Please wait a minute...
浙江大学学报(医学版)  2018, Vol. 47 Issue (2): 143-149    DOI: 10.3785/j.issn.1008-9292.2018.04.06
原著     
UCP2 rs659366位点多态性与结直肠癌术后患者生存结局的关系
蒋滟蕲1(),杨雅兰1,杨婷1,李玥伶2,陈莉玲3,燕锦4,杨艳芳1,*()
1. 四川大学华西公共卫生学院流行病与卫生统计学系, 四川 成都 610041
2. 成都市疾病预防控制中心传染病防治科, 四川 成都 610041
3. 重庆市疾病预防控制中心慢性非传染性疾病预防控制所, 重庆 400042
4. 四川省肿瘤医院肠道外科, 四川 成都 610041
Association of UCP2 rs659366 polymorphisms with the outcomes of patients after surgery for colorectal cancer
JIANG Yanqi1(),YANG Yalan1,YANG Ting1,LI Yueling2,CHEN Liling3,YAN Jin4,YANG Yanfang1,*()
1. Department of Epidemiology and Biostatistics, West China School of Public Health, Sichuan University, Chengdu 610041, China
2. Department of Infectious Disease Control and Prevention, Chengdu Center for Disease Control and Prevention, Chengdu 610041, China
3. Institute for Chronic Non-communicable Disease Control and Prevention, Chongqing Center for Disease Control and Prevention, Chongqing 400042, China
4. Department of Intestinal Surgery, Sichuan Cancer Hospital, Chengdu 610041, China
 全文: PDF(1003 KB)   HTML( 9 )
摘要:

目的: 探讨UCP2 rs659366位点多态性与结直肠癌术后患者生存结局的关系。方法: 选择2010年3月至2013年7月于四川省肿瘤医院肠道外科行手术治疗且资料完整的原发性结直肠癌患者501例,随访术后生存结局。采用限制性片断长度多态性PCR检测UCP2 rs659366位点的基因多态性。采用log-rank检验分析患者主要临床特征对生存结局的影响;采用Cox比例风险回归模型分析UCP2 rs659366位点基因多态性与患者生存结局之间的相关性。结果: 本研究中位随访时间为44.23(0.13~78.53)个月,501例结直肠癌患者中101例失访,失访率为20.2%。log-rank检验结果显示,肿瘤部位、TNM分期、脉管侵犯、神经侵犯、术前癌胚抗原水平与结直肠癌患者的生存结局相关(P < 0.05或P < 0.01)。UCP2 rs659366位点AA、GA和GG基因型结直肠癌患者的存活率分别为62.7%、69.9%和75.5%。多因素Cox比例风险回归模型分析结果显示:共显性遗传模型中UCP2 rs659366位点AA基因型是结直肠癌患者生存结局的危险基因型,其不良生存结局的风险是GG基因型的1.823倍;显性遗传模型中UCP2 rs659366位点GG+GA基因型与结直肠癌患者生存结局有关,其不良生存结局的风险是GG基因型的1.498倍;在加性遗传模型中,UCP2 rs659366位点GA基因型患者不良生存结局的风险是GG基因型患者的1.787倍,而AA基因型患者不良生存结局的风险是GA基因型患者的1.787倍。结论: UCP2 rs659366位点基因多态性可能是影响结直肠癌术后患者生存结局的因素。

关键词: 结直肠肿瘤/外科学手术后期间线粒体膜转运蛋白质类多态性, 单核苷酸基因型预后    
Abstract:

Objective: To explore the association between UCP2 rs659366 polymorphisms and the outcomes of patients after surgery for colorectal cancer. Methods: The study was conducted among a cohort of 501 patients with primary colorectal cancer who had surgery in Sichuan Cancer Hospital during March 2010 and July 2013. The outcomes of the patients were followed up. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect UPC2 rs659366 genotypes. The log-rank test was performed to analyze the effects of clinical features on patients' outcomes. The correlation between UCP2 rs659366 polymorphisms and the outcomes of patients was analyzed using the Cox proportional hazard model. Results: In this study, the median of follow-up time was 44.23(0.13-78.53)months, and 101 out of 501 (20.2%) patients failed to follow-up. The log-rank test showed the tumor site, TNM stage, vascular invasion, perineural invasion and the preoperative carcino-embryonic antigen(CEA) level were significantly associated with the outcome of colorectal cancer (P < 0.05 or P < 0.01). The overall survival rate of patients with AA, GA and GG genotypes were 62.7%, 69.9% and 75.5%, respectively. Multivariate analysis according to Cox proportional hazard model taking the GG genotype as the reference indicated that the AA genotype increased risks for survival of patients (HR=1.823); under the dominant genetic model taking GG genotype as reference, GA+AA genotypes increased risks for the poorer outcomes of patients (HR=1.498); the addictive genetic model showed that allele A increased the hazard for the poorer outcomes (HR=1.787). Conclusion: The UCP2 rs659366 polymorphisms are significantly associated with the outcome of patients with colorectal cancer.

Key words: Colorectal neoplasms/surgery    Postoperative period    Mitochondrial membrane transport proteins    Polymorphism, single nucleotide    Genotype    Prognosis
收稿日期: 2018-01-20 出版日期: 2018-07-24
:  R735.3  
基金资助: 国家自然科学基金(81102196);教育部博士点专项科研基金(20090181120019)
通讯作者: 杨艳芳     E-mail: fraualice77@sina.com;yang2009@scu.edu.cn
作者简介: 蒋滟蕲(1993-), 女, 硕士研究生, 主要从事肿瘤分子流行病学研究; E-mail: fraualice77@sina.com; https://orcid.org/0000-0002-8679-4336
服务  
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章  
蒋滟蕲
杨雅兰
杨婷
李玥伶
陈莉玲
燕锦
杨艳芳

引用本文:

蒋滟蕲,杨雅兰,杨婷,李玥伶,陈莉玲,燕锦,杨艳芳. UCP2 rs659366位点多态性与结直肠癌术后患者生存结局的关系[J]. 浙江大学学报(医学版), 2018, 47(2): 143-149.

JIANG Yanqi,YANG Yalan,YANG Ting,LI Yueling,CHEN Liling,YAN Jin,YANG Yanfang. Association of UCP2 rs659366 polymorphisms with the outcomes of patients after surgery for colorectal cancer. J Zhejiang Univ (Med Sci), 2018, 47(2): 143-149.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2018.04.06        http://www.zjujournals.com/med/CN/Y2018/V47/I2/143

[n(%)]
临床特征 n 存活
log-rank检验,*P<0.05,**P<0.01.
性别 225 159(70.7)
175 123(70.3)
年龄段(岁) <40 30 19(63.3)
40~<60 187 131(70.1)
≥60 183 132(72.1)
肿瘤部位* 结肠 147 95(64.6)
直肠 253 187(73.9)
细胞分级 低级别 324 234(72.2)
高级别 76 48(63.2)
TNM分期** 63 53(84.1)
124 109(87.9)
153 110(71.9)
60 10(16.7)
脉管侵犯** 52 29(55.8)
348 253(72.7)
神经侵犯** 43 22(51.2)
357 260(72.8)
术前癌胚抗原水平 ≤5 260 201(77.3)
(ng/mL)** >5 140 81(57.9)
术后辅助治疗 333 237(71.2)
67 45(67.2)
手术类型 开腹手术 376 261(69.4)
腹腔镜 24 21(87.5)
表 1  400例结直肠癌患者临床特征与生存结局的关系
图 1  典型病例UCP2 rs659366位点MluⅠ酶切产物琼脂凝胶电泳图
遗传模型 基因型 单因素Cox比例风险回归模型 多因素Cox比例风险回归模型*
HR(95%CI) P HR(95%CI) P
“—”无相关数据;*调整因素为性别、年龄、肿瘤部位、细胞分级、TNM分期、脉管侵犯、神经侵犯、术前癌胚抗原水平、术后是否辅助治疗和手术类型.
共显性 GG 1.000 1.000
GA 1.293(0.844~1.980) >0.05 1.382(0.900~2.122) >0.05
AA 1.683(1.020~2.776) <0.05 1.823(1.094~3.037) <0.05
显性 GG 1.000 1.000
GA+AA 1.401(0.941~2.087) >0.05 1.498(1.002~2.240) <0.05
隐性 GG+GA 1.000 1.000
AA 1.445(0.946~2.210) >0.05 1.503(0.976~2.314) >0.05
超显性 GG+AA 1.000 1.000
GA 1.056(0.736~1.516) >0.05 1.099(0.765~1.580) >0.05
加性 1.686(1.022~2.781) <0.05 1.787(1.065~2.998) <0.05
表 2  不同遗传模型下UCP2 rs659366位点基因多态性与结直肠癌术后患者生存结局的关系
1 FERLAY J , SOERJOMATARAM I , DIKSHIT R et al. Cancer incidence and mortality worldwide:sources, methods and major patterns in GLOBOCAN 2012[J]. Int J Cancer, 2015, 136 (5): E359- E386
doi: 10.1002/ijc.29210
2 CHEN W , ZHENG R , BAADE P D et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66 (2): 115- 132
doi: 10.3322/caac.21338
3 BOSETTI C , LEVI F , ROSATO V et al. Recent trends in colorectal cancer mortality in Europe[J]. Int J Cancer, 2011, 129 (1): 180- 191
doi: 10.1002/ijc.v129.1
4 GUO P , HUANG Z L , YU P et al. Trends in cancer mortality in China:an update[J]. Ann Oncol, 2012, 23 (10): 2755- 2762
doi: 10.1093/annonc/mds069
5 CUEZVA J M , KRAJEWSKA M , DE HEREDIA M L et al. The bioenergetic signature of cancer:a marker of tumor progression[J]. Cancer Res, 2002, 62 (22): 6674- 6681
6 DERDAK Z , MARK N M , BELDI G et al. The mitochondrial uncoupling protein-2 promotes chemo-resistance in cancer cells[J]. Cancer Res, 2008, 68 (8): 2813- 2819
doi: 10.1158/0008-5472.CAN-08-0053
7 HEIDARI J , AKRAMI S M , HESHMAT R et al. Association study of the -866G/A UCP2 gene promoter polymorphism with type 2 diabetes and obesity in a Tehran population:a case control study[J]. Arch Iran Med, 2010, 13 (5): 384- 390
8 YAHAGI M , OKABAYASHI K , HASEGAWA H et al. The worse prognosis of right-sided compared with left-sided colon cancers:a systematic review and meta-analysis[J]. J Gastrointest Surg, 2016, 20 (3): 648- 655
doi: 10.1007/s11605-015-3026-6
9 JESS T , RUNGOE C , PEYRIN-BIROULET L . Risk of colorectal cancer in patients with ulcerative colitis:a meta-analysis of population-based cohort studies[J]. Clin Gastroenterol Hepatol, 2012, 10 (6): 639- 645
doi: 10.1016/j.cgh.2012.01.010
10 TSAI P L , SU W J , LEUNG W H et al. Neutrophil-lymphocyte ratio and CEA level as prognostic and predictive factors in colorectal cancer:a systematic review and meta-analysis[J]. J Cancer Res Ther, 2016, 12 (2): 582- 589
doi: 10.4103/0973-1482.144356
11 ATSUSHI I , MITSUYOSHI O , KAZUYA Y et al. Long-term outcomes and prognostic factors of patients with obstructive colorectal cancer:a multicenter retrospective cohort study[J]. World J Gastroenterol, 2016, 22 (22): 5237- 5245
doi: 10.3748/wjg.v22.i22.5237
12 SASAKI T , ITO Y , OHUE M et al. Postoperative chemoradiotherapy after local resection for high-risk T1 to T2 low rectal cancer:results of a single-arm, multi-institutional, phase Ⅱ clinical trial[J]. Dis Colon Rectum, 2017, 60 (9): 914- 921
doi: 10.1097/DCR.0000000000000870
13 WU Q , WEI M , YE Z et al. Laparoscopic colectomy versus open colectomy for treatment of transverse colon cancer:a systematic review and meta-analysis[J]. J Laparoendosc Adv Surg Tech A, 2017, 27 (10): 1038- 1050
doi: 10.1089/lap.2017.0031
14 KREMPLER F , ESTERBAUER H , WEITGASSER R et al. A functional polymorphism in the promoter of UCP2 enhances obesity risk but reduces type 2 diabetes risk in obese middle-aged humans[J]. Diabetes, 2002, 51 (11): 3331- 3335
doi: 10.2337/diabetes.51.11.3331
15 SESTI G , CARDELLINI M , MARINIM A et al. A common polymorphism in the promoter of UCP2 contributes to the variation in insulin secretion in glucose-tolerant subjects[J]. Diabetes, 2003, 52 (5): 1280- 1283
doi: 10.2337/diabetes.52.5.1280
16 WANG H , CHU W S , LU T et al. Uncoupling protein-2 polymorphisms in type 2 diabetes, obesity, and insulin secretion[J]. Am J Physiol Endocrinol Metab, 2004, 286 (1): E1- E7
doi: 10.1152/ajpendo.00231.2003
17 HORIMOTO M , RESNICK M B , KONKIN T A et al. Expression of uncoupling protein-2 in human colon cancer[J]. Clin Cancer Res, 2004, 10 (18 Pt 1): 6203- 6207
18 HU X, YUAN P, YAN J, et al. Gene polymorphisms of ADIPOQ +45T>G, UCP2-866G>A, and FABP2 Ala54Thr on the risk of colorectal cancer: a matched case-control study[J/OL]. PLoS One, 2013, 8(6): e67275.
[1] 米爽,吴燕君,洪正华,王章富,冯兴兵,郑光彬. TLR4/MyD88/NF-κB通路基因及相关炎症因子在继发性脊髓损伤患者中的表达[J]. 浙江大学学报(医学版), 2019, 48(6): 609-616.
[2] 王雅芸,陈原,杨蒙蒙,习芳芳,占琪涛,蒋颖,赵柏惠,罗琼. 淋巴水囊瘤或颈部组织增厚胎儿预后分析[J]. 浙江大学学报(医学版), 2019, 48(4): 434-438.
[3] 童凡,杨茹莱,刘畅,吴鼎文,张婷,黄新文,洪芳,钱古柃,黄晓磊,周雪莲,舒强,赵正言. 新生儿酪氨酸血症筛查及基因谱分析[J]. 浙江大学学报(医学版), 2019, 48(4): 459-464.
[4] 钟晚思, 陈智才, 陈红芳, 徐冬娟, 王志敏, 胡海芳, 吴承龙, 张晓玲, 马小董, 王亚仙, 胡海涛, 楼敏, 浙江省缺血性脑卒中静脉溶栓的临床行为干预研究协作组 . 院前急救医疗服务对缺血性脑卒中患者静脉溶栓预后的影响[J]. 浙江大学学报(医学版), 2019, 48(3): 241-246.
[5] 张聪聪, 楼敏, 陈智才, 陈红芳, 徐冬娟, 王志敏, 胡海芳, 吴承龙, 张晓玲, 马小董, 王亚仙, 胡海涛, 浙江省缺血性脑卒中静脉溶栓的临床行为干预研究协作组 . 医院内缺血性脑卒中患者静脉溶栓时间及预后分析[J]. 浙江大学学报(医学版), 2019, 48(3): 260-266.
[6] 陈红芳, 龚筱弦, 徐冬娟, 王志敏, 胡海芳, 吴承龙, 张晓玲, 马小董, 王亚仙, 胡海涛, 楼敏, 陈智才, 浙江省缺血性脑卒中静脉溶栓的临床行为干预研究协作组 . 治疗时间提前可改善缺血性脑卒中患者再灌注治疗的预后[J]. 浙江大学学报(医学版), 2019, 48(3): 247-253.
[7] 泮飞虎, 楼敏, 陈智才, 陈红芳, 徐冬娟, 王志敏, 胡海芳, 吴承龙, 张晓玲, 马小董, 王亚仙, 胡海涛, 浙江省缺血性脑卒中静脉溶栓的临床行为干预研究协作组 . 不同工作时间段就诊对缺血性脑卒中患者静脉溶栓预后的影响[J]. 浙江大学学报(医学版), 2019, 48(3): 267-274.
[8] 杜东芬,朱丽霞,王云贵,叶琇锦. 肾母细胞瘤1基因表达及其对急性髓系白血病患者预后的预测价值[J]. 浙江大学学报(医学版), 2019, 48(1): 50-57.
[9] 王安奇,刘欣跃. CXCL12及CXCR4基因多态性与冠心病发病风险和冠状动脉狭窄程度的相关性[J]. 浙江大学学报(医学版), 2018, 47(5): 514-519.
[10] 楼叶琳,周一敏,鲁红,吕卫国. 宫颈锥切术后孕妇早产预测模型的建立[J]. 浙江大学学报(医学版), 2018, 47(4): 351-356.
[11] 陈倩,刘露,张静静,韩赛,崔保霞,张友忠,孔北华. 237例宫颈腺癌及腺鳞癌患者临床特征及预后分析[J]. 浙江大学学报(医学版), 2018, 47(4): 357-361.
[12] 陈挺,赵正言,蒋萍萍,舒强. 高苯丙氨酸血症表型与基因型研究进展[J]. 浙江大学学报(医学版), 2018, 47(3): 219-226.
[13] 王佳静,谷海瀛. 幽门螺杆菌的基因分型技术及其应用[J]. 浙江大学学报(医学版), 2018, 47(1): 97-103.
[14] 丁元,孙忠权,章文燕,章向英,姜源聪,严盛,王伟林. 腹腔镜胰体尾切除术患者围手术期加速康复管理及效果评估[J]. 浙江大学学报(医学版), 2017, 46(6): 625-629.
[15] 潘静颖 等. PET-CT与乳腺癌分子病理分型、治疗反应及预后的相关性研究进展[J]. 浙江大学学报(医学版), 2017, 46(5): 473-480.