二甲双胍与结直肠腺瘤患病风险相关性的荟萃分析

doi:10.3877/cma.j.issn.2095-3224.2019.01.011

目的

探索糖尿病患者服用二甲双胍是否可降低患结肠直肠腺瘤的风险。

方法

从PubMed、Elsevier-ScienceDirect、万方、维普数据库中检索建库以来至2017年7月所有关于2型糖尿病患者使用二甲双胍与患结直肠腺瘤风险相关性的研究。按照纳入及排除标准选择入选。

结果

共计纳入9项研究，其中实验组4 256例，对照组17 206例，结果显示，服用二甲双胍者较未服用二甲双胍者患结直肠腺瘤风险降低（OR=0.83，95%CI：0.72~0.95；P=0.008），差异具有统计学意义。

结论

二甲双胍的使用可能与结肠直肠腺瘤的风险降低有关。

关键词: 腺瘤, 结直肠肿瘤, 二甲双胍, Meta分析

Objective

To explore whether the use of metformin can reduce the risk of colorectal adenoma in diabetic patients.

Methods

We conducted a systematic literature search on PubMed, Elsevier-Science Direct, Wanfang, Wipu database to retrieve the database about correlation between the use of metformin in patients with type 2 diabetes and the risk of colorectal adenoma since the construction to July 2017.

Results

Finally, nine articles were included in our study, including experimental group 4256 cases, the control group 17 206 cases, The results showed that the risk of colorectal adenoma in patients taking metformin was significantly lower than those not taking metformin (OR=0.83, 95%CI 0.72~0.95, P=0.008), the difference was statistically significant.

Conclusion

The use of metformin may be associated with a reduced risk of colorectal adenoma.

Key words: Adenoma, Colorectal neoplasms, Metformin, Meta analysis

表1 纳入文献的基本特征及评分

纳入文献	国家	研究时限	研究类型	实验组	对照组	NOS评分
James 2008^[14]	美国	2000~2008	病例对照	1710	4074	7
James 2008^[14]	美国	2000~2008	病例对照	1302	12 229	7
James 2008^[14]	美国	2000~2008	病例对照	230	2499	7
Eddi 2012^[15]	美国	2006~2008	病例对照	118	926	7
Lee 2012^[16]	韩国	1998~2008	队列研究	147	184	8
Wong 2012^[17]	美国	1998~2007	病例对照	418	651	7
Cho 2014^[18]	韩国	2001~2013	队列研究	1051	2643	7
Kim 2015^[19]	韩国	2002~2012	队列研究	231	142	8
Jain 2016^[20]	美国	未提及	队列研究	334	126	6

表1 纳入文献的基本特征及评分

纳入文献	国家	研究时限	研究类型	实验组	对照组	NOS评分
James 2008^[14]	美国	2000~2008	病例对照	1710	4074	7
James 2008^[14]	美国	2000~2008	病例对照	1302	12 229	7
James 2008^[14]	美国	2000~2008	病例对照	230	2499	7
Eddi 2012^[15]	美国	2006~2008	病例对照	118	926	7
Lee 2012^[16]	韩国	1998~2008	队列研究	147	184	8
Wong 2012^[17]	美国	1998~2007	病例对照	418	651	7
Cho 2014^[18]	韩国	2001~2013	队列研究	1051	2643	7
Kim 2015^[19]	韩国	2002~2012	队列研究	231	142	8
Jain 2016^[20]	美国	未提及	队列研究	334	126	6

