Associations between polymorphisms in the SYK promoter and susceptibility to sporadic colorectal cancer in a Southern Han Chinese population - a short report.
OBJECTIVE
Down-regulated expression of the putative tumor suppressor gene spleen tyrosine kinase (SYK) is strongly associated with the development of various cancers, including colorectal cancer (CRC). SYK gene promoter polymorphisms have been shown to be involved in the pathogenesis of multiple malignant tumors. In this study, we investigated associations of SYK gene promoter polymorphisms with the susceptibility to colorectal cancer development in a Southern Han Chinese population.


METHODS
SNPs in the promoter region of the human SYK gene were identified using in silico analysis tools, linkage disequilibrium analysis, and a search for likely transcription factor binding sites via TFSEARCH in the NCBI SNP database (gene ID: 6850). Based on this information, -803A>T and -534T>C were selected as candidates for further analysis. TaqMan-MGB probe analyses were performed in 567 CRC patients and 569 age- and gender-matched healthy controls for SYK gene promoter genotyping. Associations between CRC risk and SNPs were estimated using an unconditional logistic regression model, and environmental risk factors were included in a multivariate logistic regression model for correction.


RESULTS
The frequencies of the TA and TT genotypes and the T allele of the -803A>T SNP were found to be significantly higher in the CRC patients compared to the healthy individuals of the control group (P=0.020, 0.023, and 0.013, respectively). Synergistic effects between -803A>T genotypes (i.e., TA+TT) and age (≤60 years; P=0.039), male gender (P=0.011), smoking (P=0.005), drinking alcohol (P=0.002), and high BMI (≥24.0 kg/m2; P=0.009) were found to increase the risk to develop CRC by stratified analyses.


CONCLUSIONS
The SYK -803 A>T genotypes TA and TT are independent risk factors for CRC development in Han Chinese in Southern China, and an association with TA+TT genotypes appears predominant among younger patients, male patients, patients with a high BMI, and patients who smoke or drink alcohol.
Guangdong Institute of Gastroenterology and the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Hui
H
Peng
Jun
J
Huang
Ying
Y
Hu
Yisheng
Y
Wei
Huanliang
H
Liu
Meijin
M
Huang
Lei
L
Wang
Jianping
J
Wang
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D000072377:Syk Kinase
D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase