nogrЭкспериментальная и клиническая гастроэнтерологияExperimental and Clinical Gastroenterology1682-8658«Global Media Technologies»nogr-476Research ArticleКЛИНИЧЕСКАЯ ГАСТРОЭНТЕРОЛОГИЯCLINICAL GASTROENTEROLOGYПОЛИМОРФИЗМ ГЕНА IL1B В СИБИРСКОЙ ПОПУЛЯЦИИ АССОЦИИРОВАН С ПОВЫШЕННЫМ РИСКОМ РАЗВИТИЯ РАКА ЖЕЛУДКАIL1В POLYMORPHISM IS ASSOCIATED WITH AN INCREASED RISK OF GASTRIC CANCER IN THE POPULATION OF WESTERN SIBERIAБелковецА. В.BelkovetsA. V.belkovets@gmx.ruКуриловичС. А.KurilovichS. A.noemail@neicon.ruМаксимовВ. Н.MaksimovV. N.noemail@neicon.ruРагиноЮ. И.RaginoYu. I.noemail@neicon.ruЩербаковаЛ. В.ScherbakovaL. V.noemail@neicon.ruАлёшкинаА. В.AleschkinaA. V.noemail@neicon.ruВоеводаМ. И.VoevodaM. I.noemail@neicon.ruНаучно-исследовательский институт терапии и профилактической медицины» - филиал ФИЦ «Институт цитологии и генетики СО РАН»РоссияResearch Institute of Internal and Preventive Medicine - Branch of Institute of Cytology and Genetics SB RAN”Russian FederationНаучно-исследовательский институт терапии и профилактической медицины» - филиал ФИЦ «Институт цитологии и генетики СО РАН»; Новосибирский Государственный медицинский университет»РоссияNovosibirsk State Medical UniversityRussian Federation201720092017091017Copyright © Белковец А.В., Курилович С.А., Максимов В.Н., Рагино Ю.И., Щербакова Л.В., Алёшкина А.В., Воевода М.И., 20172017Белковец А.В., Курилович С.А., Максимов В.Н., Рагино Ю.И., Щербакова Л.В., Алёшкина А.В., Воевода М.И.Belkovets A.V., Kurilovich S.A., Maksimov V.N., Ragino Y.I., Scherbakova L.V., Aleschkina A.V., Voevoda M.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.nogr.org/jour/article/view/476

Сывороточные биомаркеры атрофического гастрита (пепсиноген I (ПГI) и соотношение ПГI/ПГII), являются прогностически важными для оценки риска развития рака желудка (РЖ). По данным ряда исследований полиморфизм гена IL1B также связан с риском развития РЖ. Цель исследования: изучить ассоциацию промоторного региона гена IL1B в позиции -511C/T (rs16944) с РЖ в проспективном исследовании «случай-контроль» (с глубиной проспекции 8 лет). Материалы и методы исследования: проведено сопоставление базы биоматериалов, полученных в 2003-2005 гг. в популяционной выборке жителей Новосибирска в рамках международного проекта HAPIEE(образцы ДНК и сыворотки хранились при -700С) с данными популяционного регистра РЖ (2012 г). Для каждого случая РЖ в соотношении 1:2 был подобран соответствующий по возрасту и полу контроль. В итоге, 156 образцов сыворотки крови (52 - РЖ, 104 - контроль) были проанализированы с помощью панели биомаркеров («ГастроПанель», Biohit, Финляндия) и 141 образец ДНК (49 - РЖ, 92 - контроль) прогенотипированы по опубликованной методике. Результаты: сравнительный анализ выявил достоверные различия для генотипа Т/Т, который чаще встречался в группе «случай» (16,3 %) в сравнении с группой «контроль» (5,4 %) (р=0,035). У лиц с генотипом Т/Т риск развития РЖ повышен в 3 раза (OR=3,4; СI: 1,0-11,0, р=0,03). Носители редкого аллеля Т имеют повышенный риск развития РЖ (OR=1,69; CI: 1,01-2,81, р=0,04), а распространенный аллель С обладает протективным эффектом в плане риска развития РЖ (OR=0,59; CI: 0,36-0,99, р=0,044). Средний показатель уровня ПГI и соотношения ПГI/ПГII статистически значимо меньше в группе «случай» при генотипе Т/Т: 41,3 ± 31,8 мкг/л и 4,1 ±2,9 в сравнении с группой «контроль»: 131,0 ± 57,2 мкг/л и 7,0±2,8 (р=0,004 и р=0,05, соответственно). Выводы: полиморфизм - 511C/T (rs16944) гена IL1В связан с формированием ракового фенотипа гастрита и может обсуждаться в рискометрии РЖ в комплексе с биомаркерами желудочной атрофии.

