A genetic variant in miR-146a modifies colorectal cancer susceptibility in a Chinese population
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TOXICOGENOMICS
A genetic variant in miR-146a modifies colorectal cancer susceptibility in a Chinese population Lan Ma • Lingjun Zhu • Dongying Gu Haiyan Chu • Na Tong • Jinfei Chen • Zhengdong Zhang • Meilin Wang
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Received: 26 September 2012 / Accepted: 18 December 2012 / Published online: 10 January 2013 Ó Springer-Verlag Berlin Heidelberg 2013
Abstract MicroRNAs (miRNAs) are a family of endogenous, small, noncoding RNA molecules that involved in a wide range of biological processes including differentiation, proliferation, and apoptosis. A polymorphism G[C (rs2910164) is located in the stem region opposite to the mature miR-146a sequence. In our study, we investigated whether rs2910164 is associated with the risk of colorectal cancer (CRC) in a Chinese population. We genotyped the rs2910164 polymorphism using TaqMan method and evaluated the association with CRC risk in a case–control study, including 1,147 CRC patients and 1,203 cancer-free controls. Logistic regression models were used to assess the genetic effects on the development of CRC. Overall, we found that rs2910164 was significantly associated with
Lan Ma, Lingjun Zhu, and Dongying Gu are contributed equally to this work. L. Ma M. Wang (&) Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China e-mail: [email protected] L. Ma H. Chu N. Tong Z. Zhang (&) M. Wang Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, 818 East Tianyuan Road, Nanjing 211166, China e-mail: [email protected] L. Zhu Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China D. Gu J. Chen Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
the reduced CRC risk [GC/CC versus GG: adjusted odds ratio (OR) = 0.78, 95 % confidence intervals (CIs) = 0.66–0.93]. In the stratification analysis, this decreased risk was also pronounced among non-smokers (0.75, 0.61–0.93), non-drinkers (0.77, 0.63–0.94), and no family history of cancer (0.79, 0.65–0.95). Furthermore, GC/CC genotypes were associated with reduced CRC susceptibility in intermediate differentiated CRC (0.75, 0.62– 0.90), and similar effect was observed in patients with the advanced stage tumor (Dukes C and D) (0.76, 0.61–0.93). In conclusion, our results suggest that miR-146a rs2910164 may contribute to the susceptibility to CRC in a Chinese population. Further larger populationbased prospective and functional studies are needed to validate our findings. Keywords miR-146a Polymorphism Colorectal cancer Genetic susceptibility
Introduction Colorectal cancer (CRC), the second most common cancer in women and the third in men, is an important health problem worldwide (Jemal et al. 2011). The incidence of CRC is generally high in Australia/New Zealand and North America and low in Africa and South-C
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