Two variants on T2DM susceptible gene HHEX are associated with CRC risk in a Chinese population
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Rui Sun1,*, Jian-Ping Liu1,*, Chang Gao1, Ying-Ying Xiong2, Min Li1, Ya-Ping Wang1, Yan-Wei Su1, Mei Lin3, An-Li Jiang1, Ling-Fan Xiong1, Yan Xie4, Jue-Ping Feng1
1Department of Oncology, PuAi Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2Department of Clinical Laboratory, PuAi Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3Department of Endocrinology, Wuhan PuAi Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
4Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
*These authors have contributed equally to this work
Jue-Ping Feng, email: [email protected]
Keywords: type 2 diabetes mellitus, HHEX, colorectal cancer, genetic variants
Received: November 07, 2015 Accepted: March 28, 2016 Published: April 20, 2016
Increasing amounts of evidence has demonstrated that T2DM (Type 2 Diabetes Mellitus) patients have increased susceptibility to CRC (colorectal cancer). As HHEX is a recognized susceptibility gene in T2DM, this work was focused on two SNPs in HHEX, rs1111875 and rs7923837, to study their association with CRC. T2DM patients without CRC (T2DM-only, n=300), T2DM with CRC (T2DM/CRC, n=135), cancer-free controls (Control, n=570), and CRC without T2DM (CRC-only, n=642) cases were enrolled. DNA samples were extracted from the peripheral blood leukocytes of the patients and sequenced by direct sequencing. The χ2 test was used to compare categorical data. We found that in T2DM patients, rs1111875 but not the rs7923837 in HHEX gene was associated with the occurrence of CRC (p= 0.006). for rs1111875, TC/CC patients had an increased risk of CRC (p=0.019, OR=1.592, 95%CI=1.046-2.423). Moreover, our results also indicated that the two variants of HEEX gene could be risk factors for CRC in general population, independent on T2DM (p< 0.001 for rs1111875, p=0.001 for rs7923837). For rs1111875, increased risk of CRC was observed in TC or TC/CC than CC individuals (p<0.001, OR= 1.780, 95%CI= 1.385-2.287; p<0.001, OR= 1.695, 95%CI= 1.335-2.152). For rs7923837, increased CRC risk was observed in AG, GG, and AG/GG than AA individuals (p< 0.001, OR= 1.520, 95%CI= 1.200-1.924; p=0.036, OR= 1.739, 95%CI= 0.989-3.058; p< 0.001, OR= 1.540, 95%CI= 1.225-1.936). This finding highlights the potentially functional alteration with HHEX rs1111875 and rs7923837 polymorphisms may increase CRC susceptibility. Risk effects and the functional impact of these polymorphisms need further validation.
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