis of pancreatic cancer: Are we closer to finding the golden ticket? World J Gastroenterol. 2021; 27(26): 4045-4087. doi: 10.3748/wjg.v27.i26.4045.

56. Luo G., Guo M., Jin K. et al. Optimize CA19-9 in detecting pancreatic cancer by Lewis and Secretor genotyping. Pancreatology. 2016; 16(6): 1057-1062. doi: 10.1016/j.pan.2016.09.013.

57. Deng G., Yan H., Guo Z., Dai G. Relationship between CA199 and prognosis of patients with advanced pancreatic cancer. Academic Journal of Chinese PLA Medical School. 2019; 40(1): 33-36.

58. Xing H., Wang J., Wang Y. et al. Diagnostic value of CA 19-9 and carcinoembryonic antigen for pancreatic cancer: a meta-analysis. 2018. doi: 10.1155/2018/8704751.

59. Gu Y.L., Lan C., Pei H. et al. Applicative value of serum CA19-9, CEA, CA125 and CA242 in diagnosis and prognosis for patients with pancreatic cancer treated by concurrent chemoradiotherapy. Asian Pac J Cancer Prev. 2015; 16(15): 6569-6573. doi: 10.7314/apjcp.2015.16.15.6569.

60. Chen J.C., Beal E.W., Pawlik T.M. et al. Molecular Diagnosis of Cystic Neoplasms of the Pancreas: a Review. 2020; 24(5): 1201-1214. doi: 10.1007/s11605-020-04537-2.