图1 文献筛选流程及结果

图2 结直肠腺瘤在服用、未服用二甲双胍者中患病人数比较的Meta分析结果

图3 Meta分析结果的漏斗图

[1]	Lin OS, Kozarek RA, Cha JM. Impact of sigmoidoscopy and colonoscopy on colorectal cancer incidence and mortality: an evidence-based review of published prospective and retrospective studies [J]. Intest Res, 2014, 12(4): 268-274.
[2]	Ng SC, Wong SH. Colorectal cancer screening in Asia [J]. Br Med Bull, 2013, 105: 29-42.
[3]	Ferlay J, Shin HR, Bray F,et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 [J]. Int J Cancer, 2010, 127: 2893-2917.
[4]	宋彩霞，马强. 二甲双胍抑制结直肠肿瘤的相关机制研究进展[J]. 中国肿瘤临床, 2016, 43(22): 1012-1016.
[5]	Zhu N, Zhang Y, Gong YI, et al. Metformin and lung cancer risk of patients with type 2 diabetes mellitus: A meta-analysis [J]. Biomed Rep, 2015, 3(2): 235-241.
[6]	Tseng CH.Response to letter to the editor on comments on use of metformin and risk of kidney cancer in patients with type 2 diabetes [J]. Eur J Cancer, 2016, 52(3): 19-25.
[7]	Kourelis TV, Siegel RD. Metformin and cancer: new applications for an old drug [J]. Med Oncol, 2012, 29(2): 1314-1327.
[8]	Nangia-Makker P, Yu Y, Vasudevan A, et al. Metformin: a potential therapeutic agent for recurrent colon cancer [J]. PLoS One, 2014, 9(1): e84369.
[9]	Mei ZB, Zhang ZJ, Liu CY,et al. Survival benefits of metformin for colorectal cancer patients with diabetes: a systematic review and meta-analysis [J]. PLoS One, 2014, 9(7): e91818.
[10]	He XK, Su TT, Si JM, et al. Metformin Is Associated With Slightly Reduced Risk of Colorectal Cancer and Moderate Survival Benefits in Diabetes Mellitus: A Meta-Analysis [J]. Medicine (Baltimore), 2016, 95(7): e2749.
[11]	Liu F, Yan L, Wang Z, et al. Metformin therapy and risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients: A systematic review and meta-analysis [J].Oncotarget, 2017, 8 (9): 16017-16026.
[12]	Nie Z, Zhu H, Gu M. Reduced colorectal cancer incidence in type 2 diabetic patients treated with metformin: a meta-analysis [J]. Pharm Biol, 2016, 54(11): 2636-2642.
[13]	Rokkas T, Portincasa P. Colon neoplasia in patients with type 2 diabetes on metformin: A meta-analysis [J]. Eur J Intern Med, 2016, 33: 60-66.
[14]	James D, Angela M, Ninah S, et al. Thiazolidinedione Therapy Is Not Associated With Increased Colonic Neoplasia Risk in Patients With Diabetes Mellitus [J]. Gastroenterology, 2008, 135(6): 1914-1923.
[15]	Eddi R, Karki A, Shah A, et al. Association of type 2 diabetes and colon adenomas [J]. J Gastrointest Cancer, 2012, 43(1): 87-92.
[16]	Lee JH, Jeon SM, Hong SP, et al. Metformin use is associated with a decreased incidence of colorectal adenomas in diabetic patients with previous colorectal cancer [J]. Dig Liver Dis, 2012, 44(12): 1042-1047.
[17]	Wong P, Weiner MG, Hwang WT, et al. Insulin therapy and colorectal adenomas in patients with diabetes mellitus [J]. Cancer Epidemiol Biomarkers Prev, 2012, 21(10): 1833-1840.
[18]	Cho YH, Ko BM, Kim SH, et al. Does metformin affect the incidence of colonic polyps and adenomas in patients with type 2 diabetes mellitus?[J]. Intest Res, 2014, 12(2): 139-145.
[19]	Kim YH, Noh R, Cho SY, et al. Inhibitory effect of metformin therapy on the incidence of colorectal advanced adenomas in patients with diabetes [J]. Intest Res, 2015, 13(2): 145-152.
[20]	Jain D, Chhoda A, Uribe J. Effect of Insulin and Metformin Combination Treatment on Colon Adenoma and Advanced Adenoma Among DM Ⅱ[J]. J Gastrointest Cancer, 2016, 47(4): 404-408.
[21]	Yang YX. Do diabetes drugs modify the risk of pancreatic cancer?[J]. Gastroenterology, 2009, 137(2): 412-415.
[22]	尚晨，龚凤英，王林. 肥胖相关黑棘皮病的发病机制 [J].国际内分泌代谢杂志, 2016, 36(6): 416-419.
[23]	Pawelczyk L, Spaczynski RZ, Banaszewska B,et al.Metformin therapy increases insulin-like growth factor binding protein-1 in hyperinsulinemic women with polycystic ovary syndrome [J]. Eur J Obstet Gynecol Reprod Biol, 2004, 113(2): 209-213.
[24]	Nair V, Sreevalsan S, Basha R, et al.Mechanism of metformin-dependent inhibition of mammalian target of rapamycin (mTOR) and ras activity in pancreatic cancer [J]. J Biol Chem, 2014, 289(40): 27692-27701.
[25]	Tan BK, Adya R, Chen J, et al. Metformin treatment exerts antiinvasive and antimetastatic effects in human endometrial carcinoma cells [J]. J Clin Endocrinol Metab, 2011, 96(3): 808-816.
[26]	Kwan HT, Chan DW, Cai PC, et al. AMPK activators suppress cervical cancer cell growth through inhibition of DVL3 mediated Wnt/beta-catenin signaling activity [J]. PLoS One, 2013, 8(1): e53597.
[27]	Ben Sahra I, Laurent K, Loubat A, et al.The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level [J]. Oncogene, 2008, 27(25): 3576-3586.
[28]	Tomimoto A, Endo H, Sugiyama M, et al.Metformin suppresses intestinal polyp growth in ApcMin/＋ mice [J]. Cancer Science, 2008, 99(11): 2136-2141.
[29]	Renehan AG, Tyson M, Egger M, et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies [J]. Lancet, 2008, 371(9612): 569-578.
[30]	Grenader T, Goldberg A, Shavit L. Metformin as an addition to conventional chemotherapy in breast cancer [J]. J Clin Oncol, 2009, 27(35): e259.
[31]	Song YK, Park YS, Seon CS, et al. Alcohol drinking increased the risk of advanced colorectal adenomas [J]. Intest Res, 2015, 13(1): 74-79.

