Association between cytokine gene polymorphisms and squamous cell lung cancer depending on the duration of smoking in men

Cover Page

Cite item

Full Text

Abstract

Background. Squamous cell lung cancer (SCLC) is the most common form of lung cancer among men smokers. Mediators and products of inflammation can contribute to the initiation of carcinogenesis in smokers. The aim of study is to investigate the association between IL1B(rs1143634, rs16944), IL1RN (rs2234663), TNFA (rs1800629), IL6 (rs1800795), IL10 (rs1800896) genes and SCLC depending on the duration of smoking in men.

Materials and methods. We studied 324 patients with SCLC and 168 healthy men smokers. The typing of the IL1RN(rs2234663) gene polymorphism has analyzed by polymerase chain reaction (PCR). Detection of the IL1B (rs1143634) and IL6 (rs1800795) polymorphisms have performed by restriction fragment length analysis, as a restriction enzyme TaqI was used. The IL1B (rs16944), TNFA(rs1800629) and IL10 (rs1800896) genes polymorphisms have determined through TaqMan-real-time PCR.

Results. The study showed, the age, duration of smoking and the number of cigarettes smoked per day were the main risk factors for SCLC in men (p < 0.0001). The IL6 -174G allele was detected an additional risk factor of SCLC at a smoking duration of less than 35 years (OR = 1.68; 95 % CI: 1.12-2.51; pcor = 0,04). No association of IL1B (rs1143634, rs16944), IL1RN (rs2234663), TNFA (rs1800629), and IL10 (rs1800896) genes with the risk of SCLC in men was identified.

Conclusion. The duration of smoking and rs1800795 IL6 gene polymorphism may influence on the susceptibility to SCLC in men. Our results can be useful in understanding the molecular mechanisms of development of SCLC.

About the authors

Lyudmila A. Gordeeva

FRC CCC SB RAS (Institute of Human Ecology SB RAS)

Author for correspondence.
Email: gorsib@rambler.ru

PhD, Leading Rof the Laboratory Immunogenetics

Russian Federation, Kemerovo

Stella A. Mun

FRC CCC SB RAS (Institute of Human Ecology SB RAS)

Email: stellamun@yandex.ru

PhD, Senior Researcher of the Laboratory Immunogenetics

Kemerovo

Elena N. Voronina

Institute of Chemical Biology and Fundamental Medicine SB RAS

Email: voronina_l@mail.ru

PhD, Researcher of the Laboratory Pharmacogenomics

Russian Federation, Novosibirsk

Elena G. Polenok

FRC CCC SB RAS (Institute of Human Ecology SB RAS)

Email: ihe@list.ru

PhD, Leading Researcher of the Laboratory Immunochemistry

Russian Federation, Kemerovo

Alina D. Magatina

Regional Clinical Hospital

Email: ihe@kemtel.ru

Biologist of the Genetic Consultation

Russian Federation, Kemerovo

Viktor A. Titov

Regional Clinical Oncology Dispensary

Email: 05-guz-okod@kuzdrav.ru

Chief of Thoracic Department

Russian Federation, Kemerovo

Svetlana E. Ragozhina

Regional Center of Blood

Email: ragozhina@mail.ru

Assistant of Main Physician on Medicine

Russian Federation, Kemerovo

Ilgiz A. Vafin

Regional Center of Blood

Email: stpk@kuzdrav.ru

Main Physician

Russian Federation, Kemerovo

Elizaveta L. Romanova

Kemerovo State University (KemSU)

Email: nev11@yandex.ru

Learning of The Center for Continuing Education

Russian Federation, Kemerovo

Andrey N. Glushkov

FRC CCC SB RAS (Institute of Human Ecology SB RAS)

