oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2025-24-4-99-111oncotomsk-3772Research ArticleОБЗОРЫREVIEWSЭпидемиология и профилактика рака пищеводаEpidemiology and prevention of esophageal cancerhttps://orcid.org/0000-0002-2824-3704ЗаридзеД. Г.ZaridzeD. G.

Заридзе Давид Георгиевич, доктор медицинских наук, профессор, член-корреспондент РАН, руководитель отдела клинической эпидемиологии НИИ клинической онкологии им. акад. РАН и РАМН Н.Н. Трапезникова

Researcher ID (WOS): K-5605-2013. Author ID (Scopus): 7005676681 

115522, г. Москва, Каширское шоссе, 24 

David G. Zaridze, MD, DSc, Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Department of Clinical Epidemiology

Researcher ID (WOS): K-5605-2013. Author ID (Scopus): 7005676681 

24, Kashirskoe shosse, Moscow, 115522 

dgzaridze@rcs-pror.orgФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава РоссииРоссияN.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of RussiaRussian Federation20250110202524499111Copyright © Заридзе Д.Г., 20252025Заридзе Д.Г.Zaridze D.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/3772

Цель исследования – анализ заболеваемости и смертности от рака пищевода (РП) в мире и России; обзор литературы, посвященной этиологии и факторам риска РП. Материал и методы. Использованы базы данных GlOBOCan, «Рак на пяти континентах» и справочники МНИОИ им. П.А. Герцена по заболеваемости и смертности от злокачественных новообразований и состоянию онкологической помощи в России; проведен систематический поиск опубликованных работ в базах данных PubMed и Cochrane library. Результаты. Для РП характерна выраженная географическая вариабельность в заболеваемости. Высокие показатели заболеваемости зарегистрированы в странах Южной и ЮгоВосточной Азии, низкие – в Европе и Северной Америке. В России заболеваемость РП низкая. Однако в некоторых регионах этот показатель в 2 раза превышает общероссийский. В мире 85 % случаев РП имеют гистологическое строение плоскоклеточного рака (ПКР) и 14 % – аденокарциномы (АК). Плоскоклеточный РП встречается чаще в странах Восточной, Южной и Центральной Азии, АК превалирует в странах Северной Америки, Западной и Северной Европы. Заболеваемость от ПКР снижается, а заболеваемость АК растет. Доказанные факторы риска ПКР – курение, потребление алкоголя, горячего чая, опия, экспозиция к дыму горения биомассы (дров) в помещении, недостаток в диете овощей и фруктов. Основной фактор риска АК – избыточная масса тела. Риск АК повышен у лиц с диагнозом гастроэзофагеального рефлюкса (ГЭР) и эзофагита Барретта (ЭБ). идентифицированы соматические мутационные сигнатуры – результат экспозиции к основным факторам риска РП: табачному дыму, потреблению алкоголя, опия. Выявлены мутации, вызванные ферментами семейства aPOBeC. Профилактические меры, направленные на снижение распространенности перечисленных факторов риска ПКР, уже привели к снижению заболеваемости ПКР. Однако сохраняется необходимость продолжения активной профилактической работы, с учетом региональных особенностей. Профилактика АК, которая должна включать контроль избыточного веса, своевременную диагностику и лечение ГЭР и ЭБ, пока не очень эффективна. Заключение. Перечисленные факторы и связанные с ними сигнатуры не объясняют выраженную географическую вариабельность в заболеваемости РП. Для поиска неизвестных канцерогенных факторов с не мутационным, а эпигенетическим механизмом действия рекомендовано проведение дальнейших молекулярно-эпидемиологических исследований.