[1]	朱连华, 费翔, 韩鹏, 姜波, 李楠, 罗渝昆. 高帧频超声造影在胆囊息肉样病变中的鉴别诊断价值[J]. 中华医学超声杂志（电子版）, 2023, 20(09): 904-910.
[2]	康夏, 田浩, 钱进, 高源, 缪洪明, 齐晓伟. 骨织素抑制破骨细胞分化改善肿瘤骨转移中骨溶解的机制研究[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 329-339.
[3]	张思平, 刘伟, 马鹏程. 全膝关节置换术后下肢轻度内翻对线对疗效的影响[J]. 中华关节外科杂志(电子版), 2023, 17(06): 808-817.
[4]	罗旺林, 杨传军, 许国星, 俞建国, 孙伟东, 颜文娟, 冯志. 开放性楔形胫骨高位截骨术不同植入材料的Meta分析[J]. 中华关节外科杂志(电子版), 2023, 17(06): 818-826.
[5]	代莉, 邓恢伟, 郭华静, 黄芙蓉. 术中持续输注艾司氯胺酮对腹腔镜结直肠癌手术患者术后睡眠质量的影响[J]. 中华普通外科学文献(电子版), 2023, 17(06): 408-412.
[6]	王得晨, 杨康, 杨自杰, 归明彬, 屈莲平, 张小凤, 高峰. 结直肠癌微卫星稳定状态和程序性死亡、吲哚胺2,3-双加氧酶关系的研究进展[J]. 中华普通外科学文献(电子版), 2023, 17(06): 462-465.
[7]	李雄雄, 周灿, 徐婷, 任予, 尚进. 初诊导管原位癌伴微浸润腋窝淋巴结转移率的Meta分析[J]. 中华普通外科学文献(电子版), 2023, 17(06): 466-474.
[8]	唐旭, 韩冰, 刘威, 陈茹星. 结直肠癌根治术后隐匿性肝转移危险因素分析及预测模型构建[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 16-20.
[9]	张生军, 赵阿静, 李守博, 郝祥宏, 刘敏丽. 高糖通过HGF/c-met通路促进结直肠癌侵袭和迁移的实验研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 21-24.
[10]	李婷, 张琳. 血清脂肪酸代谢物及维生素D水平与结直肠癌发生的关系研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 661-665.
[11]	莫闲, 杨闯. 肝硬化患者并发门静脉血栓危险因素的Meta分析[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 678-683.
[12]	刘化胜, 王洪霞, 马正, 王磊. 1例复杂的A3型甲状旁腺腺瘤功能亢进的手术治疗[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 705-706.
[13]	倪文凯, 齐翀, 许小丹, 周燮程, 殷庆章, 蔡元坤. 结直肠癌患者术后发生延迟性肠麻痹的影响因素分析[J]. 中华结直肠疾病电子杂志, 2023, 12(06): 484-489.
[14]	范小彧, 孙司正, 鄂一民, 喻春钊. 梗阻性左半结肠癌不同手术治疗方案的选择应用[J]. 中华结直肠疾病电子杂志, 2023, 12(06): 500-504.
[15]	张政赢, 鞠阳, 刘晓宁. 二甲双胍对2型糖尿病患者大肠腺瘤术后复发的影响[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 485-488.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

Metformin use and the risk of colorectal adenoma: a systematic review and meta-analysis

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

Metformin use and the risk of colorectal adenoma: a systematic review and meta-analysis