Association of ITGA3 gene polymorphisms with susceptibility and clinicopathological characteristics of osteosarcoma
MEDICAL ONCOLOGY
Authors: Yang, Wu; He, Maolin; Zhao, Jinmin; Wang, Zhe
Abstract
Integrin controls cell adhesion to extracellular matrix and plays an important role in regulating the proliferation and apoptosis of cells. In order to explore the role of ITGA3 gene polymorphisms in the pathogenesis and clinicopathological characteristics of osteosarcoma, we embarked on a study including a group of 118 patients and a group of 126 healthy controls. TaqMan PCR genotyping technology was used to detect the genotypes of ITGA3 gene SNPs (rs2230392, rs2285524 and rs16948627) in the peripheral blood. Then, associations of the SNP (rs2230392, rs2285524 and rs16948627) genotypes with the incidence risk and tumor characteristics of osteosarcoma were evaluated. A significant difference (P = 0.02) in the genotype frequency distribution of rs2230392 was observed between case and control groups. The analysis showed that patients carrying AA genotype had a higher risk of osteosarcoma (OR 2.34, 95 % CI 1.18-4.64) than those with GG genotype. Regarding rs2230392, men carrying AA genotype had a higher risk of osteosarcoma (OR 3.37, 95 % CI 1.25-9.11). Compared with those with GG genotype, patients carrying AA genotype had a twofold increased risk of osteosarcoma metastasis (OR 2.46, 95 % CI 1.09-5.57). Survival analysis showed that for rs2230392, survival time of osteosarcoma patients with three different genotypes was significantly different. Polymorphisms of ITGA3 gene rs2230392 may affect the incidence, metastasis and survival of osteosarcoma, which may clinically become a new target for predicting the risk of osteosarcoma, and have prognostic value.
Polymorphisms in predicted microRNA-binding sites in integrin genes and breast cancer: ITGB4 as prognostic marker
CARCINOGENESIS
Authors: Brendle, Annika; Lei, Haixin; Brandt, Andreas; Johansson, Robert; Enquist, Kerstin; Henriksson, Roger; Hemminki, Kari; Lenner, Per; Foersti, Asta
Abstract
Integrins control the cell attachment to the extracellular matrix and play an important role in mediating cell proliferation, migration and survival. A number of important cancer-associated integrin genes can be regulated by microRNAs (miRNAs) that bind to their target sites in the 3' untranslated regions. We examined the effect of single-nucleotide polymorphisms (SNPs) in predicted miRNA target sites of six integrin genes (ITGA3, ITGA6, ITGAv, ITGB3, ITGB4 and ITGB5) on breast cancer (BC) risk and clinical outcome. Six SNPs were genotyped in 749 Swedish incident BC cases with detailed clinical data and up to 15 years of follow-up together with 1493 matched controls. We evaluated associations between genotypes and BC risk and clinical tumour characteristics. Survival probabilities were compared between different subgroups. As a novel finding, several SNPs seemed to associate with the hormone receptor status. The strongest association was observed between the A allele of the SNP rs743554 in the ITGB4 gene and oestrogen receptor-negative tumours [odds ratio 2.09, 95% confidence intervals (CIs) 1.19-3.67]. The same SNP was associated with survival. The A allele carriers had a worse survival compared with the wild-type genotype carriers (hazard ratio 2.11, 95% CIs 1.21-3.68). The poor survival was significantly associated with the aggressive tumour characteristics: high grade, lymph node metastasis and high stage. None of the SNPs was significantly associated with BC risk. As the ITGB4 SNP seems to influence tumour aggressiveness and survival, it may have prognostic value in the clinic.