Background: Serum biomarkers of atrophic gastritis (pepsinogen I (PGI) and PGI/PGII ratio) are important for gastric cancer (GC) risk stratification. According to a number of researches IL1В gene polymorphisms are associated with risk of GC. The aim: to study the association of IL1В gene promoter polymorphism (-511C/T (rs16944) with GC in the prospective “case-control” study (8 years follow up). Materials and methods: the base of biomaterials received in 2003-2005 in population selection of residents of Novosibirsk within the international HAPIEE project (DNA samples and serums were stored at - 700C) were compared with data of the population register of GC (in 2012). For each case of GC, an appropriate control case was selected at the ratio 1:2 matching the area of residence, sex and age. Finally 156 serum samples (52 - GC group and 104 - control) were available for the analysis using a panel of serum biomarkers “Gastropanel” (Biohit, Finland) and 141 DNA samples (49 - GC group and 92 - control) were genotyped according to the published method. Results: the frequency of T/T genotype of the IL1В was found significantly higher in the GC group (16.3 %) compared with the control (5.4 %) (p=0.03). The T/T genotype was associated with significantly increased risks of GC compared with the C/C genotype (OR=3.4; СI: 1.0-11.0, р=0.03). It was shown that rare T allele carriers have increased risk GC development (OR=1.69; CI: 1.01-2.81, р=0.04) in comparison with wild C allele carriers (OR=0.59; CI: 0.36-0.99, р=0.04). The mean level of PGI and PGI/II ratio in persons with T/T genotype were significantly lower in GC group (41.3 ±31.8 µg/l and 4.1±2.9 versus 131.0±57.2 µg/l and 7.0±2.8; p=0.0001 and p=0.05 respectively). Conclusion: IL1В polymorphism (rs16944) is associated with an increased risk of GC in the population of Western Siberia and can be discussed for inclusion in the GC riskometer.

атрофический гастритрак желудкапепсиноген Iсоотношение ПГI/ПГIIполиморфизм гена IL1ВH. pyloriAtrophic gastritisgastric cancerpepsinogen IPGI/PGII ratioIL-1β polymorphismReferencesFerlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin D. M., Forman D. and Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5): E 359-86, 2015.Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin D. M., Forman D. and Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5): E 359-86, 2015.Давыдов М. И., Аксель Е. М. Статистика злокачественных новообразований в России и странах СНГ в 2012 году. М., 2014. - 226 с.Давыдов М. И., Аксель Е. М. Статистика злокачественных новообразований в России и странах СНГ в 2012 году. М., 2014. - 226 с.Davidov M. I., Aksel E. M. Statistics of neoplasias in Russia and SNG at 2012. M., 2014. - 226p.Davidov M. I., Aksel E. M. Statistics of neoplasias in Russia and SNG at 2012. M., 2014. - 226p.Openko TG, Reshetnikov OV, Kurilovich SA and Simonova GI. Gastric cancer in Novosibirsk at a turn of the millennium (trends of incidence and mortality, possibilities of prevention). Vopr Onkol 59: 708-713, 2013.Openko TG, Reshetnikov OV, Kurilovich SA and Simonova GI. Gastric cancer in Novosibirsk at a turn of the millennium (trends of incidence and mortality, possibilities of prevention). Vopr Onkol 59: 708-713, 2013.Sipponen P., Kekki M., Haapakoski J., Ihamäki T., Siurala M. Gastric cancer risk in chronic atrophic gastritis: statistical calculations of cross-sectional data. Int J Cancer, 1985, vol. 35, pp.173-177.Sipponen P., Kekki