oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2019-18-2-70-77oncotomsk-1017Research ArticleОБЗОРЫREVIEWSПолиморфные варианты генов фолатного цикла у больных раком легкогоPolymorphism of Folate metabolism genes and risk of lung cancerhttps://orcid.org/0000-0002-1238-2427БакановаМ. Л.BakanovaM. L.

Баканова Марина Леонидовна, младший научный сотрудник лаборатории цитогенетики, Федеральный исследовательский центр угля и углехимии. SPIN-код: 3049-1531. Researcher ID (WOS): K4069-2017. Author ID (Scopus): 43661146700.

Marina L. Bakanova, Junior Researcher, Сytogenetic Laboratory. Researcher ID (WOS): K4069-2017. Author ID (Scopus): 43661146700.

18, Sovetsky pr., 650000-Kemerovo.

mari-bakano@ya.ruhttps://orcid.org/0000-0003-3485-9123МининаВ. И.MininaV. I.

Минина Варвара Ивановна, доктор биологических наук, главный научный сотрудник лаборатории цитогенетики. SPIN-код: 5153-8594. Researcher ID (WOS): E-2147-2015. Author ID (Scopus): 6603279179.

г. Кемерово, 650000, пр. Советский, 18.

Varvara I. Minina, DSc, Principal Researcher, Сytogenetic Laboratory. Researcher ID (WOS): E-2147-2015. Author ID (Scopus): 6603279179.

18, Sovetsky pr., 650000-Kemerovo.

https://orcid.org/0000-0003-0754-306XСавченкоЯ. А.SavchenkoYa. A.

Савченко Яна Александровна, кандидат биологических наук, старший научный сотрудник лаборатории цитогенетики. SPIN-код: 3783-7268. Researcher ID (WOS): K-6233-2017. Author ID (Scopus): 57016525100.

г. Кемерово, 650000, пр. Советский, 18.

Yana A. Savchenko, PhD, Senior Researcher, Сytogenetic Laboratory. Researcher ID (WOS): K-6233-2017. Author ID (Scopus): 57016525100.

18, Sovetsky pr., 650000-Kemerovo.

ГлушковА. H.GlushkovA. N.

Глушков Андрей Николаевич, доктор медицинских наук, профессор, директор. SPIN-код: 9536-8530. Researcher ID (WOS): Q-5985-2016. Author ID (Scopus): 7006323832.

г. Кемерово, 650000, пр. Советский, 18.

Andrew N. Glushkov, MD, DSc, Professor, Director of the Institute of Human Ecology. Researcher ID (WOS): Q-5985-2016. Author ID (Scopus): 7006323832.

18, Sovetsky pr., 650000-Kemerovo.

ФГБНУ «Федеральный исследовательский центр угля и углехимии Сибирского отделения Российской академии наук».РоссияFederal Research Center of Coal and Coal Chemistry of Siberian Branch of the Russian Academy of Sciences.Russian Federation2019250420191827077Copyright © Баканова М.Л., Минина В.И., Савченко Я.А., Глушков А.H., 20192019Баканова М.Л., Минина В.И., Савченко Я.А., Глушков А.H.Bakanova M.L., Minina V.I., Savchenko Y.A., Glushkov A.N.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/1017

Рак легкого (РЛ) – распространенное онкологическое заболевание и ведущая причина смертности от рака во всем мире. Особенности метаболизма фолатов в организме могут влиять на процессы метилирования и репарации ДНК и играть важную роль в процессах канцерогенеза.

Целью исследования стало обобщение имеющихся данных об ассоциации между полиморфными вариантами генов фолатного цикла (MTHFR С677Т (rs1801133), MTR A2756G (rs1805087), MTRR А66G (rs1801394)) и риском РЛ у человека.

Материал и методы

Материал и методы. Поиск исследований проводился в базе данных pubmed, elibrary.ru. В обзор включали оригинальные, рандомизированные исследования за период с 2003 по 2018 г.

Результаты

Результаты. Накоплено большое количество работ о роли гена MTHFR С677Ту больных РЛ. Данные же по полиморфным вариантам MTR A2756Gи MTRR A66Gу больных РЛ весьма ограничены. Полиморфизмы MTHFR C677Tи MTRR А66Gзначительно связаны с РЛ во многих исследованиях. Ассоциаций между геном MTR A2756Gи РЛ пока получено не было, однако в злокачественной транс-формации легкого зафиксирована значимость совместного действия MTR 2756A > Gand MTRR 66A > G. Ряд факторов, таких как национальность, курение, пол, точный диагноз, могут оказывать влияние на результаты и выводы исследований о роли генов фолатного цикла у больных РЛ.

Заключение

Заключение. Дальнейшее изучение генетических полиморфизмов MTHFR С677Т (rs1801133), MTR A2756G (rs1805087), MTRR А66G (rs1801394)с учетом ген-средовых и ген-генных взаимодействий может объяснить индивидуальные различия риска РЛ.

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer mortality worldwide. Folate metabolism plays an important role in carcinogenesis through its involvement in the process of dNamethylation and repair.

The aim of our study was to evaluate the relationship between MTHFR С677Т (rs1801133), MTR A2756G (rs1805087), MTRR А66G (rs1801394) gene polymorphisms and lung cancer risk.

Material and methods

Material and methods. Asystematic literature search was conducted in the electronic databases pubmed, elibrary.ru in the time period between 2003 and 2018.

Results

Results. The MTHFR C677Tand MTRR А66G gene polymorphisms were found to be significantly associated with lung cancer. No significant association between the MTR A2756Gpolymorphism and lung cancer risk was found. the variant alleles of MTR 2756A > Gand MTRR 66A > Gpolymorphisms may have a joint effect on lung cancer risk. anumber of factors, such as nationality, smoking, gender, and an accurate diagnosis can influence the results of studies on the role of genes involved in folate cycle in patients with lung cancer.

Conclusion

Conclusion. Future studies are needed to consider gene-gene and gene-environment interactions in lung cancer. Further investigations on MTHFR С677Т (rs1801133), MTR A2756G (rs1805087), MTRR А66G (rs1801394) polymorphisms and lung cancer susceptibility may provide a theoretical basis for lung cancer prevention.

