nogrЭкспериментальная и клиническая гастроэнтерологияExperimental and Clinical Gastroenterology1682-8658«Global Media Technologies»10.31146/1682-8658-ecg-182-10-25-32nogr-1446Research ArticleКЛИНИЧЕСКАЯ ГАСТРОЭНТЕРОЛОГИЯCLINICAL GASTROENTEROLOGYГенетический полиморфизм провоспалительных цитокинов IL-1β и IL-6 у пациентов с серологически выявленным атрофическим гастритомGenetic polymorphism of the infl ammatory cytokines IL-1β and IL-6 in patients with serologically identifi ed atrophic gastritisБелковецА. В.BelkovetsA. V.

630089, г. Новосибирск, ул. Б. Богаткова, 175/1

Российская Федерация, 630091, г. Новосибирск, Красный проспект, 52

doctor of medical sciences, head of the clinic, senior researcher of laboratory of gastroenterology

630089, Novosibirsk, B. Bogatkova str., 175/1

630091, Novosibirsk, Krasnyj prospect, 52

belkovets@gmx.deКуриловичС. А.KurilovichS. A.

630089, г. Новосибирск, ул. Б. Богаткова, 175/1

Российская Федерация, 630091, г. Новосибирск, Красный проспект, 52

doctor of medical sciences, professor, head of laboratory of gastroenterology

630089, Novosibirsk, B. Bogatkova str., 175/1

630091, Novosibirsk, Krasnyj prospect, 52

МаксимовВ. Н.MaksimovV. N.

д. м. н., профессор, заведующий лабораторией молекулярно-генетических исследований терапевтических заболеваний

630089, г. Новосибирск, ул. Б. Богаткова, 175/1

Российская Федерация, 630091, г. Новосибирск, Красный проспект, 52

doctor of medical sciences, professor, head of laboratory of molecular genetic studies of therapeutic diseases

630089, Novosibirsk, B. Bogatkova str., 175/1

630091, Novosibirsk, Krasnyj prospect, 52

ЩербаковаЛ. В.ScherbakovaL. V.

старший научный сотрудник лаборатории клинико-популяционных и профилактических исследований терапевтических и эндокринных заболеваний

 630089, г. Новосибирск, ул. Б. Богаткова, 175/1

senior researcher of laboratory of clinical-populational and prophylactic studies of Internal and Endocrine Diseases

630089, Novosibirsk, B. Bogatkova str., 175/1

НИИТПМ — филиал Федерального государственного бюджетного научного учреждения «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»; ФГБОУ ВО Новосибирский государственный медицинский университет Минздрава РоссииРоссияIIPM — Branch of the Federal State Budget Scientifi c Institution “The Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences”; Federal State Budget Educational Institution of Higher Education “Novosibirsk State Medical University” Ministry of Health of the Russian FederationRussian FederationНИИТПМ — филиал Федерального государственного бюджетного научного учреждения «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»РоссияIIPM — Branch of the Federal State Budget Scientifi c Institution “The Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences”Russian Federation2020271020200102532Copyright © Белковец А.В., Курилович С.А., Максимов В.Н., Щербакова Л.В., 20202020Белковец А.В., Курилович С.А., Максимов В.Н., Щербакова Л.В.Belkovets A.V., Kurilovich S.A., Maksimov V.N., Scherbakova L.V.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/1446Актуальность

Актуальность: некоторыми исследователями продемонстрирована связь генетического полиморфизма некоторых провоспалительных цитокинов (IL-1β, IL-6) с риском развития предраковых заболеваний желудка и рака желудка (РЖ).

Целью исследования было изучить частоты генотипов и аллелей полиморфизмов –511C/T (rs16944) гена IL1В и 174G/C (rs1800795) гена IL6 у пациентов с серологически выявленным атрофическим гастритом (АГ) — основным предраковым заболеванием желудка.

Материалы и методы

Материалы и методы: в исследование вошли 55 человек (45 женщин и 10 мужчин) со средним возрастом 58,2 ± 11,5 лет с признаками явной или возможной атрофии разных отделов слизистой оболочки желудка, выявленной иммуноферментным анализом (ИФА) с определением уровней пепсиногена I, II (ПГI, ПГII), их соотношения, гастрина-17 и IgG антител к H.рylori с помощью набора диагностикумов «ГастроПанель» (Biohit Plc, Helsinski, Finland). ДНК выделяли из венозной крови с помощью метода фенол-хлороформной экстракции. Образцы ДНК прогенотипированы по опубликованным  методикам.

Результаты

Результаты: у пациентов с выраженным АГ (уровень ПГI менее 30 мг/л) объединённый вариант с редким аллелем Т (Т/Т + С/Т) был выявлен достоверно чаще (68,8%), чем распространённый гомозиготный вариант С/С (31,3%, р=0,004). У лиц с низким соотношением ПГI/ПГII (менее 3), что также является свидетельством фундальной  атрофии, гомозиготный вариант Т/Т встречался чаще (29,6%), чем генотип С/С (7,4%,  р=0,04). Средние показатели ПГI оказались достоверно ниже при С/С генотипе гена IL6 в сравнении с гетерозиготным вариантом С/G (р=0,03), однако у пациентов с морфологически подтверждённой атрофией объединённый вариант с редким аллелем G (G/G+C/G) гена IL6 встречался чаще, чем гомозиготный вариант С/С (71,4% против 28,6%, р=001).

Выводы

Выводы: у пациентов с признаками фундальной атрофии (низкий показатель ПГI,  соотношения ПГI/ПГII) гомозиготный вариант с редким аллелем Т, с которым связывают  повышенную продукцию IL-1β и развитие гипоацидного состояния, встречался в 4 раза чаще, чем гомозиготный вариант С/С (р=0,04). Полученные результаты позволяют предполагать возможную связь полиморфизма IL1B (носительство редкого Т аллеля) с формированием ракового фенотипа гастрита. Вклад полиморфизма IL6 требует дальнейшего уточнения.

Background

Background: some researchers have demonstrated a link between the genetic polymorphism of certain pro-infl ammatory cytokines (IL-1β, IL-6) and the risk of developing precancerous diseases of the stomach and gastric cancer (GC).

Aim

Aim: to study the genotypes and alleles frequency of polymorphisms of –511C/T (rs16944) of the IL1B gene and 174G/C (rs1800795) of the IL6 gene in patients with serologically detected atrophic gastritis (AG) — the main precancerous lesions of the stomach.

Materials and methods

Materials and methods. the study included 55 people (45 females and10 males) with an average age of 58.2 ± 11.5 years with signs of obvious or possible atrophy of diff erent parts of the gastric mucosa revealed by enzyme-linked immunosorbent assay (ELISA) with determination of pepsinogen levels I (PGI), PGII, the PGI / PGII ratio, gastrin-17 and IgG antibodies to H. pylori using the “GastroPanel” diagnostic kit (Biohit Plc, Helsinski, Finland). DNA was isolated from venous blood using the phenol-chloroform extraction method. DNA samples were genotyped according to published methods.

Results

Results: in patients with severe AG (PGI level less than 30 μg/l), the combined variant with the rare T allele (T/T + C/T) was detected signifi cantly more often (68.8%) than the common homozygous C/C variant (31, 3%, p = 0.004). In individuals with a low PGI/PGII ratio (less than 3), which is also evidence of fundamental atrophy, the homozygous T/T variant was more common (29.6%) than the C/C genotype (7.4%, p = 0.04) The average PGI values were signifi cantly lower with the C/C genotype of the IL-6 gene compared with the heterozygous C/G variant (p = 0.03), however, in patients with morphologically confi rmed atrophy, the  combined variant with the rare G allele (G/G + C/G) of the IL6 gene was more common than the homozygous C/C variant (71.4% versus 28.6%, p = 001).

Conclusions

Conclusions: in patients with signs of corpus atrophy (low PGI, PGI PGII ratios), the homozygous variant with a rare T allele, which is associated with increased IL-1β production and the development of a hypoacid state, was 4 times more likely than the homozygous C/C variant (p = 0.04). The results obtained suggest a possible association of IL1B polymorphism (carriage of a rare T allele) with the formation of a cancer phenotype of gastritis. The contribution of IL6 polymorphism requires further refi nement.