M., Haapakoski J., Ihamäki T., Siurala M. Gastric cancer risk in chronic atrophic gastritis: statistical calculations of cross-sectional data. Int J Cancer, 1985, vol. 35, pp.173-177.Vaananen H, Vauhkonen M, Helske T, et al. Nonendoscopic diagnosis of atrophic gastritis with a blood test. Correlation between gastric histology and serum levels of gastrin-17 and pepsinogen I: a multicentre study. Eur J Gastroenterol Hepatol 15: 885-891, 2003.Vaananen H, Vauhkonen M, Helske T, et al. Nonendoscopic diagnosis of atrophic gastritis with a blood test. Correlation between gastric histology and serum levels of gastrin-17 and pepsinogen I: a multicentre study. Eur J Gastroenterol Hepatol 15: 885-891, 2003.Syrjanen KJ, Sipponen P, Harkonen M, Peetsalu A and Korpela S. Accuracy of GastroPanel testing in detection of atrophic gastritis. Eur J Gastroenterol Hepatol 27: 102-104, 2015.Syrjanen KJ, Sipponen P, Harkonen M, Peetsalu A and Korpela S. Accuracy of GastroPanel testing in detection of atrophic gastritis. Eur J Gastroenterol Hepatol 27: 102-104, 2015.Oishi Y, Kiyohara Y, Kubo M, Tanaka K, Tanizaki Y, Ninomiya T, Doi Y, Shikata K, Yonemoto K, Shirota T, Matsumoto T and Iida M. The serum pepsinogen test as a predictor of gastric cancer: the Hisayama study. Am J Epidemiol 163: 629-637, 2006.Oishi Y, Kiyohara Y, Kubo M, Tanaka K, Tanizaki Y, Ninomiya T, Doi Y, Shikata K, Yonemoto K, Shirota T, Matsumoto T and Iida M. The serum pepsinogen test as a predictor of gastric cancer: the Hisayama study. Am J Epidemiol 163: 629-637, 2006.Маев И.В., Кучерявый Ю. А., Оганесян Т. С. Аллельный полиморфизм интерлейкина-1β при геликобактериозе. Российский журнал гастроэнтерологии, гепатологии и колопроктологии. 2008. 8: 4-11.Маев И.В., Кучерявый Ю. А., Оганесян Т. С. Аллельный полиморфизм интерлейкина-1β при геликобактериозе. Российский журнал гастроэнтерологии, гепатологии и колопроктологии. 2008. 8: 4-11.McColl K.E., El-Omar E., Gillen D. Helicobacter pylori gastritis and gastric physiology // Gastroenterol. Clin. North Am. - 2000. - Vol. 29. - P. 687-703.McColl K.E., El-Omar E., Gillen D. Helicobacter pylori gastritis and gastric physiology // Gastroenterol. Clin. North Am. - 2000. - Vol. 29. - P. 687-703.Schepp W., Dehne K., Herrmuth H. et al. Identification and functional importance of IL-1 receptors on rat parietal cells // Am. J. Physiol. - 1998. - Vol. 275. - P. 1094-1105.Schepp W., Dehne K., Herrmuth H. et al. Identification and functional importance of IL-1 receptors on rat parietal cells // Am. J. Physiol. - 1998. - Vol. 275. - P. 1094-1105.Saperas E., Yang H., Rivier C. et al. Central action of recombinant interleukin-1 to inhibit acid secretion in rats // Gastroenterology. - 1990. - Vol. 99. - P. 1599-1606.Saperas E., Yang H., Rivier C. et al. Central action of recombinant interleukin-1 to inhibit acid secretion in rats // Gastroenterology. - 1990. - Vol. 99. - P. 1599-1606.El-Omar E. M. The importance of interleukin 1beta in Helicobacter pylori associated disease // Gut. -2001. - Vol. 48. - P. 743-747.El-Omar E. M. The importance of interleukin 1beta in Helicobacter pylori associated disease // Gut. -2001. - Vol. 48. - P. 743-747.Wolfe M.M., Nompleggi D. J. Cytokine inhibition of gastric acid secretion little goes a long way // Gastroenterology. - 1992. - Vol. 102. - P. 2177-2178.Wolfe M.M., Nompleggi D. J. Cytokine inhibition of gastric acid secretion little goes a long way // Gastroenterology. - 1992. - Vol. 102. - P. 2177-2178.Bartchewsky W. Jr., Martini M. R., Masiero M., Squassoni A. C., Alvarez M. C., Ladeira M. S., Salvatore D., Trevisan M., Pedrazzoli J. Jr. Effect of Helicobacter pylori infection on IL-8, IL-1beta and COX- 2 expression in patients with chronic gastritis and gastric cancer. Scand. J. Gastroenterol. 