CTLA4 tagging polymorphisms and risk of colorectal cancer: a case–control study involving 2,306 subjects
Authors Zou C, Qiu H, Tang W, Wang Y, Lan B, Chen Y
Received 7 May 2018
Accepted for publication 7 June 2018
Published 7 August 2018 Volume 2018:11 Pages 4609—4619
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 3
Editor who approved publication: Dr Sanjeev Srivastava
Chen Zou,1,* Hao Qiu,2,* Weifeng Tang,3 Yafeng Wang,4 Bin Lan,5 Yu Chen6–8
1Department of General Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China; 2Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China; 3Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China; 4Department of Cardiology, The People’s Hospital of Xishuangbanna Dai Autonomous Prefecture Jinghong, Yunnan Province, China; 5Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; 6Cancer Bio-immunotherapy Center, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, Fujian Province, China; 7Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, Fujian Province, China; 8Department of Medical Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, Fujian Province, China
*These authors contributed equally to this work
Background: CTLA4 is a candidate gene which has been implicated in the development of colorectal cancer (CRC).
Patients and Methods: To determine the important role of CTLA-4 polymorphisms on risk of CRC, we genotyped four CTLA-4 tagging polymorphisms and calculated crude/adjusted ORs with their 95% CIs. We recruited 1,003 sporadic CRC cases and 1,303 controls.
Results: The findings suggested that CTLA-4 rs231775 G>A polymorphism increased the risk of CRC (homozygote model: adjusted OR=1.40, 95% CI=1.05–1.87, P=0.022; dominant model: adjusted OR=1.19, 95% CI=1.00–1.41, P=0.047; and recessive model: adjusted OR=1.38, 95% CI=1.05–1.82, P=0.021). In a stratified analysis by site of tumor, this association was also found in colon cancer. We also found that CTLA-4 rs231775 GA/AA genotypes might be associated with an increased risk of CRC in Zhenjiang cohort. In addition, we found the CTLA-4 rs16840252 C>T polymorphism was associated with the risk of colon cancer. Haplotype comparison analysis showed that CTLA-4 Grs3087243Crs16840252Crs733618 Ars231775, Grs3087243Crs16840252Trs733618Ars231775, and other haplotypes increased the risk of CRC (P<0.001, <0.001, and 0.002, respectively).
Conclusion: This study evidences an association of CTLA-4 tagging polymorphisms and haplotypes with CRC risk. Additional well-designed studies with large sample sizes are required to confirm our findings.
Keywords: polymorphism, immune, CTLA-4, tagging, colorectal cancer, susceptibility
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