Association Of EIF3h Expression And Its Gene Polymorphisms With Colorectal Carcinoma

Background:Colorectal cancinoma is a common type of cancer with a considerably poor prognosisand high mortality all over the world. It is difficult to make a diagnosis at earlier stages.Patients with colorectal carcinoma in advanced stages have even poor prognosis, but thedetection of colorectal carcinoma at earlier stages and timely treatment can improve clinicaloutcome. Hence, identification of the factors that influence development of the diseasewould facilitate its prevention or early detection and subsequently result in better prognosis.Eukaryotic translation initiation factor3h (EIF3h) plays a central role in translationinitiation through regulating protein synthesis in maintaining cell growth control. EIF3h hasbeen implicated in a large number of cancerous states. Genome-wide association studiesidentified eIF3h as a causative factor of colorectal carcinoma in European population, andits tag single nucleotide polymorphism (SNP) rs16892766was significantly associated withcolorectal carcinoma. To date there is few EIF3h research on colorectal carcinoma. It is notknown that whether EIF3h is associated with the occurrence of colorectal carcinoma in theHan people of northern China. So it is worth to further elucidate the expression level incolorectal carcinoma and the association of EIF3h polymorphic variants rs16892766withcolorectal cancer susceptibility in the Han people of northern China.Aims:1. To explore the expression of EIF3h in colorectal carcinoma and clinicalpathologicsignificance, and to analyze the relationship between the expression of EIF3h and Ki-67incolorectal carcinoma.2. To investigate the association of EIF3h single-nucleotide polymorphism atrs16892766with colorectal cancer susceptibility in the Han people of northern China．Methods:1. Seventy-six cases of colorectal carcinoma were enrolled in this study, and35case ofcolorectal adenomas and20cases of colorectal mucosal tissues10cm away from carcinoma were used as controls．The expression of EIF3h and Ki-67was detected byimmunohistochemical EnVision method.2. For the genetic polymorphism analysis, the experimental subjects were composed of190patients with colorectal carcinoma and192healthy controls from the306Hospital ofPLA. They were genotyped for rs16892766by polymerase chain reaction and restrictionfragment length polymorphism method (PCR-RFLP)．DNA extracted from blood sampleswas used for genotyping, and the case-control study was used to analyze the association ofgenetic polymorphism with colorectal carcinoma susceptibility．Results:1. The positive rates for EIF3h expression in colorectal carcinomas, adenomas andcolorectal mucosa10cm away from carcinoma were86.84%,31.43%and10%,respectively (P<0.05).2. In colorectal carcinoma, the expression of EIF3h was associated with local invasionand lymph node metastasis (P<0.01), while not associated with sex, age, tumor size andhistological differentiation(P>0.05(.3. There was remarkably positive correlation between the expression of EIF3h andKi-67(r=0.6872, P<0.01).4. Genotype analysis showed that the Han people of northern China did not existrs16892766polymorphism, and this locus was all AA genotype.Conclusions:1. The high expression of EIF3h may play an important role in the pathogenesis andprogression in colorectal carcinoma.2. There is positive association of EIF3h with Ki-67, indicating that EIF3h mightregulate Ki-67．The exact mechanism of regulation remains to be elucidated, but it could behelpful to detect EIF3h expression together with Ki-67for the diagnosis and predictingprognosis of colorectal carcinoma.3. rs16892766A/G genotypes are not associated with colorectal cancer susceptibilityin the Han people of northern China.