Interactions of miR - 34b / c and TP - 53 polymorphisms on the risk of nasopharyngeal carcinoma

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RESEARCH ARTICLE

Interactions of miR-34b/c and TP-53 polymorphisms on the risk of nasopharyngeal carcinoma Lijuan Li & Jian Wu & Xiutian Sima & Peng Bai & Wei Deng & Xueke Deng & Lin Zhang & Linbo Gao

Received: 10 December 2012 / Accepted: 4 March 2013 / Published online: 17 March 2013 # International Society of Oncology and BioMarkers (ISOBM) 2013

Abstract Growing evidence indicates that tumor suppressor gene TP-53 and non-coding RNA miR-34b/c independently and/or jointly play crucial roles in carcinogenesis. We hypothesized that the polymorphisms of rs4938723 in the promoter region of pri-miR-34b/c and TP-53 Arg72-Pro may be related to the risk of nasopharyngeal carcinoma (NPC). We performed a case–control study between 217 patients with NPC and 360 healthy controls in a Chinese population using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay. A significantly increased risk of NPC was observed in the miR-34b/c rs4938723 CT/CC genotypes compared with the TT genotype (adjusted OR=1.44, 95 % CI 1.02–2.03, p=0.04), and also the C allele (adjusted OR=1.33, 95 % CI 1.04–1.70, p= 0.03). The gene–gene interaction of miR-34b/c rs4938723 and TP-53 Arg72-Pro showed that the combined genotypes L. Li : P. Bai : W. Deng : L. Zhang Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China L. Li : X. Deng : L. Zhang : L. Gao Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children’s Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China J. Wu Department of Head and Neck Oncology, Chongqing Cancer Hospital, Chongqing 400030, People’s Republic of China X. Sima Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China X. Deng : L. Zhang (*) : L. Gao (*) Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects, Ministry of Education, Chengdu, Sichuan 610041, People’s Republic of China e-mail: [email protected] e-mail: [email protected]

of rs4938723CT/CC and TP-53CG/CC increased the risk of NPC (rs4938723CT/CC+TP-53CG/CC vs. rs4938723 TT+ TP-53 CG/CC: OR=1.58, 95 % CI 1.04–2.42, p=0.03). These findings suggest that miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms may singly or collaboratively contribute to the risk of NPC. Keywords Nasopharyngeal carcinoma . miR-34b/c . TP-53 . Genetic polymorphism

Introduction Nasopharyngeal carcinoma (NPC) is the most common head and neck tumor originating in the nasopharynx. The incidence is up to 50/100,000 in South China and South Asia but is rare in the Western world (1/100,000) [1–3]. The morbidity of NPC is still high among Chinese people who have migrated to North America, suggesting that genetic factors contribute to the pathogenesis of NPC [4]. p53 is a regulator response to genotoxic stress, such as DNA damage, DNA repair, and cell cycle regulation, which tr