2009; 44 (2): 153-161.Bartchewsky W. Jr., Martini M. R., Masiero M., Squassoni A. C., Alvarez M. C., Ladeira M. S., Salvatore D., Trevisan M., Pedrazzoli J. Jr. Effect of Helicobacter pylori infection on IL-8, IL-1beta and COX- 2 expression in patients with chronic gastritis and gastric cancer. Scand. J. Gastroenterol. 2009; 44 (2): 153-161.Bartchewsky W. Jr., Martini M. R., Masiero M., Squassoni A. C., Alvarez M. C., Ladeira M. S., Salvatore D., Trevisan M., Pedrazzoli J. Jr. Effect of Helicobacter pylori infection on IL-8, IL-1beta and COX- 2 expression in patients with chronic gastritis and gastric cancer. Scand. J. Gastroenterol. 2009; 44 (2): 153-161. 26.Bartchewsky W. Jr., Martini M. R., Masiero M., Squassoni A. C., Alvarez M. C., Ladeira M. S., Salvatore D., Trevisan M., Pedrazzoli J. Jr. Effect of Helicobacter pylori infection on IL-8, IL-1beta and COX- 2 expression in patients with chronic gastritis and gastric cancer. Scand. J. Gastroenterol. 2009; 44 (2): 153-161. 26.Hitzler I., Sayi A., Kohler E., Engler D. B., Koch K. N., Hardt W. D., Muller A. Caspase-1 has both proinflammatory and regulatory properties in Helicobacter infections, which are differentially mediated by its substrates IL-1β and IL-18. J. Immunol. 2012; 188 (8): 3594-3602.Hitzler I., Sayi A., Kohler E., Engler D. B., Koch K. N., Hardt W. D., Muller A. Caspase-1 has both proinflammatory and regulatory properties in Helicobacter infections, which are differentially mediated by its substrates IL-1β and IL-18. J. Immunol. 2012; 188 (8): 3594-3602.Tu S., Bhagat G., Cui G., Takaishi S., Kurt-Jones E.A., Rickman B., Betz K. S., Penz-Oesterreicher M., Bjorkdahl O., Fox J. G., Wang T. C. Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer cell. 2008; 14 (5): 408-419.Tu S., Bhagat G., Cui G., Takaishi S., Kurt-Jones E.A., Rickman B., Betz K. S., Penz-Oesterreicher M., Bjorkdahl O., Fox J. G., Wang T. C. Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer cell. 2008; 14 (5): 408-419.Berezhnaya N. M. Rol’ kletok sistemy immuniteta v mikrookruzhenii opukholi. II. Vzaimodeistvie kletok sistemy immuniteta s drugimi komponentami mikrookruzheniya. Onkolog. 2009; 11 (2): 86-93. 30.Berezhnaya N. M. Rol’ kletok sistemy immuniteta v mikrookruzhenii opukholi. II. Vzaimodeistvie kletok sistemy immuniteta s drugimi komponentami mikrookruzheniya. Onkolog. 2009; 11 (2): 86-93. 30.Macri A., Versaci A., Loddo S., Scuderi G., Travagliante M., Trimarchi G., Teti D., Famulari C. Serum levels of interleukin-1 beta, interleukin-8 and tumor necrosis factor alpha as markers of gastric cancer. Biomarcers. 2006; 11 (2): 184-193.Macri A., Versaci A., Loddo S., Scuderi G., Travagliante M., Trimarchi G., Teti D., Famulari C. Serum levels of interleukin-1 beta, interleukin-8 and tumor necrosis factor alpha as markers of gastric cancer. Biomarcers. 