Email: ihe@list.ru

Doctor of Medical Sciences, Deputy Director

Russian Federation, Kemerovo

References

  1. Акопов А. Современные подходы к классификации рака легкого // Врач. – 2011. – № 12. – С. 7–12. [Akopov A. Current approaches to classification of lung cancer. Vrach. 2011;(12):7-12. (In Russ.)]
  2. Одинцова И.Н., Писарева Л.Ф., Ананина О.А., Воробьев В.А. Эпидемиология рака легкого в Сибири и на Дальнем Востоке // Сибирский онкологический журнал. – 2013. – (Приложение № 2.) — С. 55–56. [Odintsova IN, Pisareva LF, Ananina OA, Vorob’ev VA. Epidemiologiya raka legkogo v Sibiri i na Dal’nem Vostoke. Siberian journal of oncology. 2013; (Suppl.2):55-56. (In Russ.)]
  3. Данилко К.В., Корытина Г.Ф., Ахмадишина Л.З., и др. Ассоциация полиморфных маркеров генов цитокинов (IL1B, IL1RN, TNFA, LTA, IL6, IL8, IL10) с развитием хронической обструктивной болезни легких // Молекулярная биология. – 2007. – Т. 41. –№ 1. – С. 26–36. [Danilko KV, Korytina GF, Akhmadishina LZ, et al. Association of cytokines genes (IL1, IL1RN, TNF, LTA, IL6, IL8, IL10) polymorphic markers with chronic obstructive pulmonary disease. Molecular Biology. 2007;41(1):26-36. (In Russ.)]
  4. Абелев Г.И., Эрайзер Т.Л. На пути к пониманию природы рака // Биохимия. – 2008. – Т. 73. – № 5. – С. 605–618. [Abelev GI, Eraiser TL. On the path to understanding the nature of cancer. Biochemistry (Moscow). 2008;73(5):605-618. (In Russ.)]
  5. Бережная М.Н. Роль клеток системы иммунитета в микроокружении опухоли. 2. Взаимодействие клеток системы иммунитета с другими компонентами микроокружения // Онкология. – 2009. – Т. 11. № 2. – С. 86–93. [Berezhnaya NM. Role of immune system cells in tumor microenvironment. II. Interaction of the immune system cells with other microenvironment components. Oncology. 2009;11(2):86-93. (In Ukrain.)]
  6. Громова А.Ю., Симбирцев А.С. Полиморфизм генов семейства IL-1 человека // Цитокины и воспаление. – 2005. – Т. 4. –№ 2. – С. 3–12. [Gromova AJu, Simbirtsev AS. Gene polymorphisms of interleukin-1 family cytokines. Cytokines and Inflammation. 2005;4(2):3-12. (In Russ.)]
  7. Гордеева Л.А., Мун С.А., Воронина Е.Н., и др. Исследование ассоциаций полиморфизма генов ферментов детоксикации ксенобиотиков и факторов среды с риском плоскоклеточного рака легкого у мужчин // Медицина в Кузбассе. – 2015. – Т. 14. – № 3. – С. 14–21. [Gordeeva LA, Mun SA, Voronina EN, et al. Research of associations of genes polymorphisms of xenobiotic-detoxifying enzymes and environmental factors with risk squamous lung cancer in male. Medicine in Kuzbass. 2015;14(3):14-21. (In Russ.)]
  8. Гордеева Л.А., Мун С.А., Воронина Е.Н., и др. Полиморфные варианты генов цитокинов (IL1B, IL1RN, TNFA и IL6) у курящих мужчин с раком легкого // Цитокины и воспаление. – 2015. – Т. 14. – № 1. – С. 50–56. [Gordeeva LA, Mun SA, Voronina EN, et al. The polymorphisms of cytokine IL1B, IL1RN, TNFA and IL6 genes in male smo kers with lung cancer. Cytokines and Inflammation. 2015;14(1):50-56. (In Russ.)]
  9. Гордеева Л.А., Оскорбина О.С., Воронина Е.Н. и др. Ассоциации полиморфизма генов цитокинов с невынашиванием беременности // Медицинская иммунология. – 2017. – Т. 19. – № 5. – С. 553–564. [Gordeeva LA, Oskorbina OS, Voronina EN, et al. Association between cytokine gene polymorphisms and recurrent miscarriage. Medical Immunology (Russia). 2017;19(5):553-564. (In Russ.)]. doi: 10.15789/1563-0625-2017-5-585-596.