The aim of the study is to analyze incidence and mortality of esophageal cancer (EC) in the world and Russia; conduct a systematic review of literature of eC causes. Material and Methods. GlOBOCAN, Cancer Incidence in Five Continents and the annual Directories of Cancer Incidence and Mortality in Russia (MNIOI P.A. Hertsen) were used; a systematic search of the published papers on EC risk factors was carried out in the PubMed and Cochrane library databases. Results. EC is characterized by pronounced geographic variability in incidence. High incidence is noted in China, Mongolia, Iran. In Russia incidence of EC is low. In some regions, however, incidence is twice as high as in Russia overall. In the world, 85 % of EC cases have the histological structure of squamous cell carcinoma (SCC) and 14 % – adenocarcinoma (AC). SCC is more common in the countries of east, south and Central Asia, AC prevails in countries of north america, Western and northern europe. the incidence of SCC is decreasing, while incidence of aC is increasing. The main risk factors for SCC are smoking, consumption of alcohol, hot tea, opium, exposure to indoor biomass (wood) smoke, and dietary deficiency in vitamins and minerals. The main risk factor for AK is overweight. The risk of AC is increased in people with Gastro–eesophageal Reflux (GER) and Barrettes esophagus (BE). Molecular signatures caused by EC risk factors have been identified, including mutations, associated with tobacco smoking, alcohol consumption and opium use. Mutations caused by enzymes of the APOBEC family have also been discovered. Preventive measures aimed at reducing the prevalence of SCC risk factors, in particular, control of tobacco smoking, consumption of alcohol, diet modification have already led to a decrease in the incidence of EC. However, there remains a need to continue active preventive work, taking into account regional patterns. Prevention of AK, which should include control of excess weight, timely diagnosis and treatment of gastroesophageal reflux GER and BE, is not yet very effective. Conclusion. The described risk factors and associated mutational signatures do not explain the pronounced geographic variability in EC incidence. Further studies are needed to search for unknown carcinogenic factors with a non-mutational, but epigenetic mechanism of action.

плоскоклеточный рак пищеводааденокарциномаэпидемиологияпрофилактикафакторы рискамутационные сигнатурыsquamous cell cancerаdenocarcinomaepidemiologypreventionrisk factorsmutational signaturesReferencesGlobal Cancer Observatory (GLOBOCAN). Oesophagus. IARC, 2022. [Internet]. [cited 13.01.2025]. URL: https://gco.iarc.fr/en.Global Cancer Observatory (GLOBOCAN). Oesophagus. IARC, 2022. [Internet]. [cited 13.01.2025]. URL: https://gco.iarc.fr/en.Cancer Incidence in Five Continents. Vol. XII. Bray F., Colombet M., Aitken J.F., Bardot A., Eser S., Galceran J., Hagenimana M., Matsuda T., Mery L., Piñeros M., Soerjomataram I., de Vries E., Wiggins C., Won Y.-J., Znaor A., Ferlay J., editors (2023). (IARC CancerBase No. 19). Lyon: International Agency for Research on Cancer. [Internet]. [cited 13.01.2025]. URL: https://ci5.iarc.who.int.Cancer Incidence in Five Continents. Vol. XII. Bray F., Colombet M., Aitken J.F., Bardot A., Eser S., Galceran J., Hagenimana M., Matsuda T., Mery L., Piñeros M., Soerjomataram I., de Vries E., Wiggins C., Won Y.-J., Znaor A., Ferlay J., editors (2023). (IARC CancerBase No. 19). Lyon: International Agency for Research on Cancer. [Internet]. [cited 13.01.2025]. URL: https://ci5.iarc.who.int.Fan J., Liu Z., Mao X., Tong X., Zhang T., Suo C., Chen X. Global trends in the incidence and mortality of esophageal cancer from 1990 to 2017. Cancer Med. 2020; 9(18): 6875–87. doi: 10.1002/cam4.3338.Fan J., Liu Z., Mao X., Tong X., Zhang T., Suo C., Chen X. Global trends in the incidence and mortality of esophageal cancer from 1990 to 2017. Cancer Med. 2020; 9(18): 6875–87. doi: 10.1002/cam4.3338.Morgan E., Soerjomataram I., Rumgay H., Coleman H.G., Thrift A.P., Vignat J., Laversanne M., Ferlay J., Arnold M. The Global Landscape of Esophageal Squamous Cell Carcinoma and Esophageal Adenocarcinoma Incidence and Mortality in 2020 and Projections to 2040: New Estimates From GLOBOCAN 2020. Gastroenterology. 2022; 163(3): 649–58. doi: 10.1053/j.gastro.2022.05.054.Morgan E., Soerjomataram I., Rumgay H., Coleman H.G., Thrift A.P., Vignat J., Laversanne M., Ferlay J., Arnold M. The Global Landscape of Esophageal Squamous Cell Carcinoma and Esophageal Adenocarcinoma Incidence and Mortality in 2020 and Projections to 2040: New Estimates From GLOBOCAN 2020. Gastroenterology. 2022; 163(3): 649–58. doi: 10.1053/j.gastro.2022.05.054.Uhlenhopp D.J., Then E.O., Sunkara T., Gaduputi V. Epidemiology of esophageal cancer: update in global trends, etiology and risk factors. Clin J Gastroenterol. 2020; 13(6): 1010–21. doi: 10.1007/s12328-020-01237-x.Uhlenhopp D.J., Then E.O., Sunkara T., Gaduputi V. Epidemiology of esophageal cancer: update in global trends, etiology and risk factors. Clin J Gastroenterol. 2020; 13(6): 1010–21. doi: 10.1007/s12328-020-01237-x.Castro C., Bosetti C., Malvezzi M., Bertuccio P., Levi F., Negri E., La Vecchia C., Lunet N. Patterns and trends in esophageal cancer mortality and incidence in Europe (1980–2011) and predictions to 2015. Ann Oncol. 2014; 25(1): 283–90. doi: 10.1093/annonc/mdt486.Castro C., Bosetti C., Malvezzi M., Bertuccio P., Levi F., Negri E., La Vecchia C., Lunet N. Patterns and trends in esophageal cancer mortality and incidence in Europe (1980–2011) and predictions to 2015. Ann Oncol. 2014; 25(1): 283–90. doi: 10.1093/annonc/mdt486.Злокачественные новообразования в России в 2023 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, А.О. Шахзадовой. М., 2024. 276 с. ISBN: 978-5-85502-298-8.Malignant tumors in Russia in 2023 (morbidity and mortality). Ed. by A.D. Kaprin, V.V. Starinsky, A.O. Shakhzadova. Moscow, 2024. 276 p. (in Russian). ISBN: 978-5-85502-298-8.Tinusz B., Szapáry L.B., Paládi B., Papp A., Bogner B., Hegedűs I., Bellyei S., Vincze Á., Solt J., Micsik T., Dunás-Varga V., Pályu E., Vass T., Schnabel T., Farkas N., Hegyi P., Thrift A.P., Erőss B. The Esophageal Adenocarcinoma Epidemic Has Reached Hungary: A Multicenter, Cross-Sectional Study. Front Oncol. 2020; 10: 541794. doi: 10.3389/fonc.2020.541794.Tinusz B., Szapáry L.B., Paládi B., Papp A., Bogner B., Hegedűs I., Bellyei S., Vincze Á., Solt J., Micsik T., Dunás-Varga V., Pályu E., Vass T., Schnabel T., Farkas N., Hegyi P., Thrift A.P., Erőss B. The Esophageal Adenocarcinoma Epidemic Has Reached Hungary: A Multicenter, Cross-Sectional Study. Front Oncol. 2020; 10: 541794. doi: 10.3389/fonc.2020.541794.Петрова Г.В., Каприн А.Д., Грецова О.П., Старинский В.В. Злокачественные новообразования в России, обзор статистической информации за 1993–2013 гг. Под общей редакцией А.Д. Каприна, В.В. Старинского. М., 2015. 