рак легкогополиморфизм генов фолатного циклаMTHFRMTRMTRRДНКметаболизмонкогенезlung cancergenetic polymorphism of folate metabolism genes MTHFRMTRMTRRdNametabolismoncogenesisReferencesFerlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin D.M., Forman D., Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer. 2015; 136 (5): 359–386. doi: 10.1002/ijc.29210.Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin D.M., Forman D., Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer. 2015; 136 (5): 359–386. doi: 10.1002/ijc.29210.IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Tobacco smoke and involuntary smoking. IARC Monogr Eval Carcinog Risks Hum. 2004; 83: 166–167.IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Tobacco smoke and involuntary smoking. IARC Monogr Eval Carcinog Risks Hum. 2004; 83: 166–167.Brownson R.C., Alavanja M.C., Caporaso N., Berger E., Chang J.C. Family history of cancer and risk of lung cancer in lifetime non-smokers and long-term ex-smokers. Int J Epidemiol. 1997; 26: 256–263.Brownson R.C., Alavanja M.C., Caporaso N., Berger E., Chang J.C. Family history of cancer and risk of lung cancer in lifetime non-smokers and long-term ex-smokers. Int J Epidemiol. 1997; 26: 256–263.Wang Y., Broderick P., Webb E., Wu X., Vijayakrishnan J., Matakidou A., Qureshi M., Dong Q., Gu X., Chen W.V., Spitz M.R., Eisen T., Amos C.I., Houlston R.S.Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet. 2008 Dec; 40 (12): 1407–9. doi: 10.1038/ng.273.Wang Y., Broderick P., Webb E., Wu X., Vijayakrishnan J., Matakidou A., Qureshi M., Dong Q., Gu X., Chen W.V., Spitz M.R., Eisen T., Amos C.I., Houlston R.S.Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet. 2008 Dec; 40 (12): 1407–9. doi: 10.1038/ng.273.Broderick P., Wang Y., Vijayakrishnan J., Matakidou A., Spitz M.R., Eisen T., Amos C.I., Houlston R.S. Deciphering the impact of common genetic variation on lung cancer risk: a genome-wide association study. Cancer Res. 2009 Aug 15; 69 (16): 6633–41. doi: 10.1158/0008-5472.CAN-09-0680.Broderick P., Wang Y., Vijayakrishnan J., Matakidou A., Spitz M.R., Eisen T., Amos C.I., Houlston R.S. Deciphering the impact of common genetic variation on lung cancer risk: a genome-wide association study. Cancer Res. 2009 Aug 15; 69 (16): 6633–41. doi: 10.1158/0008-5472.CAN-09-0680.Hung R.J., McKay J.D., Gaborieau V., Boffetta P., Hashibe M., Zaridze D., Mukeria A., Szeszenia-Dabrowska N., Lissowska J., Rudnai P., Fabianova E., Mates D., Bencko V., Foretova L., Janout V., Chen C., Goodman G., Field J.K., Liloglou T., Xinarianos G., Cassidy A., McLaughlin J., Liu G., Narod S., Krokan H.E., Skorpen F., Elvestad M.B., Hveem K., Vatten L., Linseisen J., Clavel-Chapelon F., Vineis P., Bueno-de-Mesquita H.B., Lund E., Martinez C., Bingham S., Rasmuson T., Hainaut P., Riboli E., Ahrens W., Benhamou S., Lagiou P., Trichopoulos D., Holcátová I., Merletti F., Kjaerheim K., Agudo A., Macfarlane G., Talamini R., Simonato L., Lowry R., Conway D.I., Znaor A., Healy C., Zelenika D., Boland A., Delepine M., Foglio M., Lechner D., Matsuda F., Blanche H., Gut I., Heath S., Lathrop M., Brennan P. A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature. 2008; 452: 633–637. doi: 10.1038/nature06885.Hung R.J., McKay J.D., Gaborieau V., Boffetta P., Hashibe M., Zaridze D., Mukeria A., Szeszenia-Dabrowska N., Lissowska J., Rudnai P., Fabianova E., Mates D., Bencko V., Foretova L., Janout V., Chen C., Goodman G., Field J.K., Liloglou T., Xinarianos G., Cassidy A., McLaughlin J., Liu G., Narod S., Krokan H.E., Skorpen F., Elvestad M.B., Hveem K., Vatten L., Linseisen J., Clavel-Chapelon F., Vineis P., Bueno-de-Mesquita H.B., Lund E., Martinez C., Bingham S., Rasmuson T., Hainaut P., Riboli E., Ahrens W., Benhamou S., Lagiou P., Trichopoulos D., Holcátová I., Merletti F., Kjaerheim K., Agudo A., Macfarlane G., Talamini R., Simonato L., Lowry R., Conway D.I., Znaor A., Healy C., Zelenika D., Boland A., Delepine M., Foglio M., Lechner D., Matsuda F., Blanche H., Gut I., Heath S., Lathrop M., Brennan P. A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature. 2008; 452: 633–637. doi: 10.1038/nature06885.Wu C., Hu Z., Yu D., Huang L., Jin G., Liang J., Guo H., Tan W., Zhang M., Qian J., Lu D., Wu T., Lin D., Shen H.Genetic variants on chromosome 15q25 associated with lung cancer risk in Chinese populations. Cancer Res. 2009; 69: 5065–5072. doi: 10.1158/0008-5472.CAN-09-0081.Wu C., Hu Z., Yu D., Huang L., Jin G., Liang J., Guo H., Tan W., Zhang M., Qian J., Lu D., Wu T., Lin D., Shen H.Genetic variants on chromosome 15q25 associated with lung cancer risk in Chinese populations. Cancer Res. 2009; 69: 5065–5072. doi: 10.1158/0008-5472.CAN-09-0081.Shiraishi K., Kunitoh H., Daigo Y., Takahashi A., Goto K., Sakamoto H., Ohnami S., Shimada Y., Ashikawa K., Saito A., Watanabe S., Tsuta K., Kamatani N., Yoshida T., Nakamura Y., Yokota J., Kubo M., KohnoT. A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population. Nat. Genet. 2012; 44: 900–903. doi: 10.1038/ng.2353.Shiraishi K., Kunitoh H., Daigo Y., Takahashi A., Goto K., Sakamoto H., Ohnami S., Shimada Y., Ashikawa K., Saito A., Watanabe S., Tsuta K., Kamatani N., Yoshida T., Nakamura Y., Yokota J., Kubo M., KohnoT. A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population. Nat. Genet. 2012; 44: 900–903. doi: 10.1038/ng.2353.Yoon K.A., Park J.H., Han J., Park S., Lee G.K., Han J.Y., Zo J.I., Kim J., Lee J.E., Takahashi A., Kubo M., Nakamura Y., Lee J.S. A genomewide association study reveals susceptibility variants for non-small cell lung cancer in the Korean population. Hum Mol Genet. 2010 Dec 15; 19 (24): 4948–54. doi: 10.1093/hmg/ddq421.Yoon K.A., Park J.H., Han J., Park S., Lee G.K., Han J.Y., Zo J.I., Kim J., Lee J.E., Takahashi A., Kubo M., Nakamura Y., Lee J.S. A genomewide association study reveals susceptibility variants for non-small cell lung cancer in the Korean population. Hum Mol Genet. 2010 Dec 15; 19 (24): 4948–54. doi: 10.1093/hmg/ddq421.Wang M., Liu H., Liu Z., Yi X., Bickeboller H., Hung R.J., Brennan P., Landi M.T., Caporaso N., Christiani D.C., Doherty J.A., TRICL Research Team, Amos C.I., Wei Q. Genetic variant in DNA repair gene GTF2H4 is associated with lung cancer risk: a large-scale analysis of six published GWAS datasets in the TRICL consortium. Carcinogenesis. 2016 Sep; 37 (9): 888–896. doi: 10.1093/carcin/bgw070.Wang M., Liu H., Liu Z., Yi X., Bickeboller H., Hung R.J., Brennan P., Landi M.T., Caporaso N., Christiani D.C., Doherty J.A., TRICL Research Team, Amos C.I., Wei Q. Genetic variant in DNA repair gene GTF2H4 is associated with lung cancer risk: a large-scale analysis of six published GWAS datasets in the TRICL consortium. Carcinogenesis. 2016 Sep; 37 (9): 888–896. doi: 10.1093/carcin/bgw070.Siemianowicz K., Gminski J., Garczorz W., Slabiak N., Goss M., Machalski M., Magiera-Molendowska H. Methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms in patients with small cell and non-small cell lung cancer.Oncol Rep. 2003; 10 (5): 1341–4.Siemianowicz K., Gminski J., Garczorz W., Slabiak N., Goss M., Machalski M., Magiera-Molendowska H. Methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms in patients with small cell and non-small cell lung cancer.Oncol Rep. 2003; 10 (5): 1341–4.Shen M., Rothman N., Berndt S.I., He X., Yeager M., Welch R., Chanock S., Caporaso N., Lan Q.Polymorphisms in folate metabolic genes and lung cancer risk in Xuan Wei, China. Lung Cancer. 2005 Sep; 49 (3): 299–309. doi: 10.1016/j.lungcan.2005.04.002.Shen M., Rothman N., Berndt S.I., He X., Yeager M., Welch R., Chanock S., Caporaso N., Lan Q.Polymorphisms in folate metabolic genes and lung cancer risk in Xuan Wei, China. Lung Cancer. 2005 Sep; 49 (3): 299–309. doi: 10.1016/j.lungcan.2005.04.002.Shi Q., Zhang Z., Li G., Pillow P.C., Hernandez L.M., Spitz M.R., Wei Q. Polymorphisms of methionine synthase and methionine synthase reductase and risk of lung cancer: a case-control analysis. Pharmacogenet Genomics. 2005 Aug; 15 (8): 547–55.Shi Q., Zhang Z., Li G., Pillow P.C., Hernandez L.M., Spitz M.R., Wei Q. Polymorphisms of methionine synthase and methionine synthase reductase and risk of lung cancer: a case-control analysis. Pharmacogenet Genomics. 2005 Aug; 15 (8): 547–55.Hung R.J., Hashibe M., McKay J., Gaborieau V., SzeszeniaDabrowska N., Zaridze D., Lissowska J., Rudnai P., Fabianova E., Mates I., Foretova L., Janout V., Bencko V., Chabrier A., Moullan N., Canzian F., Hall J., Boffetta P., Brennan P. Folate-related genes and the risk of tobacco-related cancers in Central Europe.Carcinogenesis. 2007 Jun; 28 (6): 1334–1340. doi: 10.1093/carcin/bgm067.Hung R.J., Hashibe M., McKay J., Gaborieau V., SzeszeniaDabrowska N., Zaridze D., Lissowska J., Rudnai P., Fabianova E., Mates I., Foretova L., Janout V., Bencko V., Chabrier A., Moullan N., Canzian F., Hall J., Boffetta P., Brennan P. Folate-related genes and the risk of tobacco-related cancers in Central Europe.Carcinogenesis. 2007 Jun; 28 (6): 1334–1340. doi: 10.1093/carcin/bgm067.Vineis P., Veglia F., Garte S., Malaveille C., Matullo G., Dunning A., Peluso M., Airoldi L., Overvad K., Raaschou-Nielsen O., Clavel-Chapelon F., Linseisen J.P., Kaaks R., Boeing H., Trichopoulou A., Palli D., Crosignani P., Tumino R., Panico S., Bueno-De-Mesquita H.B., Peeters P.H., Lund E., Gonzalez C.A., Martinez C., Dorronsoro M., Barricarte A., Navarro C., Quiros J.R., Berglund G., Jarvholm B., Day N.E., Key T.J., Saracci R., Riboli E., Autrup H.Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers. Ann Oncol. 2007 Jul; 18 (7): 1230–42. doi: 10.1093/annonc/mdm109.Vineis P., Veglia F., Garte S., Malaveille C., Matullo G., Dunning A., Peluso M., Airoldi L., Overvad K., Raaschou-Nielsen O., Clavel-Chapelon F., Linseisen J.P., Kaaks R., Boeing H., Trichopoulou A., Palli D., Crosignani P., Tumino R., Panico S., Bueno-De-Mesquita H.B., Peeters P.H., Lund E., Gonzalez C.A., Martinez C., Dorronsoro M., Barricarte A., Navarro C., Quiros J.R., Berglund G., Jarvholm B., Day N.E., Key T.J., Saracci R., Riboli E., Autrup H.Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers. Ann Oncol. 2007 Jul; 18 (7): 1230–42. doi: 10.1093/annonc/mdm109.Cheng Z., Wang W., Dai L.L., Kang Y. MTHFR C667T polymorphism association with lung cancer risk in Henan province: a case-control study.Asian Pac J Cancer Prev. 2012; 13 (6): 2491–2494.Cheng Z., Wang W., Dai L.L., Kang Y. MTHFR C667T polymorphism association with lung cancer risk in Henan province: a case-control study.Asian Pac J Cancer Prev. 2012; 13 (6): 2491–2494.Arslan S., Karadayi S., Yildirim M.E., Ozdemir O., Akkurt I. The association between methylene-tetrahydrofolate reductase gene polymorphism and lung cancer risk.Mol Biol Rep. 2011; 38 (2): 991–6. doi: 10.1007/s11033-010-0194-z.Arslan S., Karadayi S., Yildirim M.E., Ozdemir O., Akkurt I. The association between methylene-tetrahydrofolate reductase gene polymorphism and lung cancer risk.Mol Biol Rep. 2011; 38 (2): 991–6. doi: 10.1007/s11033-010-0194-z.Kiyohara C., Horiuchi T., Takayama K., Nakanishi Y. Methylenetetrahydrofolate reductase polymorphisms and interaction with smoking and alcohol consumption in lung cancer risk: a case-control study in a Japanese population.BMC Cancer. 2011 Oct 25; 11: 459. doi: 10.1186/1471-2407-11-459.Kiyohara C., Horiuchi T., Takayama K., Nakanishi Y. Methylenetetrahydrofolate reductase polymorphisms and interaction with smoking and alcohol consumption in lung cancer risk: a case-control study in a Japanese population.BMC Cancer. 2011 Oct 25; 11: 459. doi: 10.1186/1471-2407-11-459.Aksoy-Sagirli P., Erdenay A., Kaytan-Saglam E., Kizir A. Association of Three Single Nucleotide Polymorphisms in MTR and MTRR Genes with Lung Cancer in a Turkish Population.Genet Test Mol Biomarkers. 2017; 21 (7): 428–432. doi: 10.1089/gtmb.2017.0062.Aksoy-Sagirli P., Erdenay A., Kaytan-Saglam E., Kizir A. Association of Three Single Nucleotide Polymorphisms in MTR and MTRR Genes with Lung Cancer in a Turkish Population.Genet Test Mol Biomarkers. 2017; 21 (7): 428–432. doi: 10.1089/gtmb.2017.0062.Goldbohm R.A., Voorrips L.E. Epidemiology of nutrition and lung cancer. Nestle Nutr Workshop Ser Clin Perform Programme. 2000; 4: 23–35.Goldbohm R.A., Voorrips L.E. Epidemiology of nutrition and lung cancer. Nestle Nutr Workshop Ser Clin Perform Programme. 2000; 4: 23–35.Brennan P., Fortes C., Butler J., Agudo A., Benhamou S., Darby S., Gerken M., Jökel K.H., Kreuzer M., Mallone S., Nyberg F., Pohlabeln H., Ferro G., Boffetta P. A multicenter case-control study of diet and lung cancer among non-smokers. Cancer Causes Control. 2000; 11: 49–58.Brennan P., Fortes C., Butler J., Agudo A., Benhamou S., Darby S., Gerken M., Jökel K.H., Kreuzer M., Mallone S., Nyberg F., Pohlabeln H., Ferro G., Boffetta P. A multicenter case-control study of diet and lung cancer among non-smokers. Cancer Causes Control. 2000; 11: 49–58.Männistö S., Smith-Warner S.A., Spiegelman D., Albanes D., Anderson K., van den Brandt P.A., Cerhan J.R., Colditz G., Feskanich D., Freudenheim J.L., Giovannucci E., Goldbohm R.A., Graham S., Miller A.B., Rohan T.E., Virtamo J., Willett W.C., Hunter D.J.Dietary carotenoids and risk of lung cancer in a pooled analysis of seven cohort studies. Cancer Epidemiol Biomarkers Prev. 2004; 13: 40–48.Männistö S., Smith-Warner S.A., Spiegelman D., Albanes D., Anderson K., van den Brandt P.A., Cerhan J.R., Colditz G., Feskanich D., Freudenheim J.L., Giovannucci E., Goldbohm R.A., Graham S., Miller A.B., Rohan T.E., Virtamo J., Willett W.C., Hunter D.J.Dietary carotenoids and risk of lung cancer in a pooled analysis of seven cohort studies. Cancer Epidemiol Biomarkers Prev. 2004; 13: 40–48.Darby S., Whitley E., Doll R., Key T., Silcocks P.Diet, smoking and lung cancer: a case–control study of 1000 cases and 1500 controls in South-West England. Br J Cancer. 2001; 84: 728–735. doi: 10.1054/bjoc.2000.1668.Darby S., Whitley E., Doll R., Key T., Silcocks P.Diet, smoking and lung cancer: a case–control study of 1000 cases and 1500 controls in South-West England. Br J Cancer. 2001; 84: 728–735. doi: 10.1054/bjoc.2000.1668.Wei Q., Shen H., Wang L.E., Duphorne C.M., Pillow P.C., Guo Z., Qiao Y., Spitz M.R.Association between low dietary folate intake and suboptimal cellular DNA repair capacity. Cancer Epidemiol Biomarkers Prev. 2003; 12: 963–969.Wei Q., Shen H., Wang L.E., Duphorne C.M., Pillow P.C., Guo Z., Qiao Y., Spitz M.R.Association between low dietary folate intake and suboptimal cellular DNA repair capacity. Cancer Epidemiol Biomarkers Prev. 2003; 12: 963–969.Wei Q., Cheng L., Amos C.I., Wang L.E., Guo Z., Hong W.K., Spitz M.R. Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: a molecular epidemiologic study. J Natl Cancer Inst. 2000; 92: 1764–1772.Wei Q., Cheng L., Amos C.I., Wang L.E., Guo Z., Hong W.K., Spitz M.R. Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: a molecular epidemiologic study. J Natl Cancer Inst. 2000; 92: 1764–1772.Cui L.H., Shin M.H., Kim H.N., Song H.R., Piao J.M., Kweon S.S., Choi J.S., Yun W.J., Kim Y.C., Oh I.J., Kim K.S. Methylenetetrahydrofolate reductase C677T polymorphism in patients with lung cancer in a Korean population.BMC Med Genet. 2011; 12: 28. doi: 10.1186/1471-2350-12-28.Cui L.H., Shin M.H., Kim H.N., Song H.R., Piao J.M., Kweon S.S., Choi J.S., Yun W.J., Kim Y.C., Oh I.J., Kim K.S. Methylenetetrahydrofolate reductase C677T polymorphism in patients with lung cancer in a Korean population.BMC Med Genet. 2011; 12: 28. doi: 10.1186/1471-2350-12-28.Matakidou A., El Galta R., Rudd M.F., Webb E.L., Bridle H., Eisen T., Houlston R.S. Prognostic significance of folate metabolism polymorphisms for lung cancer.Br J Cancer. 2007; 97 (2): 247–252.Matakidou A., El Galta R., Rudd M.F., Webb E.L., Bridle H., Eisen T., Houlston R.S. Prognostic significance of folate metabolism polymorphisms for lung cancer.Br J Cancer. 2007; 97 (2): 247–252.Harmon D.L., Shields D.C., Woodside J.V., McMaster D., Yarnell J.W., Young I.S., Peng K., Shane B., Evans A.E., Whitehead A.S. Methionine synthase D919G polymorphism is a significant but modest determinant of circulating homocysteineconcentrations. Genet Epidemiol.1999 Nov; 17 (4): 298–309.Harmon D.L., Shields D.C., Woodside J.V., McMaster D., Yarnell J.W., Young I.S., Peng K., Shane B., Evans A.E., Whitehead A.S. Methionine synthase D919G polymorphism is a significant but modest determinant of circulating homocysteineconcentrations. Genet Epidemiol.1999 Nov; 17 (4): 298–309.Ma J., Stampfer M.J., Christensen B., Giovannucci E., Hunter D.J., Chen J., Willett W.C., Selhub J., Hennekens C.H., Gravel R., Rozen R. A polymorphism of the methionine synthase gene: association with plasma folate, vitamin B12, homocyst(e)ine, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 1999 Sep; 8 (9): 825–829.Ma J., Stampfer M.J., Christensen B., Giovannucci E., Hunter D.J., Chen J., Willett W.C., Selhub J., Hennekens C.H., Gravel R., Rozen R. A polymorphism of the methionine synthase gene: association with plasma folate, vitamin B12, homocyst(e)ine, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 1999 Sep; 8 (9): 825–829.Дмитриева А.И., Новицкий В.В., Севостьянова Н.В., Фрей-дин М.Б., Пузырев В.П., Коломиец С.А., Черемисина О.В., Неруш Е.В., Тен И.А. Изучение полиморфизма генов GSTT1 и GSTM1 у больных раком легких. Бюллетень Сибирского отделения Российской академии медицинских наук. 2004; 24 (1): 60–62. [Dmitrieva A.I., Novitski V.V., Sevostjanova N.V., Freidin M.B., Pusyrev V.P., Kolomiets S.A., Cheremisina O.V., Nerush E.V., Ten L.A. Study of polymorphism of GSTTl and GSTMl genes in lung cancer patients. Herald of Siberian Branch of Russian Academy Medical Sciences. 2004; 24 (1): 60–62. (in Russian)].Дмитриева А.И., Новицкий В.В., Севостьянова Н.В., Фрей-дин М.Б., Пузырев В.П., Коломиец С.А., Черемисина О.В., Неруш Е.В., Тен И.А. Изучение полиморфизма генов GSTT1 и GSTM1 у больных раком легких. Бюллетень Сибирского отделения Российской академии медицинских наук. 2004; 24 (1): 60–62. [Dmitrieva A.I., Novitski V.V., Sevostjanova N.V., Freidin M.B., Pusyrev V.P., Kolomiets S.A., Cheremisina O.V., Nerush E.V., Ten L.A. Study of polymorphism of GSTTl and GSTMl genes in lung cancer patients. Herald of Siberian Branch of Russian Academy Medical Sciences. 2004; 24 (1): 60–62. (in Russian)].Баканова М.Л., Соболева О.А., Минина В.И., Савченко Я.А., Рыжкова А.В., Титов, Р.А., Титов В.А., Боярских У.А., Воронина Е.Н., Глушков А.Н. Вклад полиморфных вариантов генов фолатного цикла в цитогенетическую нестабильность клеток крови больных раком легкого. Медицинская генетика. 2017; 16 (3): 12–19. [Bakanova M.L., Soboleva O.A., Minina V.I., Savchenko Y.A., Ryzhkova A.V., Titov R.A., Titov V.A., Boyarskih U.A., Voronina E.N., Glushkov A.N. Association of polymorphism of folate metabolism genes and chromosomal aberrations in blood cells of lung cancer patients. Medical Genetics. 2017; 16 (3): 12–19. (in Russian)].Баканова М.Л., Соболева О.А., Минина В.И., Савченко Я.А., Рыжкова А.В., Титов, Р.А., Титов В.А., Боярских У.А., Воронина Е.Н., Глушков А.Н. Вклад полиморфных вариантов генов фолатного цикла в цитогенетическую нестабильность клеток крови больных раком легкого. Медицинская генетика. 2017; 16 (3): 12–19. [Bakanova M.L., Soboleva O.A., Minina V.I., Savchenko Y.A., Ryzhkova A.V., Titov R.A., Titov V.A., Boyarskih U.A., Voronina E.N., Glushkov A.N. Association of polymorphism of folate metabolism genes and chromosomal aberrations in blood cells of lung cancer patients. Medical Genetics. 