  10. Гордеева Л.А., Глушкова О.А., Воронина Е.Н., и др. Ассоциации материнских полиморфизмов генов цитокинов (IL1B, IL1RN, TNF, IL4, IL6) с врожденными пороками развития у плода и новорожденного // Иммунология. – 2013. – Т. 34. – № 6. – С. 298–304. [Gordeeva LA, Glushkova OA, Voronina EN, et al. Association of maternal polymorphisms of cytokine gene (IL1B, IL1RN, TNF, IL4, IL6) with congenital malformations in fetus and newborn. Immunology. 2013; 34(6):298-304. (In Russ.)]
  11. Рубанович А.В., Хромов-Борисов Н.Н. Теоретический анализ показателей предсказательной эффективности бинарных генетических тестов // Экологическая генетика. – 2013. – Т. 11. – № 1. – С. 77–91. [Rubanovich AV, Khromov-Borisov NN. Theoretical analysis of the predictability indices of the binary genetic tests. Ecological genetics. 2013;11(1):77-91. (In Russ.)]
  12. Baune BT, Dannlowski U, Domschke K, et al. The interleukin 1 beta (IL1B) gene is associated with failure to achieve remission and impaired emotion proces sing in major depression. Biol Psychiatry. 2010;67(6): 543-9. doi: 10.1016/j.biopsych.2009.11.004.
  13. Рыдловская А.В., Симбирцев А.С. Функциональный полиморфизм гена TNFA и патология // Цитокины и воспаление. – 2005. – Т. 4. –№ 3. – С. 4–10. [Rydlovskaya AV, Simbirtsev AS. TNFA functional gene polymorphism and pathology. Cytokines and Inflammation. 2005;4(3):4-10. (In Russ.)]
  14. Назарова Е.Л., Демьянова В.Т., Шардаков В.И., и др. Ассоциации полиморфизма ряда генов врожденного иммунитета с риском развития хронических лимфопролиферативных заболеваний // Гематология и трансфузиология. – 2016. – Т. 61. – № 4. – С. 183–189. [Nazarova EL, Demiyanova VT, Shardakov BI, et al. Associations of polymorphism in several innate immunity genes with the risk of the development of chronic lymphoproliferative diseases. Hematology and Transfusiology. 2016;61(4):183-189. (In Russ.)]. doi: 10.18821/0234-5730/2016-61-4-183-189.
  15. Enewold L, Mechanic LE, Bowman ED, et al. Serum concentrations of cytokines and lung cancer survival in African Americans and Caucasians. Cancer Epidemiol Biomarkers Prev. 2009;18(1):215-22. doi: 10.1158/1055-9965.EPI-08-0705.
  16. Мукерия А.Ф., Заридзе Д.Г. Эпидемиология и профилактика рака легкого // Вестник РОНЦ им. Н.Н. Блохина РАМН. – 2010. – Т. 21. – № 3. – С. 3–13. [Mukeria AF, Zaridze DG. Lung cancer epidemiology and prevention. Journal of N.N. Blokhin Russian Cancer Research Center RAMS. 2010;21(3):3-10. (In Russ.)]
  17. Имянитов Е.Н. Молекулярная патология рака легкого: клинические аспекты // Практическая онкология. – 2003. – Т. 4. – № 3. – С. 131–139. [Imyanitov EN. Molekulyarnaya patologiya raka legkogo: klinicheskie aspekty. Prakticheskaya onkologiya. 2003;4(3):131-139. (In Russ.)]
  18. Xu J, Yin Z, Cao S, et al. Systematic Review and Meta-Analysis on the Association between IL-1B Polymorphisms and Cancer Risk. PLOS ONE. 2013;8(5):e63654. doi: 10.1371/journal.pone.0063654.
  19. Zhang Y, Changming L, Peng H, et al. IL1 Receptor Antagonist Gene IL1-RN Variable Number of Literature Review and Meta-Analysis. PLOS ONE. 2012;7(9): e46017. doi: 10.1371/journal.pone.0046017.
  20. Liu Y, Song XL, Zhang GL, et al. Lack of association between IL-6-174G>C polymorphism and lung cancer: a meta-analysis. Genet Mol Res. 2015; 14(1):163-9. doi: 10.4238/2015.
  21. Zhou W, Zhang S, Hu Y, et al. Meta-analysis of the associations between TNF-α or IL-6 gene polymorphisms and susceptibility to lung cancer. Eur J Med Res. 2015;20:28. doi: 10.1186/s40001-015-0113-9.
  22. Кучер А.Н. Ген-средовые взаимодействия как основа формирования здоровья // Экологическая генетика. – 2017. – Т. 15(4). – С. 19–32. [Kucher AN. Gene-environment interactions as the basis of health formation. Ecological genetics. 2017;15(4):19-32. doi: 10.17816/ecogen15419-32.
