Oncotarget

Research Papers:

A variant in SIRT2 gene 3′-UTR is associated with susceptibility to colorectal cancer

Yong Yang, Jie Ding, Zhi-Gang Gao and Zhen-Jun Wang _

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Oncotarget. 2017; 8:41021-41025. https://doi.org/10.18632/oncotarget.17460

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Abstract

Yong Yang1, Jie Ding1, Zhi-Gang Gao1 and Zhen-Jun Wang1

1Department of General Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China

Correspondence to:

Zhi-Gang Gao, email: gaozhigangcy@sina.com

Zhen-Jun Wang, email: drzhenjun@163.com

Keywords: SIRT2, polymorphism, colorectal cancer, risk

Received: March 24, 2017     Accepted: April 15, 2017     Published: April 27, 2017

ABSTRACT

SIRT2 is a member of sirtuin family and is associated with cell growth in various cancers. In this study, we searched for variants in functional region of SIRT2 gene and identify rs2015 and rs2241703 in the 3′UTR with minor allele frequency >0.05 in Chinese Han Beijing population from 1000 Genomes Project. We then genotyped these two variants in 842 colorectal cancer (CRC) patients and 1,718 healthy controls using Taqman genotyping assay. Association between variants and risk of CRC is calculated using logistic regression adjusted for sex and age. We found that rs2015C was significantly associated with increased risk of CRC. Compared with CC genotype carriers, CA genotype and AA genotype carriers were associated with CRC susceptibility with OR being 0.79 (95% CI: 0.65–0.96, P = 0.019) and 0.73 (95% CI: 0.58–0.92, P = 0.009), respectively. When stratified by sex and age, significant associations were observed only in males (OR = 0.82, 95% CI: 0.71–0.96, P = 0.010) for rs2015, but not females (OR = 0.90, 95% CI: 0.73–1.10, P = 0.287). It is suggested that the sequence including rs2015C allele lies within a binding site for the full seed region of hsa-miR-376a-5p. Through a systematic interrogate of variants in the functional region of SIRT2 gene, we identified rs2015 was significantly associated with CRC susceptibility, providing new insights into the carcinogenesis of CRC.


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