2017; 16 (3): 12–19. (in Russian)].Weiner A.S., Boyarskikh U.A., Voronina E.N., Mishukova O.V., Filipenko M.L.Methylenetetrahydrofolate reductase C677T and methionine synthase A2756G polymorphisms influence on leukocyte genomic DNA methylation level. Gene. 2014 Jan 1; 533 (1): 168–72. doi: 10.1016/j.gene.2013.09.098.Weiner A.S., Boyarskikh U.A., Voronina E.N., Mishukova O.V., Filipenko M.L.Methylenetetrahydrofolate reductase C677T and methionine synthase A2756G polymorphisms influence on leukocyte genomic DNA methylation level. Gene. 2014 Jan 1; 533 (1): 168–72. doi: 10.1016/j.gene.2013.09.098.Henao O.L., Piyathilake C.J., Waterbor J.W., Funkhouser E., Johanning G.L., Heimburger D.C., Partridge E.E.Women with polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are less likely to have cervical intraepithelial neoplasia (CIN) 2 or 3. Int J Cancer. 2005; 113: 991–997. doi: 10.1002/ijc.20695.Henao O.L., Piyathilake C.J., Waterbor J.W., Funkhouser E., Johanning G.L., Heimburger D.C., Partridge E.E.Women with polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are less likely to have cervical intraepithelial neoplasia (CIN) 2 or 3. Int J Cancer. 2005; 113: 991–997. doi: 10.1002/ijc.20695.Lin J., Spitz M.R., Wang Y., Schabath M.B., Gorlov I.P., Hernandez L.M., Pillow P.C., Grossman H.B., Wu X.Polymorphisms of folate metabolic genes and susceptibility to bladder cancer: a case–control study. Carcinogenesis. 2004; 25: 1639–47. doi: 10.1093/carcin/bgh175.Lin J., Spitz M.R., Wang Y., Schabath M.B., Gorlov I.P., Hernandez L.M., Pillow P.C., Grossman H.B., Wu X.Polymorphisms of folate metabolic genes and susceptibility to bladder cancer: a case–control study. Carcinogenesis. 2004; 25: 1639–47. doi: 10.1093/carcin/bgh175.Skibola C.F., Forrest M.S., Coppedé F., Agana L., Hubbard A., Smith M.T., Bracci P.M., Holly E.A. Polymorphisms and haplotypes in folate-metabolizing genes and risk of non-Hodgkin lymphoma. Blood. 2004; 104: 2155–2162. doi: 10.1182/blood-2004-02-0557.Skibola C.F., Forrest M.S., Coppedé F., Agana L., Hubbard A., Smith M.T., Bracci P.M., Holly E.A. Polymorphisms and haplotypes in folate-metabolizing genes and risk of non-Hodgkin lymphoma. Blood. 2004; 104: 2155–2162. doi: 10.1182/blood-2004-02-0557.Olteanu H., Munson T., Banerjee R. Differences in the efficiency of reductive activation of methionine synthase and exogenous electron acceptors between the common polymorphic variants of human methionine synthase reductase. Biochemistry. 2002; 41: 13378–85.Olteanu H., Munson T., Banerjee R. Differences in the efficiency of reductive activation of methionine synthase and exogenous electron acceptors between the common polymorphic variants of human methionine synthase reductase. Biochemistry. 2002; 41: 13378–85.Jeng Y.L., Wu M.H., Huang H.B., Lin W.Y., You S.L, Chu T.Y., Chen C.J., Sun C.A.The methylenetetrahydrofolate reductase 677C-->T polymorphism and lung cancer risk in a Chinese population. Anticancer Res. 2003 Nov-Dec; 23 (6D): 5149–5152.Jeng Y.L., Wu M.H., Huang H.B., Lin W.Y., You S.L, Chu T.Y., Chen C.J., Sun C.A.The methylenetetrahydrofolate reductase 677C-->T polymorphism and lung cancer risk in a Chinese population. Anticancer Res. 2003 Nov-Dec; 23 (6D): 5149–5152.Suzuki T., Matsuo K., Hiraki A., Saito T., Sato S., Yatabe Y., Mitsudomi T., Hida T., Ueda R., Tajima K. Impact of one-carbon metabolism-related gene polymorphisms on risk of lung cancer in Japan: a case control study.Carcinogenesis. 2007; 28 (8): 1718–1725. doi: 10.1093/carcin/bgm104.Suzuki T., Matsuo K., Hiraki A., Saito T., Sato S., Yatabe Y., Mitsudomi T., Hida T., Ueda R., Tajima K. Impact of one-carbon metabolism-related gene polymorphisms on risk of lung cancer in Japan: a case control study.Carcinogenesis. 2007; 28 (8): 1718–1725. doi: 10.1093/carcin/bgm104.Liu C.S., Tsai C.W., Hsia T.C., Wang R.F., Liu C.J., Hang L.W., Chiang S.Y., Wang C.H., Tsai R.Y., Lin C.C., Bau D.T. Interaction of methylenetetrahydrofolate reductase genotype and smoking habit in Taiwanese lung cancer patients.Cancer Genom Proteom. 2009; 6 (6): 325–329.Liu C.S., Tsai C.W., Hsia T.C., Wang R.F., Liu C.J., Hang L.W., Chiang S.Y., Wang C.H., Tsai R.Y., Lin C.C., Bau D.T. Interaction of methylenetetrahydrofolate reductase genotype and smoking habit in Taiwanese lung cancer patients.Cancer Genom Proteom. 2009; 6 (6): 325–329.Ding H., Wang Y., Chen Y., Liu C., Qiu H., Kang M., Tang W. Methylenetetrahydrofolate reductase tagging polymorphisms are associated with risk of non-small cell lung cancer in eastern Chinese Han population. Oncotarget. 2017; 8 (66): 110326–110336. doi: 10.18632/oncotarget.22887.Ding H., Wang Y., Chen Y., Liu C., Qiu H., Kang M., Tang W. Methylenetetrahydrofolate reductase tagging polymorphisms are associated with risk of non-small cell lung cancer in eastern Chinese Han population. Oncotarget. 