511 с. ISBN: 978-5-85502-215-5.Petrova G.V., Kaprin A.D., Gretsova O.P., Starinsky V.V. Malignant neoplasms in Russia, review of statistical information for 1993–2013. Ed. by A.D. Kaprin, V.V. Starinsky. Moscow, 2015. 511 p. (in Russian). ISBN: 978-5-85502-215-5.American Cancer Society. [Internet]. [cited 17.01.2025]. URL: www.cancer.org.American Cancer Society. [Internet]. [cited 17.01.2025]. URL: www.cancer.org.Cancer Research UK. [Internet]. [cited 17.01.2025]. URL: www. cancerresearchuk.org.Cancer Research UK. [Internet]. [cited 17.01.2025]. URL: www. cancerresearchuk.org.Состояние онкологической помощи населению России в 2023 году. Под ред. А.Д. Каприна, В.В. Старинского, А.О. Шахзадовой. М., 2024. 262 с. ISBN: 978-5-85502-297-1.Состояние онкологической помощи населению России в 2023 году. Под ред. А.Д. Каприна, В.В. Старинского, А.О. Шахзадовой. М., 2024. 262 с. [The state of oncological care for the population of Russia in 2023. Ed. by A.D. Kaprin, V.V. Starinsky, A.O. Shakhzadova. Moscow, 2024. 262 p. (in Russian)]. ISBN: 978-5-85502-297-1.Мерабишвили В.М., Беляев А.М. Состояние онкологической помощи в России: динамика пятилетней выживаемости больных злокачественными новообразованиями и ее ранговое распределение по всем локализациям опухолей. Популяционное исследование на уровне Северо-Западного федерального округа. Вопросы онкологии. 2023; 69(2): 227–37. doi: 10.37469/0507-3758-2023-69-2-227-237. EDN: SXCTME.Merabishvili V.M., Belyaev A.M. The state of oncology care in Russia: dynamics of five-year survival of patients with malignant neoplasms and its ranked distribution across all tumor sites. Population study at the level of the Northwestern Federal District of Russia. Problems in Oncology. 2023; 69(2): 227–37. (in Russian). doi: 10.37469/0507-3758-2023-69-2-227-237. EDN: SXCTME.Мерабишвили В.М., Беляев А.М. Состояние онкологической помощи в России: однолетняя выживаемость больных злокачественными новообразованиями и летальность на первом году жизни по всем локализациям опухолей. (Популяционное исследование на уровне федерального округа). Вопросы онкологии. 2023; 69(1): 55–66. doi: 10.37469/0507-3758-2023-69-1-55-66. EDN: KQQWIQ.Merabishvili V.M., Belyaev A.M. The state of cancer care in Russia: one-year survival rate of patients with malignant neoplasms and firstyear mortality rate for cancer of any site. (Population study at the federal district level). Problems in oncology. 2023; 69(1): 55–66. (in Russian). doi: 10.37469/0507-3758-2023-69-1-55-66. EDN: KQQWIQ.IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. (Personal habits and indoor combustions. Vol. 100E. Lyon, France, 2012. 575 p. ISBN: 978-92-832-1322-2).IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. (Personal habits and indoor combustions. Vol. 100E. Lyon, France, 2012. 575 p. ISBN: 978-92-832-1322-2).IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. (Alcohol Consumption and Ethyl Carbamate. Vol. 96. Lyon, France, 2010. 1424 p. ISBN: 978-92-832-1296-6).IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. (Alcohol Consumption and Ethyl Carbamate. Vol. 96. Lyon, France, 2010. 1424 p. ISBN: 978-92-832-1296-6).Заридзе Д.Г. Табак – основная причина рака. М., 2012. 208 с.Zaridze D.G. Tobacco is the main cause of cancer. Moscow, 2012. 208 p. (in Russian).Hashibe M., Boffetta P., Janout V., Zaridze D., Shangina O., Mates D., Szeszenia-Dabrowska N., Bencko V., Brennan P. Esophageal cancer in Central and Eastern Europe: tobacco and alcohol. Int J Cancer. 