  23. Campa D, Zienolddiny S, Maggini V, et al. Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer. Carcinogenesis. 2004;25(2):22935.
  24. Jia W, Fei GH, Hu JG, Hu XW. A study on the effect of IL-6 gene polymorphism on the prognosis of non-small-cell lung cancer. Onco Targets Ther. 2015;8:2699-704. doi: 10.2147/OTT.S84636.
  25. Cole SW, Arevalo JM, Manu K, et al. Antagonistic pleiotropy at the human IL6 promoter confers genetic resilience to the pro-inflammatory effects of adverse social conditions in adolescence. Dev Psychol. 2011;47(4):1173-80. doi: 10.1037/a0023871.
  26. Cole SW, Arevalo JM, Takahashi R, et al. Computational identification of gene-social environment interaction at the human IL6 locus. Proc Natl Acad Sci USA. 2010;107(12):5681-6. doi: 10.1073/pnas.0911515107.
  27. Прощаев К.И., Ильницкий А.Н., Павлова Т.В., и др. Локальные и системные нейроиммуноэндокринные сдвиги под влиянием поллютантов в контексте преждевременного старения: анализ состояния проблемы // Фундаментальные исследования. – 2011. – № 6. – С. 150–153. [Prashchayeu KI, Ilnitski AN, Pavlova TV, et al. Local and systemic neyroimmunnoendokrinnye shifts under the influense of pollutants in the context of premature aging: analysis of problems. Fundamental Research. 2011;6:150-153. (In Russ.)]
  28. Зейдлиц А.А., Любарский М.С., Наров Ю.Э., Морозов В.В. Влияние регионарной лимфотропной терапии на течение воспалительного процесса при раке легкого // Бюллетень СО РАМН. – 2013. – Т. 36(6). – С. 86–91. [Zeydlits AA, Lubarsky MS, Narov YuE, Morozov VV. Impact of the regional lymphotropic therapy on inflammation at lung cancer. Bulletin SO RAMN. 2013;36(6):86-91. (In Russ.)]
  29. Ганцева Х.Х., Габитова Д.М., Афлятунова С.Ф. К патогенетическому единству в развитии хронической обструктивной болезни легких и рака легкого // Креативная хирургия и онкология. – 2010. – № 4. – С. 19–22. [Gantseva KhKh, Gabitova DM, Aflyatunova SF. To the pathogenetic unity in the development of the chronic obstructive pulmonary disease and pulmonary cancer. Creative surgery and onco logy. 2010;(4):19-22 (In Russ.)]
  30. Naugler WE, Karin M. The wolf in sheep’s clothing: the role of interleukin-6 in immunity, inflammation and cancer. Trends Mol Med. 2008;14(3):109-19. doi: 10.1016/j.molmed.2007.12.007.
  31. Ochoa CE, Mirabolfathinejad SG, Ruiz VA, et al. Interleukin 6, but not T helper 2 cytokines, promotes lung carcinogenesis. Cancer Prev Res (Phila). 2011;4(1):51-64. doi: 10.1158/1940-6207.CAPR-10-0180.
  32. Ara T, Declerck YA. Interleukin-6 in bone metastasis and cancer progression. Eur J Cancer. 2010;46(7):1223-31. doi: 10.1016/j.ejca.2010.02.026.
  33. Сибиряк С.В. Цитокины как регуляторы цито хром P450-зависимых монооксигеназ. Теоретические и прикладные аспекты // Цитокины и воспаление. – 2003. – Т. 2. – № 2. – С. 12–22. [Sibiryak SV. Cytokines as cytochrome P450 dependent monooxygenases regulators. Theoretical and applied aspects. Cytokines and Inflammation. 2003;2(2):12-22. (In Russ.)]
  34. Patel SA, Bhambra U, Charalambous MP, et al. Interleukin-6 mediated upregulation of CYP1B1 and CYP2E1 in colorectal cancer involves DNA methylation, miR27b and STAT3. Br J Cancer. 2014;111(12):2287-96. doi: 10.1038/bjc.2014.540.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. ROC-curve for the parameter duration of smoking and the test levels of sensitivity and specificity

Download (102KB)
Indexing metadata

Copyright (c) 2018 Gordeeva L.A., Mun S.A., Voronina E.N., Polenok E.G., Magatina A.D., Titov V.A., Ragozhina S.E., Vafin I.A., Romanova E.L., Glushkov A.N.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies