非酒精性脂肪性肝病与结直肠肿瘤的相关性

黄翔谦; 闫晓檬; 张明达; 吴静; 陈建宏

doi:10.3969/j.issn.1001-5256.2021.12.045

非酒精性脂肪性肝病与结直肠肿瘤的相关性

DOI: 10.3969/j.issn.1001-5256.2021.12.045

黄翔谦¹,
闫晓檬¹,
张明达¹,
吴静^2, ,,
陈建宏^1, ,

1.
首都医科大学附属北京世纪坛医院消化内科，北京 100038
2.
首都医科大学附属北京友谊医院消化内科国家消化系统疾病临床医学研究中心，北京市消化疾病中心, 消化疾病癌前病变北京市重点实验室，北京 100050

基金项目:

国家自然科学基金 (81900505);

北京市医院管理中心“青苗”计划资助项目 (QML20200702);

北京世纪坛医院青年基金 (2018-q09)

详细信息

通信作者:
吴静，wujing36@163.com

陈建宏，chenjianhong829@126.com

中图分类号: R575.5
计量
- 文章访问数: 548
- HTML全文浏览量: 110
- PDF下载量: 51
- 被引次数: 0
出版历程
- 收稿日期: 2021-04-22
- 录用日期: 2021-06-21
- 出版日期: 2021-12-20

Association between nonalcoholic fatty liver disease and colorectal neoplasms

1.
Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
2.
Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University; National Clinical Research Center for Digestive Diseases; Beijing Digestive Disease Center; Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing 100050, China

Research funding:

National Natural Science Foundation of China (81900505);

Beijing Municipal Administration of Hospitals' Youth Program (QML20200702);

Youth Fund of Beijing Shijitan Hospital (2018-q09)

摘要

摘要: 非酒精性脂肪性肝病(NAFLD)被认为是代谢综合征的肝脏表现，与结直肠肿瘤的发生发展密切相关。简述了NAFLD和结直肠腺瘤、结直肠癌的相关性及可能机制，认为NAFLD促进结直肠腺瘤、结直肠癌的发生并影响其预后，胰岛素抵抗、脂肪细胞因子、炎症反应、肠道菌群、免疫等多种因素可能参与其中。
- 非酒精性脂肪性肝病 /
- 结直肠肿瘤 /
- 病理过程
Abstract: Nonalcoholic fatty liver disease (NAFLD) is considered the liver manifestation of metabolic syndrome and is closely associated with the development and progression of colorectal neoplasms. This article reviews the association of NAFLD with colorectal adenoma (CRA) and colorectal cancer (CRC) and possible mechanism, and it is believed that NAFLD promotes the development of CRA and CRC and affects their prognosis, and various factors, such as insulin resistance, adipocytokine, inflammatory response, intestinal flora, and immunity, may be involved in this process.
- Non-alcoholic Fatty Liver Disease /
- Colorectal Neoplasms /
- Pathologic Processes

HTML全文

参考文献(56)