2007; 120(7): 1518–22. doi: 10.1002/ijc.22507.Hashibe M., Boffetta P., Janout V., Zaridze D., Shangina O., Mates D., Szeszenia-Dabrowska N., Bencko V., Brennan P. Esophageal cancer in Central and Eastern Europe: tobacco and alcohol. Int J Cancer. 2007; 120(7): 1518–22. doi: 10.1002/ijc.22507.Tian J., Zuo C., Liu G., Che P., Li G., Li X., Chen H. Cumulative Evidence for the Relationship between Body Mass Index and the Risk of Esophageal Cancer: An Updated Meta-Analysis with Evidence from 25 Observational Studies. J Gastroenterol Hepatol. 2020; 35(5): 730–43. doi: 10.1111/jgh.14917.Tian J., Zuo C., Liu G., Che P., Li G., Li X., Chen H. Cumulative Evidence for the Relationship between Body Mass Index and the Risk of Esophageal Cancer: An Updated Meta-Analysis with Evidence from 25 Observational Studies. J Gastroenterol Hepatol. 2020; 35(5): 730–43. doi: 10.1111/jgh.14917.Coleman H.G., Xie S.H., Lagergren J. The epidemiology of esophageal adenocarcinoma. Gastroenterology. 2018; 154(2): 390–405. doi: 10.1053/j.gastro.2017.07.046.Coleman H.G., Xie S.H., Lagergren J. The epidemiology of esophageal adenocarcinoma. Gastroenterology. 2018; 154(2): 390–405. doi: 10.1053/j.gastro.2017.07.046.Ye X.Y., Lai Y.T., Song W.P., Hu Y. The research progress on the association between dietary habits and esophageal cancer: a narrative review. Ann Palliat Med. 2021; 10(6): 6948–56. doi: 10.21037/apm-21-1467.Ye X.Y., Lai Y.T., Song W.P., Hu Y. The research progress on the association between dietary habits and esophageal cancer: a narrative review. Ann Palliat Med. 2021; 10(6): 6948–56. doi: 10.21037/apm-21-1467.Zhao Z., Wang F., Chen D., Zhang C. Red and Processed Meat сonsumption and Esophageal Cancer Risk: A Systematic Review and Meta-Analysis. Clin Transl Oncol. 2020; 22(4): 532–45. doi: 10.1007/s12094-019-02157-0.Zhao Z., Wang F., Chen D., Zhang C. Red and Processed Meat сonsumption and Esophageal Cancer Risk: A Systematic Review and Meta-Analysis. Clin Transl Oncol. 2020; 22(4): 532–45. doi: 10.1007/s12094-019-02157-0.Luo H., Ge H. Hot Tea Consumption and Esophageal Cancer Risk: A Meta-Analysis of Observational Studies. Front Nutr. 2022; 9: 831567. doi: 10.3389/fnut.2022.831567.Luo H., Ge H. Hot Tea Consumption and Esophageal Cancer Risk: A Meta-Analysis of Observational Studies. Front Nutr. 2022; 9: 831567. doi: 10.3389/fnut.2022.831567.Sheikh M., Shakeri R., Poustchi H., Pourshams A., Etemadi A., Islami F., Khoshnia M., Gharavi A., Roshandel G., Khademi H., Sepanlou S.G., Hashemian M., Fazel A., Zahedi M., Abedi-Ardekani B., Boffetta P., Dawsey S.M., Pharoah P.D., Sotoudeh M., Freedman N.D., Abnet C.C., Day N.E., Brennan P., Kamangar F., Malekzadeh R. Opium use and subsequent incidence of cancer: results from the Golestan Cohort Study. Lancet Glob Health. 2020; 8(5): 649–60. doi: 10.1016/S2214-109-X(20)30059-0.Sheikh M., Shakeri R., Poustchi H., Pourshams A., Etemadi A., Islami F., Khoshnia M., Gharavi A., Roshandel G., Khademi H., Sepanlou S.G., Hashemian M., Fazel A., Zahedi M., Abedi-Ardekani B., Boffetta P., Dawsey S.M., Pharoah P.D., Sotoudeh M., Freedman N.D., Abnet C.C., Day N.E., Brennan P., Kamangar F., Malekzadeh R. Opium use and subsequent incidence of cancer: results from the Golestan Cohort Study. Lancet Glob Health. 2020; 8(5): 649–60. doi: 10.1016/S2214-109-X(20)30059-0.Sheikh M., Poustchi H., Pourshams A., Khoshnia M., Gharavi A., Zahedi M., Roshandel G., Sepanlou S.G., Fazel A., Hashemian M., Abaei B., Sotoudeh M., Nikmanesh A., Merat S., Etemadi A., Moghaddam S.N., Islami F., Kamangar F., Pharoah P.D., Dawsey S.M., Abnet C.C., Boffetta P., Brennan P., Malekzadeh R. Household Fuel Use and the Risk of Gastrointestinal Cancers: The Golestan Cohort Study. Environ Health Perspect. 2020; 128(6): 67002. doi: 10.1289/EHP5907.Sheikh M., Poustchi H., Pourshams A., Khoshnia M., Gharavi A., Zahedi M., Roshandel G., Sepanlou S.G., Fazel A., Hashemian M., Abaei B., Sotoudeh M., Nikmanesh A., Merat S., Etemadi A., Moghaddam S.N., Islami F., Kamangar F., Pharoah P.D., Dawsey S.M., Abnet C.C., Boffetta P., Brennan P., Malekzadeh R. Household Fuel Use and the Risk of Gastrointestinal Cancers: The Golestan Cohort Study. Environ Health Perspect. 2020; 128(6): 67002. doi: 10.1289/EHP5907.Hardefeldt H.A., Cox M.R., Eslick G.D. Association between human papillomavirus (HPV) and oesophageal squamous cell carcinoma: a meta-analysis. Epidemiol Infect. 2014; 142(6): 1119–37. doi: 10.1017/S0950268814000016.Hardefeldt H.A., Cox M.R., Eslick G.D. Association between human papillomavirus (HPV) and oesophageal squamous cell carcinoma: a meta-analysis. Epidemiol Infect. 2014; 142(6): 1119–37. doi: 10.1017/S0950268814000016.van Nistelrooij A.M., Dinjens W.N., Wagner A., Spaander M.C., van Lanschot J.J., Wijnhoven B.P. Hereditary Factors in Esophageal Adenocarcinoma. Gastrointest Tumors. 2014; 1(2): 93–98. doi: 10.1159/000362575.van Nistelrooij A.M., Dinjens W.N., Wagner A., Spaander M.C., van Lanschot J.J., Wijnhoven B.P. Hereditary Factors in Esophageal Adenocarcinoma. Gastrointest Tumors. 2014; 1(2): 93–98. doi: 10.1159/000362575.Moody S., Senkin S., Islam S.M.A., Wang J., Nasrollahzadeh D., Cortez Cardoso Penha R., Fitzgerald S., Bergstrom E.N., Atkins J., He Y., Khandekar A., Smith-Byrne K., Carreira C., Gaborieau V., Latimer C., Thomas E., Abnizova I., Bucciarelli P.E., Jones D., Teague J.W., AbediArdekani B., Serra S., Scoazec J.Y., Saffar H., Azmoudeh-Ardalan F., Sotoudeh M., Nikmanesh A., Poustchi H., Niavarani A., Gharavi S., Eden M., Richman P., Campos L.S., Fitzgerald R.C., Ribeiro L.F., Soares-Lima S.C., Dzamalala C., Mmbaga B.T., Shibata T., Menya D., Goldstein A.M., Hu N., Malekzadeh R., Fazel A., McCormack V., McKay J., Perdomo S., Scelo G., Chanudet E., Humphreys L., Alexandrov L.B., Brennan P., Stratton M.R. Mutational signatures in esophageal squamous cell carcinoma from eight countries with varying incidence. Nat Genet. 2021; 53(11): 1553–63. doi: 10.1038/s41588-021-00928-6.Moody S., Senkin S., Islam S.M.A., Wang J., Nasrollahzadeh D., Cortez Cardoso Penha R., Fitzgerald S., Bergstrom E.N., Atkins J., He Y., Khandekar A., Smith-Byrne K., Carreira C., Gaborieau V., Latimer C., Thomas E., Abnizova I., Bucciarelli P.E., Jones D., Teague J.W., AbediArdekani B., Serra S., Scoazec J.Y., Saffar H., Azmoudeh-Ardalan F., Sotoudeh M., Nikmanesh A., Poustchi H., Niavarani A., Gharavi S., Eden M., Richman P., Campos L.S., Fitzgerald R.C., Ribeiro L.F., Soares-Lima S.C., Dzamalala C., Mmbaga B.T., Shibata T., Menya D., Goldstein A.M., Hu N., Malekzadeh R., Fazel A., McCormack V., McKay J., Perdomo S., Scelo G., Chanudet E., Humphreys L., Alexandrov L.B., Brennan P., Stratton M.R. Mutational signatures in esophageal squamous cell carcinoma from eight countries with varying incidence. Nat Genet. 