Two variants on T2DM susceptible gene HHEX are associated with CRC risk in a Chinese population.
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.
Department of Oncology, PuAi Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Rui
R
Sun
Department of Oncology, PuAi Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Jian-Ping
JP
Liu
Department of Oncology, PuAi Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Chang
C
Gao
Department of Clinical Laboratory, PuAi Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ying-Ying
YY
Xiong
Department of Oncology, PuAi Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Min
M
Li
Department of Oncology, PuAi Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ya-Ping
YP
Wang
Department of Oncology, PuAi Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yan-Wei
YW
Su
Department of Endocrinology, Wuhan PuAi Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Mei
M
Lin
Department of Oncology, PuAi Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
An-Li
AL
Jiang
Department of Oncology, PuAi Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ling-Fan
LF
Xiong
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Yan
Y
Xie
Department of Oncology, PuAi Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Jue-Ping
JP
Feng
D044466:Asian People / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*
C078492:HHEX protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors
HHEX; colorectal cancer; genetic variants; type 2 diabetes mellitus