PIK3CA and AKT Gene Polymorphisms in Susceptibility to Osteosarcoma in a Chinese Population

Mao-Lin He,Yang Wu,Ying-Bin Chen,Jin-Min Zhao,Zhe Wang

doi:10.7314/apjcp.2013.14.9.5117

Abstract

To explore the association between PIK3CA and AKT single nucleotide polymorphisms(SNP) and osteosarcoma susceptibility. TaqMan polymerase chain reaction(PCR) was used to detect the genotypes of SNPs (rs7646409, rs6973569 and rs9866361) in peripheral blood samples from 59 patients with osteosarcoma and from 63 healthy controls. Unconditional logistic regression was used to analyze the correlation between SNPs and osteosarcoma risk. No statistically significant difference was found between osteosarcoma patients and healthy controls in the genotype of AKT rs6973569 (P = 0.7). However, after stratified analysis, the genotype AA of AKT rs6973569 carried a higher risk of osteosarcoma metastasis (OR:2.94, 95%CL:1.00-8.59); the difference of rs7646409 genotype distributions between the case and control groups was statistically significant (P = 0.032). Taking genotype TT as a reference, the risk of osteosarcoma increased three fold in patients with genotype CC (OR:3.47, 95%CL:1.26-9.56). A statistically significant difference was found between the alleles C and T (P=0.005). Further analysis showed that the risk factor was more pronounced in male patients with Enneking's stage IIB and osteoblastic osteosarcoma. PIK3CA rs9866361 did not fit Hardy-Weinberg equilibrium (P < 0.05). Genotype CC in locus PIK3CA rs7646409 may increase the risk of osteosarcoma in the Chinese population.

Highlights

Osteosarcoma is the most common primary malignant bone tumors (Hameed et al, 2011), the incidence is about 4.7 persons per million population per year, of which in men is slightly higher than in women (Linabery et al, 2008)
The genotypes of SNPs detected by TaqMan PCR were shown in Figure 1.Genotype frequencies of PIK3CA rs7646409 and AKT rs6973569 in the control group were in accordance with HardyWeinberg equilibrium (HWE) (P >0.25, P >0.05), but PIK3CA rs9866361 did not fit HWE (P < 0.05)
More and more evidence confirms that polymorphisms in PI3K/Akt signaling pathway play an important role in proliferation, apoptosis and metastasis (Liu et al, 2009; Courtney et al, 2010; Wang et al, 2012)

Summary

Introduction

Osteosarcoma is the most common primary malignant bone tumors (Hameed et al, 2011), the incidence is about 4.7 persons per million population per year, of which in men is slightly higher than in women (Linabery et al, 2008). Results: No statistically significant difference was found between osteosarcoma patients and healthy controls in the genotype of AKT rs6973569 (P = 0.7).

Results

Conclusion