Associations of polymorphisms in NAT2 gene with risk and metastasis of osteosarcoma in young Chinese population

OncoTargets and Therapy Dovepress open access to scientific and medical research Original Research OncoTargets and Therapy downloaded from https://www.dovepress.com/ by 213.32.59.121 on 12-Jul-2018 For personal use only. Open Access Full Text Article Associations of polymorphisms in NAT2 gene with risk and metastasis of osteosarcoma in young Chinese population This article was published in the following Dove Press journal: OncoTargets and Therapy 22 September 2015 Number of times this article has been viewed Zhengxiang Huang 1 Li Yuan 2 Zhenghui Jiang 3,4 Dongliang Wang 1 Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 2Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 3 Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 4Department of Orthopedics, The First People’s Hospital of Wenling, Wenling, People’s Republic of China 1 Introduction Correspondence: Dongliang Wang Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, People’s Republic of China Tel +86 21 2507 8899 Email Osteosarcoma is the most common malignant tumor of bone in childhood and adolescence and is associated with early metastatic potential and a poor prognosis.1 Albeit the fact that quite a few studies on osteosarcoma are emerging these days, its tumorigenesis and roles that predict outcomes or malignancy risk are still poorly revealed. Genetic factors, such as single-nucleotide polymorphisms (SNPs), may play a role in the tumorigenesis and progression of osteosarcoma. Better understanding on genes factors is needed to identify the prognostic markers and therapeutic targets. NAT2 gene encodes a Phase II xenobiotic-metabolizing enzyme.2 As a Phase II metabolizing enzyme, NAT2 catalyzes the metabolic activation of aromatic and heterocyclic amine carcinogens via O-acetylation and N-acetylation. Given that a single-nucleotide alteration causing substitution of amino acid residues may play a role in affecting the biological activity of the gene product,3 polymorphism in NAT2 gene may be correlated with cancer risk and outcome. A substantial number of researches on different ethnic populations have revealed that NAT2 alleles have an impact on the risk to a variety of malignancies, including acute lymphoblastic leukemia,4 lung squamous carcinoma,5 urinary bladder cancer,6 gastric cancer,7 and so on. However, to the best of our knowledge, there is still no study on the correlation between NAT2 polymorphisms and osteosarcoma incidence. Assuming that osteosarcoma risk can be linked to ionizing radiation exposure, it is plausible that genetic alterations in NAT2 gene may modulate osteosarcoma incidence. 2675 submit your manuscript | www.dovepress.com OncoTargets and Therapy 2015:8 2675–2680 Dovepress © 2015 Huang et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php http://dx.doi.org/10.2147/OTT.S92275 Powered by TCPDF (www.tcpdf.org) Abstract: Osteosarcoma is the most common primary malignancy of bone in young individuals. Genetic factors may play an important role in the tumorigenesis of osteosarcoma. Here we carried out a case-control study to investigate seven NAT2 single-nucleotide polymorphisms (rs1799929, rs120, rs1041983, rs1801280, rs1799930, rs1799931, and rs1801279) on the risk and prognosis of osteosarcoma. This study included 260 young osteosarcoma cases and 286 controls. The TaqMan method was used to determine genotypes. We found that rs1799931 G.A polymorphisms were associated with a decreased risk of osteosarcoma in young Chinese population, and rs1041983 CT genotype seemed to play a protective role in the risk of osteosarcoma. However, further analysis showed that rs1041983 polymorphisms were associated with an elevated risk of tumor metastasis, predicting poor prognosis. This study provided the first evidence for the associations between NAT2 polymorphisms and osteosarcoma risk and metastasis in Chinese population. Keywords: osteosarcoma, NAT2, SNP, metastasis, susceptibility Dovepress OncoTargets and Therapy downloaded from https://www.dovepress.com/ by 213.32.59.121 on 12-Jul-2018 For personal use only. Huang et al Hence, we launched a project on NAT2 polymorphisms in children and teenaged osteosarcoma patients in four institutions in 2007, in order to unveil the puzzle that whether NAT2 polymorphisms were associated with osteosarcoma incidence and risk of tumor metastasis in young-aged individuals. In this case-control study, we performed genotyping analyses of seven NAT2 tagging SNPs in 260 osteosarcoma patients and 286 controls in East China population, who share similar diet customs and living environment. Materials and methods Ethics approval This case-control study was approved by the Ethics Committees of four institutions (Xinhua Hospital, The Second Affiliated Hospital of Zhejiang University School of Medicine, The First People’s Hospital of Wenling, and Fudan University) and was performed according to the Declaration of Helsinki. Informed consents were obtained from all participants or their guardians involved in the study. Study subject This study included 260 newly diagnosed osteosarcoma cases under the age of 20 years and 280 cancer-free controls, in the period between February 2007 and March 2012. All individuals involved in this study were specified as Chinese Han people. Diagnosis was confirmed by histopathological examination before radiotherapy and chemotherapy. All the included osteosarcoma cases underwent proper surgical operations by experienced surgeons, as well as nonsurgical therapeutic regimens according to the protocol. Detailed information such as tumor location and stage of osteosarcoma was obtained from medical records. All included patients were followed up regularly from the time of diagnosis for at least 36 months. The cancer-free controls were all recruited from trauma-induced fracture cases and were matched to osteosarcoma subjects by age and sex. Samples of 10 mL venous blood were obtained from each individual, and tumor tissues were conserved in liquid nitrogen. DNA isolation DNA was isolated from blood samples, which were collected into EDTA tubes, by using standard phenol–chloroform extraction and ethanol precipitation. DNA Blood Mini Kit (Qiagen, Berlin, Germany) was also used to isolate genomic (...truncated)