Association of <i>UCP2</i> rs659366 polymorphisms with the outcomes of patients after surgery for colorectal cancer

doi:10.3785/j.issn.1008-9292.2018.04.06

J Zhejiang Univ (Med Sci)

2018, Vol. 47

Issue (2): 143-149 DOI: 10.3785/j.issn.1008-9292.2018.04.06

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

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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

Received: 20 January 2018 Published: 24 July 2018

CLC:

R735.3

Corresponding Authors: YANG Yanfang E-mail: fraualice77@sina.com;yang2009@scu.edu.cn

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	JIANG Yanqi
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	LI Yueling
	CHEN Liling
	YAN Jin
	YANG Yanfang

Cite this article:

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.

URL:

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

UCP2 rs659366位点多态性与结直肠癌术后患者生存结局的关系

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

Tab 1 Association of clinical features with the outcomes of patients after surgery for colorectal cancer

Fig 1 Agarose gel electrophoresis of the MluⅠenzyme products of UCP2 rs659366

Tab 2 Association of UCP2 rs659366 polymorphisms with the outcomes of patients after surgery for colorectal cancer


[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.

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