2021; 53(11): 1553–63. doi: 10.1038/s41588-021-00928-6.Zhang J., Bellocco R., Sandborgh-Englund G., Yu J., Sällberg Chen M., Ye W. Poor Oral Health and Esophageal Cancer Risk: A Nationwide Cohort Study. Cancer Epidemiol Biomarkers Prev. 2022; 31(7): 1418–25. doi: 10.1158/1055-9965.EPI-22-0151.Zhang J., Bellocco R., Sandborgh-Englund G., Yu J., Sällberg Chen M., Ye W. Poor Oral Health and Esophageal Cancer Risk: A Nationwide Cohort Study. Cancer Epidemiol Biomarkers Prev. 2022; 31(7): 1418–25. doi: 10.1158/1055-9965.EPI-22-0151.Wang Q., Rao Y., Guo X., Liu N., Liu S., Wen P., Li S., Li Y. Oral Microbiome in Patients with Oesophageal Squamous Cell Carcinoma. Sci Rep. 2019; 9(1): 19055. doi: 10.1038/s41598-019-55667-w.Wang Q., Rao Y., Guo X., Liu N., Liu S., Wen P., Li S., Li Y. Oral Microbiome in Patients with Oesophageal Squamous Cell Carcinoma. Sci Rep. 2019; 9(1): 19055. doi: 10.1038/s41598-019-55667-w.Zhao Q., Yang T., Yan Y., Zhang Y., Li Z., Wang Y., Yang J., Xia Y., Xiao H., Han H., Zhang C., Xue W., Zhao H., Chen H., Wang B. Alterations of Oral Microbiota in Chinese Patients With Esophageal Cancer. Front Cell Infect Microbiol. 2020; 10: 541144. doi: 10.3389/fcimb.2020.541144.Zhao Q., Yang T., Yan Y., Zhang Y., Li Z., Wang Y., Yang J., Xia Y., Xiao H., Han H., Zhang C., Xue W., Zhao H., Chen H., Wang B. Alterations of Oral Microbiota in Chinese Patients With Esophageal Cancer. Front Cell Infect Microbiol. 2020; 10: 541144. doi: 10.3389/fcimb.2020.541144.Eusebi L.H., Telese A., Cirota G.G., Haidry R., Zagari R.M., Bazzoli F., Ford A.C. Effect of Gastro-Esophageal Reflux Symptoms on the Risk of Barrett’s Esophagus: A Systematic Review and Meta-Analysis. J Gastroenterol Hepatol. 2022; 37(8): 1507–16. doi: 10.1111/jgh.15902.Eusebi L.H., Telese A., Cirota G.G., Haidry R., Zagari R.M., Bazzoli F., Ford A.C. Effect of Gastro-Esophageal Reflux Symptoms on the Risk of Barrett’s Esophagus: A Systematic Review and Meta-Analysis. J Gastroenterol Hepatol. 2022; 37(8): 1507–16. doi: 10.1111/jgh.15902.Taylor P.R., Abnet C.C., Dawsey S.M. Squamous dysplasia – the precursor lesion for esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 2013; 22(4): 540–52. doi: 10.1158/1055-9965.EPI-12-1347.Taylor P.R., Abnet C.C., Dawsey S.M. Squamous dysplasia – the precursor lesion for esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 2013; 22(4): 540–52. doi: 10.1158/1055-9965.EPI-12-1347.Evstifeeva T.V., Zaridze D.G. Nass use, cigarette smoking, alcohol consumption and risk of oral and oesophageal precancer. Eur J Cancer B Oral Oncol. 1992; 28B(1): 29–35. doi: 10.1016/0964-1955(92)90008-o.Evstifeeva T.V., Zaridze D.G. Nass use, cigarette smoking, alcohol consumption and risk of oral and oesophageal precancer. Eur J Cancer B Oral Oncol. 1992; 28B(1): 29–35. doi: 10.1016/0964-1955(92)90008-o.Lu P., Gu J., Zhang N., Sun Y., Wang J. Risk factors for precancerous lesions of esophageal squamous cell carcinoma in high-risk areas of rural China: A population-based screening study. Medicine (Baltimore). 2020; 99(31): e21426. doi: 10.1097/MD.0000000000021426.Lu P., Gu J., Zhang N., Sun Y., Wang J. Risk factors for precancerous lesions of esophageal squamous cell carcinoma in high-risk areas of rural China: A population-based screening study. Medicine (Baltimore). 2020; 99(31): e21426. doi: 10.1097/MD.0000000000021426.Codipilly D.C., Qin Y., Dawsey S.M., Kisiel J., Topazian M., Ahlquist D., Iyer P.G. Screening for esophageal squamous cell carcinoma: recent advances. Gastrointest Endosc. 2018; 88(3): 413–26. doi: 10.1016/j.gie.2018.04.2352.Codipilly D.C., Qin Y., Dawsey S.M., Kisiel J., Topazian M., Ahlquist D., Iyer P.G. Screening for esophageal squamous cell carcinoma: recent advances. Gastrointest Endosc. 