[1]	YOUNOSSI ZM, KOENIG AB, ABDELATIF D, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes[J]. Hepatology, 2016, 64(1): 73-84. DOI: 10.1002/hep.28431.
[2]	National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association, Fatty Liver Expert Committee, Chinese Medical Doctor Association. Guidelines of prevention and treatment for nonalcoholic fatty liver disease: A 2018 update[J]. J Clin Hepatol, 2018, 34(5): 947-957. DOI: 10.3969/j.issn.1001-5256.2018.05.007.
[3]	BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424. DOI: 10.3322/caac.21492.
[4]	ZHENG RS, SUN KX, ZHANG SW, et al. Report of cancer epidemiology in China, 2015[J]. China Cancer, 2019, 41(1): 19-28. DOI: 10.3760/cma.j.issn.0253-3766.2019.01.008. 郑荣寿, 孙可欣, 张思维, 等. 2015年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2019, 41(1): 19-28. DOI: 10.3760/cma.j.issn.0253-3766.2019.01.008.
[5]	LU ZY, SHAO Z, LI YL, et al. Prevalence of and risk factors for non-alcoholic fatty liver disease in a Chinese population: An 8-year follow-up study[J]. World J Gastroenterol, 2016, 22(13): 3663-3669. DOI: 10.3748/wjg.v22.i13.3663.
[6]	QIAO DW, LI YF, XIAO Y, et al. Research progress of Scutellaria barbata against colorectal cancer and its metastasis mechanism[J]. Chin J Clin Pharmacol Ther, 2019, 24(3): 332-336. DOI: 10.12092/j.issn.1009-2501.2019.03.016. 乔大伟, 李玉芳, 肖云, 等. 半枝莲抗结直肠癌及其转移机制研究进展[J]. 中国临床药理学与治疗学, 2019, 24(3): 332-336. DOI: 10.12092/j.issn.1009-2501.2019.03.016.
[7]	JIMBA S, NAKAGAMI T, TAKAHASHI M, et al. Prevalence of non-alcoholic fatty liver disease and its association with impaired glucose metabolism in Japanese adults[J]. Diabet Med, 2005, 22(9): 1141-1145. DOI: 10.1111/j.1464-5491.2005.01582.x.
[8]	KYRGIOU M, KALLIALA I, MARKOZANNES G, et al. Adiposity and cancer at major anatomical sites: Umbrella review of the literature[J]. BMJ, 2017, 356: j477. DOI: 10.1136/bmj.j477.
[9]	HWANG ST, CHO YK, PARK JH, et al. Relationship of non-alcoholic fatty liver disease to colorectal adenomatous polyps[J]. J Gastroenterol Hepatol, 2010, 25(3): 562-567. DOI: 10.1111/j.1440-1746.2009.06117.x.
[10]	BLACKETT JW, VERNA EC, LEBWOHL B. Increased prevalence of colorectal adenomas in patients with nonalcoholic fatty liver disease: A cross-sectional study[J]. Dig Dis, 2020, 38(3): 222-230. DOI: 10.1159/000502684.
[11]	WONG VW, WONG GL, TSANG SW, et al. High prevalence of colorectal neoplasm in patients with non-alcoholic steatohepatitis[J]. Gut, 2011, 60(6): 829-836. DOI: 10.1136/gut.2011.237974.
[12]	BHATT BD, LUKOSE T, SIEGEL AB, et al. Increased risk of colorectal polyps in patients with non-alcoholic fatty liver disease undergoing liver transplant evaluation[J]. J Gastrointest Oncol, 2015, 6(5): 459-468. DOI: 10.3978/j.issn.2078-6891.2015.050.
[13]	TOUZIN NT, BUSH KN, WILLIAMS CD, et al. Prevalence of colonic adenomas in patients with nonalcoholic fatty liver disease[J]. Therap Adv Gastroenterol, 2011, 4(3): 169-176. DOI: 10.1177/1756283X11402118.
[14]	ZE EY, KIM BJ, JUN DH, et al. The fatty liver index: A simple and accurate predictor of colorectal adenoma in an average-risk population[J]. Dis Colon Rectum, 2018, 61(1): 36-42. DOI: 10.1097/DCR.0000000000000973.
[15]	CHEN QF, ZHOU XD, SUN YJ, et al. Sex-influenced association of non-alcoholic fatty liver disease with colorectal adenomatous and hyperplastic polyps[J]. World J Gastroenterol, 2017, 23(28): 5206-5215. DOI: 10.3748/wjg.v23.i28.5206.
[16]	KIM NH, JUNG YS, PARK JH, et al. Impact of nonalcoholic fatty liver disease on the risk of metachronous colorectal neoplasia after polypectomy[J]. Korean J Intern Med, 2021, 36(3): 557-567. DOI: 10.3904/kjim.2019.360.
[17]	KIM GA, LEE HC, CHOE J, et al. Association between non-alcoholic fatty liver disease and cancer incidence rate[J]. J Hepatol, 2017. DOI: 10.1016/j.jhep.2017.09.012.[Online ahead of print]
[18]	CHOI YJ, LEE DH, HAN KD. Association between high fatty liver index and development of colorectal cancer: A nationwide cohort study with 21, 592, 374 Korean[J]. Korean J Intern Med, 2020, 35(6): 1354-1363. DOI: 10.3904/kjim.2018.022.
[19]	LEE YI, LIM YS, PARK HS. Colorectal neoplasms in relation to non-alcoholic fatty liver disease in Korean women: A retrospective cohort study[J]. J Gastroenterol Hepatol, 2012, 27(1): 91-95. DOI: 10.1111/j.1440-1746.2011.06816.x.
[20]	CHUAN LX, CHANG J, ZHAO JH, et al. Association between nonalcoholic fatty liver disease and colorectal adenomatous polyps[J]. J Clin Hepatol, 2020, 36(6): 1299-1303. DOI: 10.3969/j.issn.1001-5256.2020.06.022. 钏莉雪, 常江, 赵锦涵, 等. 非酒精性脂肪性肝病与结直肠腺瘤性息肉的相关性分析[J]. 临床肝胆病杂志, 2020, 36(6): 1299-1303. DOI: 10.3969/j.issn.1001-5256.2020.06.022.
[21]	LV Y, ZHANG HJ. Effect of non-alcoholic fatty liver disease on the risk of synchronous liver metastasis: Analysis of 451 consecutive patients of newly diagnosed colorectal cancer[J]. Front Oncol, 2020, 10: 251. DOI: 10.3389/fonc.2020.00251.
[22]	LV Y, PATEL N, ZHANG HJ. The progress of non-alcoholic fatty liver disease as the risk of liver metastasis in colorectal cancer[J]. Expert Rev Gastroenterol Hepatol, 2019, 13(12): 1169-1180. DOI: 10.1080/17474124.2019.1697231.
[23]	OHASHI K, WANG Z, YANG YM, et al. NOD-like receptor C4 inflammasome regulates the growth of colon cancer liver metastasis in NAFLD[J]. Hepatology, 2019, 70(5): 1582-1599. DOI: 10.1002/hep.30693.
[24]	MOLLA NW, HASSANAIN MM, FADEL Z, et al. Effect of non-alcoholic liver disease on recurrence rate and liver regeneration after liver resection for colorectal liver metastases[J]. Curr Oncol, 2017, 24(3): e233-e243. DOI: 10.3747/co.24.3133.
[25]	WU K, ZHAI MZ, WELTZIEN EK, et al. Non- alcoholic fatty liver disease and colorectal cancer survival[J]. Cancer Causes Control, 2019, 30(2): 165-168. DOI: 10.1007/s10552-018-1095-z.
[26]	CHEN ZF, DONG XL, HUANG QK, et al. The combined effect of non-alcoholic fatty liver disease and metabolic syndrome on colorectal carcinoma mortality: A retrospective in Chinese females[J]. World J Surg Oncol, 2018, 16(1): 163. DOI: 10.1186/s12957-018-1461-z.
[27]	FARAHANI H, MAHMOUDI T, ASADI A, et al. Insulin resistance and colorectal cancer risk: The role of elevated plasma resistin levels[J]. J Gastrointest Cancer, 2020, 51(2): 478-483. DOI: 10.1007/s12029-019-00260-7.
[28]	UNGER RH, SCHERER PE. Gluttony, sloth and the metabolic syndrome: A roadmap to lipotoxicity[J]. Trends Endocrinol Metab, 2010, 21(6): 345-352. DOI: 10.1016/j.tem.2010.01.009.
[29]	TARANTINO G, SAVASTANO S, COLAO A. Hepatic steatosis, low-grade chronic inflammation and hormone/growth factor/adipokine imbalance[J]. World J Gastroenterol, 2010, 16(38): 4773-4783. DOI: 10.3748/wjg.v16.i38.4773.
[30]	NAKATSU G, LI X, ZHOU H, et al. Gut mucosal microbiome across stages of colorectal carcinogenesis[J]. Nat Commun, 2015, 6: 8727. DOI: 10.1038/ncomms9727.
[31]	RAU M, SCHILLING AK, MEERTENS J, et al. Progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis is marked by a higher frequency of Th17 cells in the liver and an increased Th17/resting regulatory T cell ratio in peripheral blood and in the liver[J]. J Immunol, 2016, 196(1): 97-105. DOI: 10.4049/jimmunol.1501175.
[32]	YAMAMOTO K, TAKAHARA K, OYADOMARI S, et al. Induction of liver steatosis and lipid droplet formation in ATF6alpha-knockout mice burdened with pharmacological endoplasmic reticulum stress[J]. Mol Biol Cell, 2010, 21(17): 2975-2986. DOI: 10.1091/mbc.E09-02-0133.
[33]	MCKEOWN-EYSSEN G. Epidemiology of colorectal cancer revisited: Are serum triglycerides and/or plasma glucose associated with risk?[J]. Cancer Epidemiol Biomarkers Prev, 1994, 3(8): 687-695.
[34]	PAREKH N, OKADA T, LU-YAO GL. Obesity, insulin resistance, and cancer prognosis: Implications for practice for providing care among cancer survivors[J]. J Am Diet Assoc, 2009, 109(8): 1346-1353. DOI: 10.1016/j.jada.2009.05.001.
[35]	POLOZ Y, STAMBOLIC V. Obesity and cancer, a case for insulin signaling[J]. Cell Death Dis, 2015, 6: e2037. DOI: 10.1038/cddis.2015.381.
[36]	COMSTOCK SS, LEWIS MM, PATHAK DR, et al. Cross-sectional analysis of obesity and serum analytes in males identifies sRAGE as a novel biomarker inversely associated with diverticulosis[J]. PLoS One, 2014, 9(4): e95232. DOI: 10.1371/journal.pone.0095232.
[37]	BARKER N, van ES JH, KUIPERS J, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5[J]. Nature, 2007, 449(7165): 1003-1007. DOI: 10.1038/nature06196.
[38]	TARANTINO G, CONCA P, PASANISI F, et al. Could inflammatory markers help diagnose nonalcoholic steatohepatitis?[J]. Eur J Gastroenterol Hepatol, 2009, 21(5): 504-511. DOI: 10.1097/MEG.0b013e3283229b40.
[39]	LANTHIER N, MOLENDI-COSTE O, CANI PD, et al. Kupffer cell depletion prevents but has no therapeutic effect on metabolic and inflammatory changes induced by a high-fat diet[J]. FASEB J, 2011, 25(12): 4301-4311. DOI: 10.1096/fj.11-189472.
[40]	BATES RC, MERCURIO AM. Tumor necrosis factor-alpha stimulates the epithelial-to-mesenchymal transition of human colonic organoids[J]. Mol Biol Cell, 2003, 14(5): 1790-1800. DOI: 10.1091/mbc.e02-09-0583.
[41]	POMMIER A, ANAPARTHY N, MEMOS N, et al. Unresolved endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases[J]. Science, 2018, 360(6394): eaao4908. DOI: 10.1126/science.aao4908.
[42]	LE ROY T, LLOPIS M, LEPAGE P, et al. Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice[J]. Gut, 2013, 62(12): 1787-1794. DOI: 10.1136/gutjnl-2012-303816.
[43]	CLAESSON MJ, CUSACK S, O'SULLIVAN O, et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly[J]. Proc Natl Acad Sci U S A, 2011, 108 Suppl 1: 4586-4591. DOI: 10.1073/pnas.1000097107.
[44]	RAMAN M, AHMED I, GILLEVET PM, et al. Fecal microbiome and volatile organic compound metabolome in obese humans with nonalcoholic fatty liver disease[J]. Clin Gastroenterol Hepatol, 2013, 11(7): 868-875. e1-3. DOI: 10.1016/j.cgh.2013.02.015.
[45]	BÄCKHED F, DING H, WANG T, et al. The gut microbiota as an environmental factor that regulates fat storage[J]. Proc Natl Acad Sci U S A, 2004, 101(44): 15718-15723. DOI: 10.1073/pnas.0407076101.
[46]	TJALSMA H, BOLEIJ A, MARCHESI JR, et al. A bacterial driver-passenger model for colorectal cancer: Beyond the usual suspects[J]. Nat Rev Microbiol, 2012, 10(8): 575-582. DOI: 10.1038/nrmicro2819.
[47]	TOPRAK NU, YAGCI A, GULLUOGLU BM, et al. A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer[J]. Clin Microbiol Infect, 2006, 12(8): 782-786. DOI: 10.1111/j.1469-0691.2006.01494.x.
[48]	HUYCKE MM, ABRAMS V, MOORE DR. Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA[J]. Carcinogenesis, 2002, 23(3): 529-536. DOI: 10.1093/carcin/23.3.529.
[49]	MA C, KESARWALA AH, EGGERT T, et al. NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepato-carcinogenesis[J]. Nature, 2016, 531(7593): 253-257. DOI: 10.1038/nature16969.
[50]	WANG R, LI D, QI WJ, et al. HIF-1 α Expression and clinical significance of Th17/Treg in peripheral blood of patients with nonalcoholic fatty liver disease[J]. Chin J Med Offic, 2019, 47(1): 64-65. DOI: 10.16680/j.1671-3826.2019.01.22. 王锐, 李多, 齐维娟, 等. HIF-1α及Th17/Treg在非酒精性脂肪性肝病患者外周血中表达及临床意义[J]. 临床军医杂志, 2019, 47(1): 64-65. DOI: 10.16680/j.1671-3826.2019.01.22.
[51]	KUWAHARA T, HAZAMA S, SUZUKI N, et al. Correction: Intratumoural-infiltrating CD4⁺ and FOXP3⁺ T cells as strong positive predictive markers for the prognosis of resectable colorectal cancer[J]. Br J Cancer, 2019, 121(11): 983-984. DOI: 10.1038/s41416-019-0605-4.
[52]	CHAE WJ, GIBSON TF, ZELTERMAN D, et al. Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis[J]. Proc Natl Acad Sci U S A, 2010, 107(12): 5540-5544. DOI: 10.1073/pnas.0912675107.
[53]	NUMASAKI M, FUKUSHI J, ONO M, et al. Interleukin-17 promotes angiogenesis and tumor growth[J]. Blood, 2003, 101(7): 2620-2627. DOI: 10.1182/blood-2002-05-1461.
[54]	CHAKRABORTY D, WANG J. Nonalcoholic fatty liver disease and colorectal cancer: Correlation and missing links[J]. Life Sci, 2020, 262: 118507. DOI: 10.1016/j.lfs.2020.118507.
[55]	KIM JK, KANG KA, PIAO MJ, et al. Endoplasmic reticulum stress induces 5-fluorouracil resistance in human colon cancer cells[J]. Environ Toxicol Pharmacol, 2016, 44: 128-133. DOI: 10.1016/j.etap.2016.05.005.
[56]	POMMIER A, ANAPARTHY N, MEMOS N, et al. Unresolved endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases[J]. Science, 2018, 360(6394): eaa04908. DOI: 10.1126/science.aao4908.