2017; 8 (66): 110326–110336. doi: 10.18632/oncotarget.22887.Heijmans B.T., Boer J.M., Suchiman H.E., Cornelisse C.J., Westendorp R.G., Kromhout D., Feskens E.J., Slagboom P.E.A common variant of the methylenetetrahydrofolate reductase gene (1p36) is associated with an increased risk of cancer. Cancer Res. 2003 Mar 15; 63 (6): 1249–1253.Heijmans B.T., Boer J.M., Suchiman H.E., Cornelisse C.J., Westendorp R.G., Kromhout D., Feskens E.J., Slagboom P.E.A common variant of the methylenetetrahydrofolate reductase gene (1p36) is associated with an increased risk of cancer. Cancer Res. 2003 Mar 15; 63 (6): 1249–1253.Liu H., Jin G., Wang H., Wu W., Liu Y., Qian J., Fan W., Ma H., Miao R., Hu Z., Sun W., Wang Y., Jin L., Wei Q., Shen H., Huang W., Lu D. Association of polymorphisms in one-carbon metabolizing genes and lung cancer risk: a case-control study in Chinese population.Lung Cancer. 2008; 61 (1): 21–29. doi: 10.1016/j.lungcan.2007.12.001.Liu H., Jin G., Wang H., Wu W., Liu Y., Qian J., Fan W., Ma H., Miao R., Hu Z., Sun W., Wang Y., Jin L., Wei Q., Shen H., Huang W., Lu D. Association of polymorphisms in one-carbon metabolizing genes and lung cancer risk: a case-control study in Chinese population.Lung Cancer. 2008; 61 (1): 21–29. doi: 10.1016/j.lungcan.2007.12.001.Yilmaz M., Kacan T., Sari I., Kilickap S. Lack of association between the MTHFRC677T polymorphism and lung cancer in a Turkish population.Asian Pac J Cancer Prev. 2014; 15 (15): 6333–6337.Yilmaz M., Kacan T., Sari I., Kilickap S. Lack of association between the MTHFRC677T polymorphism and lung cancer in a Turkish population.Asian Pac J Cancer Prev. 2014; 15 (15): 6333–6337.Al-Motassem Y., Shomaf M., Said I., Berger S., Ababneh N., Diab O., Obeidat N., Awidi A. Allele and Genotype Frequencies of the Polymorphic Methylenetetrahydrofolate Reductase and Lung Cancer in the Jordanian Population: a Case Control Study.Asian Pac J Cancer Prev. 2015; 16 (8): 3101–3109.Al-Motassem Y., Shomaf M., Said I., Berger S., Ababneh N., Diab O., Obeidat N., Awidi A. Allele and Genotype Frequencies of the Polymorphic Methylenetetrahydrofolate Reductase and Lung Cancer in the Jordanian Population: a Case Control Study.Asian Pac J Cancer Prev. 2015; 16 (8): 3101–3109.Шилова А.Н., Шкода О.С., Ломиворотов В.В., Шилова Ю.Н. Ассоциация полиморфных вариантов генов метаболизма фолиевой кислоты с риском развития рака лёгкого, рака предстательной железы, рака молочной железы и рака матки. Российский онкологический журнал. 2017; 22 (4): 203–208. [Shilova A.N., Shkoda O.S., Lomivorotov V.V., Shilova J.N. Association of the folate metabolism genes with the risk for lung, prostate, breast and uterine cancer. Russian Journal of Oncology. 2017; 22 (4): 203–208. (in Russian)]. doi: 10.18821/1028-9984-2017-22-4-203-208.Шилова А.Н., Шкода О.С., Ломиворотов В.В., Шилова Ю.Н. Ассоциация полиморфных вариантов генов метаболизма фолиевой кислоты с риском развития рака лёгкого, рака предстательной железы, рака молочной железы и рака матки. Российский онкологический журнал. 2017; 22 (4): 203–208. [Shilova A.N., Shkoda O.S., Lomivorotov V.V., Shilova J.N. Association of the folate metabolism genes with the risk for lung, prostate, breast and uterine cancer. Russian Journal of Oncology. 2017; 22 (4): 203–208. (in Russian)]. doi: 10.18821/1028-9984-2017-22-4-203-208.Durda K., Kąklewski K., Gupta S., Szydłowski M., Baszuk P., Jaworska-Bieniek K., Sukiennicki G., Kaczmarek K., Waloszczyk P., Narod S., Lubiński J., Jakubowska A. Serum folate concentration and the incidence of lung cancer.PLoSOne. 2017 May 11; 12 (5): e0177441. doi: 10.1371/journal.pone.0177441.Durda K., Kąklewski K., Gupta S., Szydłowski M., Baszuk P., Jaworska-Bieniek K., Sukiennicki G., Kaczmarek K., Waloszczyk P., Narod S., Lubiński J., Jakubowska A. Serum folate concentration and the incidence of lung cancer.PLoSOne. 2017 May 11; 12 (5): e0177441. doi: 10.1371/journal.pone.0177441.Pérez-Ramírez C., Cañadas-Garre M., Alnatsha A., Villar E., Delgado J.R., Calleja-Hernández M.Á., Faus-Dáder M.J. Impact of DNA repair, folate and glutathione gene polymorphisms on risk of non small cell lung cancer.Pathol Res Pract. 2018 Jan; 214 (1): 44–52. doi: 10.1016/j.prp.2017.11.015.Pérez-Ramírez C., Cañadas-Garre M., Alnatsha A., Villar E., Delgado J.R., Calleja-Hernández M.Á., Faus-Dáder M.J. Impact of DNA repair, folate and glutathione gene polymorphisms on risk of non small cell lung cancer.Pathol Res Pract. 2018 Jan; 214 (1): 44–52. doi: 10.1016/j.prp.2017.11.015.Mao R., Fan Y., Jin Y., Bai J., Fu S. Methylenetetrahydrofolate reductase gene polymorphisms and lung cancer: a meta-analysis.J Hum Genet. 2008; 53 (4): 340–348. doi: 10.1007/s10038-008-0262-6.Mao R., Fan Y., Jin Y., Bai J., Fu S. Methylenetetrahydrofolate reductase gene polymorphisms and lung cancer: a meta-analysis.J Hum Genet. 2008; 53 (4): 340–348. doi: 10.1007/s10038-008-0262-6.Boccia S., Boffetta P., Brennan P., Ricciardi G., Gianfagna F., Matsuo K., van Duijn C.M., Hung R.J. Meta-analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and risk of head and neck and lung cancer.Cancer Lett. 2009 Jan 8; 273 (1): 55–61. doi: 10.1016/j.canlet.2008.07.026.Boccia S., Boffetta P., Brennan P., Ricciardi G., Gianfagna F., Matsuo K., van Duijn C.M., Hung R.J. Meta-analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and risk of head and neck and lung cancer.Cancer Lett. 2009 Jan 8; 273 (1): 55–61. doi: 10.1016/j.canlet.2008.07.026.Hou X.H., Huang Y.M., Mi Y.Y. Methylenetetrahydrofolate reductase gene C677T polymorphism and lung cancer: an updated metaanalysis.Asian Pac J Cancer Prev. 2012; 13 (5): 2025–2029.Hou X.H., Huang Y.M., Mi Y.Y. Methylenetetrahydrofolate reductase gene C677T polymorphism and lung cancer: an updated metaanalysis.Asian Pac J Cancer Prev. 2012; 13 (5): 2025–2029.Zhang Y., Chen G.Q., Ji Y., Huang B., Shen W.S., Deng L.C., Xi L., Cao X.M. Quantitative assessment of the effect of MTHFR polymorphisms on the risk of lung carcinoma.Mol Biol Rep. 2012 May; 39 (5): 6203–6211. doi: 10.1007/s11033-011-1439-1.Zhang Y., Chen G.Q., Ji Y., Huang B., Shen W.S., Deng L.C., Xi L., Cao X.M. Quantitative assessment of the effect of MTHFR polymorphisms on the risk of lung carcinoma.Mol Biol Rep. 2012 May; 39 (5): 6203–6211. doi: 10.1007/s11033-011-1439-1.Liu Z.B., Wang L.P., Shu J., Jin C., Lou Z.X. Methylenetetrahydrofolate reductase 677TT genotype might be associated with an increased lung cancer risk in Asians.Gene. 2013; 515 (1): 214–219. doi: 10.1016/j.gene.2012.11.036.Liu Z.B., Wang L.P., Shu J., Jin C., Lou Z.X. Methylenetetrahydrofolate reductase 677TT genotype might be associated with an increased lung cancer risk in Asians.Gene. 2013; 515 (1): 214–219. doi: 10.1016/j.gene.2012.11.036.Liu N.B., Li J., Qi J.F., Zhang Z.Z., Wu X., Zhang H. Methylenetetrahydrofolate reductase 677TT genotype may be associated with an increased lung cancer risk in North China: an updated meta-analysis.Med Sci Monit. 2014 Dec 29; 20: 2817–23. doi: 10.12659/MSM.892050.Liu N.B., Li J., Qi J.F., Zhang Z.Z., Wu X., Zhang H. Methylenetetrahydrofolate reductase 677TT genotype may be associated with an increased lung cancer risk in North China: an updated meta-analysis.Med Sci Monit. 2014 Dec 29; 20: 2817–23. doi: 10.12659/MSM.892050.Rai V. Folate pathway gene MTHFR C677T polymorphism and risk of lung cancer in Asian populations.Asian Pac J Cancer Prev. 2014; 15 (21): 9259–9264.Rai V. Folate pathway gene MTHFR C677T polymorphism and risk of lung cancer in Asian populations.Asian Pac J Cancer Prev. 2014; 15 (21): 9259–9264.Yang Y., Yang L.J., Deng M.Z., Luo Y.Y., Wu S., Xiong L., Wang D., Liu Y., Liu H. MTHFR C677T and A1298C polymorphisms and risk of lung cancer: a comprehensive evaluation.Genet Mol Res. 2016; 15 (2). doi: 10.4238/gmr.15027615.Yang Y., Yang L.J., Deng M.Z., Luo Y.Y., Wu S., Xiong L., Wang D., Liu Y., Liu H. MTHFR C677T and A1298C polymorphisms and risk of lung cancer: a comprehensive evaluation.Genet Mol Res. 2016; 15 (2). doi: 10.4238/gmr.15027615.Xie S.Z., Liu Z.Z., Yu J.H., Liu L., Wang W., Xie D.L., Qin J.B. Association between the MTHFR C677T polymorphism and risk of cancer: evidence from 446 case-control studies.Tumour Biol. 2015 Nov; 36 (11): 8953–72. doi: 10.1007/s13277-015-3648-z.Xie S.Z., Liu Z.Z., Yu J.H., Liu L., Wang W., Xie D.L., Qin J.B. Association between the MTHFR C677T polymorphism and risk of cancer: evidence from 446 case-control studies.Tumour Biol. 2015 Nov; 36 (11): 8953–72. doi: 10.1007/s13277-015-3648-z.Wang X., Yue K., Hao L. Meta-analysis of methylenetetrahydrofolate reductase polymorphism and lung cancer risk in Chinese.Int J Clin Exp Med. 2015 Jan 15; 8 (1): 1521–1525.Wang X., Yue K., Hao L. Meta-analysis of methylenetetrahydrofolate reductase polymorphism and lung cancer risk in Chinese.Int J Clin Exp Med. 2015 Jan 15; 8 (1): 1521–1525.Zhang X.D., Li Y.T., Yang S.Y., Li W. Meta-analysis on MTHFR polymorphism and lung cancer susceptibility in East Asian populations. Biomed Rep. 2013; 1 (3): 440–446. doi: 10.3892/br.2013.68.Zhang X.D., Li Y.T., Yang S.Y., Li W. Meta-analysis on MTHFR polymorphism and lung cancer susceptibility in East Asian populations. Biomed Rep. 2013; 1 (3): 440–446. doi: 10.3892/br.2013.68.Shi Q., Zhang Z., Li G., Pillow P.C., Hernandez L.M., Spitz M.R., Wei Q. Sex differences in risk of lung cancer associated with methylenetetrahydrofolate reductasepolymorphisms. Cancer Epidemiol Biomarkers Prev. 2005; 14 (6): 1477–84. doi: 10.1158/1055-9965.EPI-04-0905.Shi Q., Zhang Z., Li G., Pillow P.C., Hernandez L.M., Spitz M.R., Wei Q. Sex differences in risk of lung cancer associated with methylenetetrahydrofolate reductasepolymorphisms. Cancer Epidemiol Biomarkers Prev. 2005; 14 (6): 1477–84. doi: 10.1158/1055-9965.EPI-04-0905.Piskac-Collier A.L., Monroy C., Lopez M.S., Cortes A., Etzel C.J., Greisinger A.J., Spitz M.R., El-Zein R.A. Variants in folate pathway genes as modulators of genetic instability and lung cancer risk. Genes Chromosomes Cancer. 2011 Jan; 50 (1): 1–12. doi: 10.1002/gcc.20826.Piskac-Collier A.L., Monroy C., Lopez M.S., Cortes A., Etzel C.J., Greisinger A.J., Spitz M.R., El-Zein R.A. Variants in folate pathway genes as modulators of genetic instability and lung cancer risk. Genes Chromosomes Cancer. 2011 Jan; 50 (1): 1–12. doi: 10.1002/gcc.20826.

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