2018; 88(3): 413–26. doi: 10.1016/j.gie.2018.04.2352.Shaheen N.J., Falk G.W., Iyer P.G., Souza R.F., Yadlapati R.H., Sauer B.G., Wani S. Diagnosis and management of Barrett’s esophagus: an updated ACG guideline. Am J Gastroenterol. 2022; 117(4): 559–87. doi: 10.14309/ajg.0000000000001680.Shaheen N.J., Falk G.W., Iyer P.G., Souza R.F., Yadlapati R.H., Sauer B.G., Wani S. Diagnosis and management of Barrett’s esophagus: an updated ACG guideline. Am J Gastroenterol. 2022; 117(4): 559–87. doi: 10.14309/ajg.0000000000001680.Muñoz N., Wahrendorf J., Bang L.J., Crespi M., Thurnham D.I., Day N.E., Ji Z.H., Grassi A., Yan L.W., Lin L.G., et al. No effect of riboflavine, retinol, and zinc on prevalence of precancerous lesions of oesophagus. Randomised double-blind intervention study in high-risk population of China. Lancet. 1985; 2(8447): 111–14. doi: 10.1016/s0140-6736(85)90223-5.Muñoz N., Wahrendorf J., Bang L.J., Crespi M., Thurnham D.I., Day N.E., Ji Z.H., Grassi A., Yan L.W., Lin L.G., et al. No effect of riboflavine, retinol, and zinc on prevalence of precancerous lesions of oesophagus. Randomised double-blind intervention study in high-risk population of China. Lancet. 1985; 2(8447): 111–14. doi: 10.1016/s0140-6736(85)90223-5.Zaridze D., Evstifeeva T., Boyle P. Chemoprevention of oral leukoplakia and chronic esophagitis in an area of high incidence of oral and esophageal cancer. Ann Epidemiol. 1993; 3(3): 225–34. doi: 10.1016/1047-2797(93)90023-w.Zaridze D., Evstifeeva T., Boyle P. Chemoprevention of oral leukoplakia and chronic esophagitis in an area of high incidence of oral and esophageal cancer. Ann Epidemiol. 1993; 3(3): 225–34. doi: 10.1016/1047-2797(93)90023-w.Zhao Y., Guo C., Hu H., Zheng L., Ma J., Jiang L., Zhao E., Li H. Folate intake, serum folate levels and esophageal cancer risk: an overall and dose-response meta-analysis. Oncotarget. 2017; 8(6): 10458–69. doi: 10.18632/oncotarget.14432.Zhao Y., Guo C., Hu H., Zheng L., Ma J., Jiang L., Zhao E., Li H. Folate intake, serum folate levels and esophageal cancer risk: an overall and dose-response meta-analysis. Oncotarget. 2017; 8(6): 10458–69. doi: 10.18632/oncotarget.14432.Jankowski J.A.Z., de Caestecker J., Love S.B., Reilly G., Watson P., Sanders S., Ang Y., Morris D., Bhandari P., Brooks C., Attwood S., Harrison R., Barr H., Moayyedi P.; AspECT Trial Team. Esomeprazole and aspirin in Barrett’s oesophagus (AspECT): a randomised factorial trial. Lancet. 2018; 392(10145): 400–408. doi: 10.1016/S0140-6736(18)31388-6.Jankowski J.A.Z., de Caestecker J., Love S.B., Reilly G., Watson P., Sanders S., Ang Y., Morris D., Bhandari P., Brooks C., Attwood S., Harrison R., Barr H., Moayyedi P.; AspECT Trial Team. Esomeprazole and aspirin in Barrett’s oesophagus (AspECT): a randomised factorial trial. Lancet. 2018; 392(10145): 400–408. doi: 10.1016/S0140-6736(18)31388-6.Singh S., Singh A.G., Singh P.P., Murad M.H., Iyer P.G. Statins are associated with reduced risk of esophageal cancer, particularly in patients with Barrett’s esophagus: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2013; 11(6): 620–29. doi: 10.1016/j.cgh.2012.12.036.Singh S., Singh A.G., Singh P.P., Murad M.H., Iyer P.G. Statins are associated with reduced risk of esophageal cancer, particularly in patients with Barrett’s esophagus: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2013; 11(6): 620–29. doi: 10.1016/j.cgh.2012.12.036.

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