атрофический гастритполиморфизмrs1800795rs16944IL-6IL-1ВпепсиногеныH.pyloriatrophic gastritispolymorphismrs1800795rs16944IL-6IL-1BpepsinogenesH. pyloriReferencesFerlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, Znaor A, Bray F. Estimating the global cancer incidence and mortality in 2018. GLOBOCAN sources and methods. Int J Cancer, 2019, 144, рр.1941–1953.Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, Znaor A, Bray F. Estimating the global cancer incidence and mortality in 2018. GLOBOCAN sources and methods. Int J Cancer, 2019, 144, рр.1941–1953.Correa P. Human gastric carcinogenesis: a multistep and multifactorial process. First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res., 1992, vol. 52(24), pp. 6735–40.Correa P. Human gastric carcinogenesis: a multistep and multifactorial process. First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res., 1992, vol. 52(24), pp. 6735–40.Salim D.K., Sahin M., Koksoy S et al. Local Immune Response in Helicobacter pylori Infection. Medicine (Baltimore), 2016, vol. 95(20), pp.1–8.Salim D.K., Sahin M., Koksoy S et al. Local Immune Response in Helicobacter pylori Infection. Medicine (Baltimore), 2016, vol. 95(20), pp.1–8.Kim J.Y., Bae B. N., Kang G. et al. Cytokine expression associated with Helicobacter pylori and Epstein-Barr virus infection in gastric carcinogenesis. APMIS, 2017, vol. 25(9), pp. 808–815.Kim J.Y., Bae B. N., Kang G. et al. Cytokine expression associated with Helicobacter pylori and Epstein-Barr virus infection in gastric carcinogenesis. APMIS, 2017, vol. 25(9), pp. 808–815.Graham D. Y. Helicobacter pylori update: gastric cancer, reliable therapy, and possible benefits. Gastroenterology, 2015, vol.148, pp. 719–31.Graham D. Y. Helicobacter pylori update: gastric cancer, reliable therapy, and possible benefits. Gastroenterology, 2015, vol.148, pp. 719–31.Del Prete A., Allavena P., Santoro G., Fumarulo R., Corsi M. M., Mantovani A. Molecular pathways in cancer-related infl ammation. Biochem Med (Zagreb), 2011, vol.21, pp. 264–275.Del Prete A., Allavena P., Santoro G., Fumarulo R., Corsi M. M., Mantovani A. Molecular pathways in cancer-related infl ammation. Biochem Med (Zagreb), 2011, vol.21, pp. 264–275.Multhoff G., Radons J. Radiation, infl ammation, and immune responses in cancer. Front Oncol. 2012, 2:58.Multhoff G., Radons J. Radiation, infl ammation, and immune responses in cancer. Front Oncol. 2012, 2:58.Qu X., Tang Y., Hua S. Immunological Approaches Towards Cancer and Inflammation: A Cross Talk. Front Immunol, 2018, 9:563.Qu X., Tang Y., Hua S. Immunological Approaches Towards Cancer and Inflammation: A Cross Talk. Front Immunol, 2018, 9:563.Hussain S.P., Harris C. C. Inflammation and cancer: an ancient link with novel potentials. Int J Cancer, 2007, vol.121, pp. 2373–2380.Hussain S.P., Harris C. C. Inflammation and cancer: an ancient link with novel potentials. Int J Cancer, 2007, vol.121, pp. 2373–2380.Gigek C.O., Calcagno D. Q., Rasmussen L. T., Santos L. C., Leal M. F. et al. Genetic variants in gastric cancer: Risks and clinical implications. Exp Mol Pathol, 2017, vol.103, pp.101–111.Gigek C.O., Calcagno D. Q., Rasmussen L. T., Santos L. C., Leal M. F. et al. Genetic variants in gastric cancer: Risks and clinical implications. Exp Mol Pathol, 2017, vol.103, pp.101–111.Hosono K., Yamada E., Endo H., Takahashi H., Inamori M. et al. Increased tumor necrosis factor receptor 1 expression in human colorectal adenomas. World J Gastroenterol, 2012, vol.18, pp. 5360–5368.Hosono K., Yamada E., Endo H., Takahashi H., Inamori M. et al. Increased tumor necrosis factor receptor 1 expression in human colorectal adenomas. World J Gastroenterol, 2012, vol.18, pp. 5360–5368.Agréus L., Kuipers E..J, Kupcinskas L., Malfertheiner P. et al. Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers. Scand J Gastroenterol, 2012, vol. 47(2), pp. 136–147.Agréus L., Kuipers E..J, Kupcinskas L., Malfertheiner P. et al. Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers. Scand J Gastroenterol, 2012, vol. 47(2), pp. 136–147.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.Negovan A., Iancu М., Fülöp E., Bănescu C. Helicobacter pylori and cytokine gene variants as predictors of premalignant gastric lesions. World J Gastroenterol, 2019, vol.25(30), pp. 4105–4124.Negovan A., Iancu М., Fülöp E., Bănescu C. Helicobacter pylori and cytokine gene variants as predictors of premalignant gastric lesions. World J Gastroenterol, 2019, vol.25(30), pp. 4105–4124.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, pp. 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, pp. 1094–1105.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.Maev I. V., Kucheryavyy Yu. A., Oganesyan T. S. Allelic polymorphism of interleukin-1β in helicobacteriosis. Russian journal of gastroenterology, hepatology and coloproctology. 2008; 8: 4–11.Hitzler I., Sayi A., Kohler E., Engler D. B. et al. 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, vol. 188 (8), pp. 3594–3602.Hitzler I., Sayi A., Kohler E., Engler D. B. et al. 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, vol. 188 (8), pp. 3594–3602.Gonzalez C.A., Sala N., Capella G. Genetic susceptibility and gastric cancer risk. Int J Cancer, 2004, vol. 100, pp. 249–260.Gonzalez C.A., Sala N., Capella G. Genetic susceptibility and gastric cancer risk. Int J Cancer, 2004, vol. 100, pp. 249–260.El-Omar E.M., Carrington M., Chow W. H., McColl K.E., Bream J. H. et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature, 2000, vol. 404, pp. 398–402.El-Omar E.M., Carrington M., Chow W. H., McColl K.E., Bream J. H. et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature, 2000, vol. 404, pp. 398–402.Gehmert S., Velapatiño B., Herrera P., Balqui J., Santivañez L. et al. Interleukin-1 beta single-nucleotide polymorphism’s C allele is associated with elevated risk of gastric cancer in Helicobacter pylori-infected Peruvians. Am J Trop Med Hyg., 2009, vol. 81, pp. 804–810.Gehmert S., Velapatiño B., Herrera P., Balqui J., Santivañez L. et al. Interleukin-1 beta single-nucleotide polymorphism’s C allele is associated with elevated risk of gastric cancer in Helicobacter pylori-infected Peruvians. Am J Trop Med Hyg., 2009, vol. 81, pp. 804–810.Leja M., Wex T., Malfertheiner P. Markers for gastric cancer premalignant lesions: where do we go? Dig Dis, 2012, vol.30, pp. 268–276.Leja M., Wex T., Malfertheiner P. Markers for gastric cancer premalignant lesions: where do we go? Dig Dis, 2012, vol.30, pp. 268–276.Romano M., Sironi M., Toniatti C., Polentarutti N. et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity.1997, vol. 6, pp. 315–325.Romano M., Sironi M., Toniatti C., Polentarutti N. et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity.1997, vol. 6, pp. 315–325.Fishman D., Faulds G., Jeffery R., Mohamed-Ali V., Yudkin J. S. et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest., 1998, vol.102, pp.1369–1376.Fishman D., Faulds G., Jeffery R., Mohamed-Ali V., Yudkin J. S. et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest., 1998, vol.102, pp.1369–1376.Yamaoka Y., Kita M., Kodama T., Sawai N., Imanishi J. Helicobacter pylori cagA gene and expression of cytokine messenger RNA in gastric mucosa. Gastroenterology, 1996, vol. 110, pp. 1744–1752.Yamaoka Y., Kita M., Kodama T., Sawai N., Imanishi J. Helicobacter pylori cagA gene and expression of cytokine messenger RNA in gastric mucosa. Gastroenterology, 1996, vol. 110, pp. 1744–1752.Sampaio A.M., Balseiro S. C., Silva M. R., Alarcão A., d’Aguiar M.J. et al. Association Between IL-4 and IL-6 Expression Variants and Gastric Cancer Among Portuguese Population. GE Port J Gastroenterol, 2015, vol. 22, pp.143–152.Sampaio A.M., Balseiro S. C., Silva M. R., Alarcão A., d’Aguiar M.J. et al. Association Between IL-4 and IL-6 Expression Variants and Gastric Cancer Among Portuguese Population. GE Port J Gastroenterol, 2015, vol. 22, pp.143–152.Crusius J.B., Canzian F., Capellá G. et al. Cytokine gene polymorphisms and the risk of adenocarcinoma of the stomach in the European prospective investigation into cancer and nutrition (EPIC-EURGAST) Ann Oncol, 2008, vol. 19, pp. 1894–1902.Crusius J.B., Canzian F., Capellá G. et al. Cytokine gene polymorphisms and the risk of adenocarcinoma of the stomach in the European prospective investigation into cancer and nutrition (EPIC-EURGAST) Ann Oncol, 2008, vol. 19, pp. 1894–1902.Manniatis T., Fritsch E. F., Sambrook J. (1982). Molecular cloning: A laboratory manual. Cold spring harbor, New York.Manniatis T., Fritsch E. F., 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, vol.7, pp.45.Zhang D. et al. Association of IL-1beta gene polymorphism with cachexia from locally advanced gastric cancer. BMC Cancer, 2007, vol.7, pp.45.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, vol. 11 (2), pp. 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, vol. 11 (2), pp. 184–193.Белковец А.В., Курилович С. А., Максимов В. Н., Рагино Ю. И., Щербакова Л. В., Алёшкина А. В., Черемисина О. В., Чердынцева Н. В., Воевода М. И. Полиморфизм гена IL1B в сибирской популяции ассоциирован с повышенным риском развития рака желудка. Экспериментальная и клиническая гастроэнтерология, 2017, vol. 145(9), pp. 10–17.Belkovets A. V., Kurilovich S. A., Maksimov V. N., Ragino Yu.I., et al. IL1В polymorphism is associated with an increased risk of gastric cancer in the population of western siberia. Experimental and Clinical Gastroenterology. 2017;(9):10–17. (In Russ.)Hnatyszyn A., Wielgus K., Kaczmarek-Rys M. et al. Interleukin-1 Gene Polymorphisms in Chronic Gastritis Patients Infected with Helicobacter pylori as Risk Factors of Gastric Cancer Development. Arch. Immunol. Ther. Exp., 2013, vol. 61, pp. 503–512.Hnatyszyn A., Wielgus K., Kaczmarek-Rys M. et al. Interleukin-1 Gene Polymorphisms in Chronic Gastritis Patients Infected with Helicobacter pylori as Risk Factors of Gastric Cancer Development. Arch. Immunol. Ther. Exp., 2013, vol. 61, pp. 503–512.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, vol. 34, pp.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, vol. 34, pp.1450–7.Bennermo M., Held C., Stemme S., Ericsson C. G. et al. Genetic predisposition of the interleukin-6 response to inflammation: implications for a variety of major diseases? Clin Chem., 2004, vol. 50(11), pp. 2136–40.Bennermo M., Held C., Stemme S., Ericsson C. G. et al. Genetic predisposition of the interleukin-6 response to inflammation: implications for a variety of major diseases? Clin Chem., 2004, vol. 50(11), pp. 2136–40.Hwang I.R., Hsu P. I., Peterson L. E., Gutierrez O. et al. Interleukin-6 genetic polymorphisms are not related to Helicobacter pylori associated gastroduodenal diseases. Helicobacter, 2003, vol. 8, pp. 142–8.Hwang I.R., Hsu P. I., Peterson L. E., Gutierrez O. et al. Interleukin-6 genetic polymorphisms are not related to Helicobacter pylori associated gastroduodenal diseases. Helicobacter, 2003, vol. 8, pp. 142–8.Pohjanen V.M., Koivurova O. P., Mäkinen J. M., Karhukorpi J. M. et al. Interleukin 6 gene polymorphism – 174 is associated with the diffuse type gastric carcinoma. Genes Chromosomes Cancer, 2013, vol. 52(10), pp. 976–82.Pohjanen V.M., Koivurova O. P., Mäkinen J. M., Karhukorpi J. M. et al. Interleukin 6 gene polymorphism – 174 is associated with the diffuse type gastric carcinoma. Genes Chromosomes Cancer, 2013, vol. 52(10), pp. 976–82.Gatti L.L, Burbano R.R, Zambaldi-Tunes M., de-Lábio R.W., de Assumpção P. P. et al. Interleukin-6 polymorphisms, Helicobacter pylori infection in adult Brazilian patients with chronic gastritis and gastric adenocarcinoma. Arch Med Res., 2007, vol. 38, pp. 551–555. 551–555.Gatti L.L, Burbano R.R, Zambaldi-Tunes M., de-Lábio R.W., de Assumpção P. P. et al. Interleukin-6 polymorphisms, Helicobacter pylori infection in adult Brazilian patients with chronic gastritis and gastric adenocarcinoma. Arch Med Res., 2007, vol. 38, pp. 551–555.

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