2006; 11 (2): 184-193.Gonzalez CA, Sala N, Capella G. Genetic susceptibility and gastric cancer risk. Int J Cancer 2004; 100: 249-260.Gonzalez CA, Sala N, Capella G. Genetic susceptibility and gastric cancer risk. Int J Cancer 2004; 100: 249-260.El-Omar EM, Carrington M, Chow WH et al. Interleukin-1 polymorphismsEl-Omar EM, Carrington M, Chow WH et al. Interleukin-1 polymorphismsJyh-Ming Liou et al. IL-1β-511 polymorphism is associated with increased host susceptibility to Helicobacter pylori infection in Chinese // Helicobacter. - 2007. -Vol. 12. - P. 142-149.Jyh-Ming Liou et al. IL-1β-511 polymorphism is associated with increased host susceptibility to Helicobacter pylori infection in Chinese // Helicobacter. - 2007. -Vol. 12. - P. 142-149.Machado J.C., Pharoah P., Sousa S. Interleukin-1β and interleukin-1RN polymorphisms are associated with increased risk of gastric carcinoma // Gastroenterology. - 2001. - Vol. 121, N 4. - P. 823-829.Machado J.C., Pharoah P., Sousa S. Interleukin-1β and interleukin-1RN polymorphisms are associated with increased risk of gastric carcinoma // Gastroenterology. - 2001. - Vol. 121, N 4. - P. 823-829.Rad R., Dossumbekova A., Neu B. et al. Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and host specific colonisation during Helicobacter pylori infection // Gut. - 2004. - Vol. 53. - P. 1082-1089.Rad R., Dossumbekova A., Neu B. et al. Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and host specific colonisation during Helicobacter pylori infection // Gut. - 2004. - Vol. 53. - P. 1082-1089.Garza-Gonzalez E., Bosques-Padilla F.J., El-Omar E.et al. Role of polymorphic IL-1B, IL-1RN, and TNFA genes in distal gastric cancer in Mexico // Int. J. Cancer. - 2005. - Vol. 114. - P. 237-241.Garza-Gonzalez E., Bosques-Padilla F.J., El-Omar E.et al. Role of polymorphic IL-1B, IL-1RN, and TNFA genes in distal gastric cancer in Mexico // Int. J. Cancer. - 2005. - Vol. 114. - P. 237-241.Farin Kamangar et al. Polymorphisms in inflammation related genes and risk of gastric cancer (Finland) //Cancer Causes Control. - 2006. - Vol. 17. - P. 117-125.Farin Kamangar et al. Polymorphisms in inflammation related genes and risk of gastric cancer (Finland) //Cancer Causes Control. - 2006. - Vol. 17. - P. 117-125.Matsukura N., Yamada S., Kato S. et al. Genetic differences in interleukin-1β polymorphisms among four Asian populations: an analysis of the Asian paradox between H. pylori infection and gastric cancer incidence // J. Exp. Clin. Cancer Res. - 2003. - Vol. 22. - P. 47-55.Matsukura N., Yamada S., Kato S. et al. Genetic differences in interleukin-1β polymorphisms among four Asian populations: an analysis of the Asian paradox between H. pylori infection and gastric cancer incidence // J. Exp. Clin. Cancer Res. - 2003. - Vol. 22. - P. 47-55.Manniatis T, Fritsch EF, Sambrook J (1982). Molecular cloning: A laboratory manual. Cold spring harbor, New York.Manniatis T, Fritsch EF, Sambrook J (1982). Molecular cloning: A laboratory manual. Cold spring harbor, New York.Zhang D. et al. Association of IL-1beta gene polymorphism with cachexia from locally advanced gastric cancer // BMC Cancer. - 2007. - N 7. - P. 45.Zhang D. et al. Association of IL-1beta gene polymorphism with cachexia from locally advanced gastric cancer // BMC Cancer. - 2007. - N 7. - P. 45.He C, Tu H, Sun L. et al. Helicobacter pylori-related host gene polymorphisms associated with susceptibility of gastric carcinogenesis: a two-stage case-control study in Chinese. Carcinogenesis. 2013;34:1450-7.He C, Tu H, Sun L. et al. Helicobacter pylori-related host gene polymorphisms associated with susceptibility of gastric carcinogenesis: a two-stage case-control study in Chinese. Carcinogenesis. 2013;34:1450-7.Решетников О.В., Курилович С. А., Кротов С. А., Кротова В. А. Хеликобактерная инфекция в Сибирских популяциях // Бюлл. СО РАМН. - 2010. - № 2. - С. 88-93.Решетников О.В., Курилович С. А., Кротов С. А., Кротова В. А. Хеликобактерная инфекция в Сибирских популяциях // Бюлл. СО РАМН. - 2010. - № 2. - С. 88-93.Reshetnikov O. V., Kurilovich S. A., Krotov C. A., Krotova V. A. Helicobacter Pylori-infection in Siberian Populations. Bull. SB RAMS, 2010; 2:88-93Reshetnikov O. V., Kurilovich S. A., Krotov C. A., Krotova V. A. Helicobacter Pylori-infection in Siberian Populations. Bull. SB RAMS, 2010; 2:88-93El-Omar E.M, Carrington M., Chow W. H., McColl K.E., Bream J. H., Young et al. The role of interleukin-1 polymorphisms in the pathogenesis of gastric cancer. Nature. 2001 Jul 5;412(6842):99.El-Omar E.M, Carrington M., Chow W. H., McColl K.E., Bream J. H., Young et al. The role of interleukin-1 polymorphisms in the pathogenesis of gastric cancer. Nature. 2001 Jul 5;412(6842):99.El-Omar E.M., Chow W. H., Gammon M. D. et al. Proinflammatory genotypes of IL-1beta, TNF-alpha and IL-10 increase risk of distal gastric cancer but not of cardia or oesophageal adenocarcinoma // Gastroenterology. - 2001. - Vol. 120, N 5 (suppl. 1). - P. 86.El-Omar E.M., Chow W. H., Gammon M. D. et al. Proinflammatory genotypes of IL-1beta, TNF-alpha and IL-10 increase risk of distal gastric cancer but not of cardia or oesophageal adenocarcinoma // Gastroenterology. - 2001. - Vol. 120, N 5 (suppl. 1). - P. 86.Yu J, Zeng Z, Wang S. et al. IL-1B-511 polymorphism is associated with increased risk of certain subtypes of gastric cancer in Chinese: a case-control study. Am J Gastroenterol. 2010;105:557-64.Yu J, Zeng Z, Wang S. et al. IL-1B-511 polymorphism is associated with increased risk of certain subtypes of gastric cancer in Chinese: a case-control study. Am J Gastroenterol. 2010;105:557-64.Chan A. O., Chu K. M., Huang C. et al. Association between Helicobacter pylori infection and interleukin 1beta polymorphism predispose to CpG island methylation in gastric cancer. Gut. 2007;56:595-7.Chan A. O., Chu K. M., Huang C. et al. Association between Helicobacter pylori infection and interleukin 1beta polymorphism predispose to CpG island methylation in gastric cancer. Gut. 2007;56:595-7.Zeng Z. R., Hu P. J., Hu S. et al. Association of interleukin 1B gene polymorphism and gastric cancers in high and low prevalence regions in China. Gut. 2003;52:1684-9.Zeng Z. R., Hu P. J., Hu S. et al. Association of interleukin 1B gene polymorphism and gastric cancers in high and low prevalence regions in China. Gut. 2003;52:1684-9.Kyoto global consensus report on Helicobacter pylori gastritis. Gut, 2015, vol. 64 (9), pp.1353-1367.Kyoto global consensus report on Helicobacter pylori gastritis. Gut, 2015, vol. 64 (9), pp.1353-1367.Kurilovich S., Belkovets A., Reshetnikov O., Openko T., Malyutina S., Ragino Y., Scherbakova L., Leja M., Paloheimo L., Syrjänen K., Voevoda M. Stomach-specific Biomarkers (GastroPanel) Can Predict the Development of Gastric Cancer in a Caucasian Population: A Longitudinal Nested Case-Control Study in Siberia. Anticancer Res. 2016 Jan;36(1):247-53.Kurilovich S., Belkovets A., Reshetnikov O., Openko T., Malyutina S., Ragino Y., Scherbakova L., Leja M., Paloheimo L., Syrjänen K., Voevoda M. Stomach-specific Biomarkers (GastroPanel) Can Predict the Development of Gastric Cancer in a Caucasian Population: A Longitudinal Nested Case-Control Study in Siberia. Anticancer Res. 2016 Jan;36(1):247-53.

The authors declare that there are no conflicts of interest present.