ITPR3 gene haplotype is associated with cervical squamous cell carcinoma risk in Taiwanese women
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Yuh-Cheng Yang1,4,*, Tzu-Yang Chang3,*, Tze-Chien Chen1, Wen-Shan Lin3, Shih-Chuan Chang3, Yann-Jinn Lee2,3,5,6,7
1Department of Gynecology and Obstetrics, MacKay Memorial Hospital, Taipei City
2Department of Pediatric Endocrinology, MacKay Children’s Hospital, Taipei City
3Department of Medical Research, MacKay Memorial Hospital, New Taipei City
4Department of Gynecology and Obstetrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan
5Departments of Gynecology and Obstetrics, Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei City
6Institute of Biomedical Sciences Mackay Medical College, New Taipei City, Taiwan
7Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
*These authors contributed equally to this work.
Yann-Jinn Lee, email: [email protected], [email protected]
Keywords: cervical cancer, HPV, immunity, ITPR3, polymorphism
Received: June 15, 2016 Accepted: December 15, 2016 Published: December 28, 2016
Host immunogenetic background plays an important role in human papillomavirus (HPV) infection and cervical cancer development. Inositol 1,4,5-triphosphate receptor type 3 (ITPR3) is essential for both immune activation and cancer pathogenesis. We aim to investigate if ITPR3 genetic polymorphisms are associated with the risk of cervical cancer in Taiwanese women. ITPR3 rs3748079 A/G and rs2229634 C/T polymorphisms were genotyped in a hospital-based study of 462 women with cervical squamous cell carcinoma (CSCC) and 921 age-matched healthy control women. The presence and genotypes of HPV in CSCC was determined. No significant association of individual ITPR3 variants were found among controls, CSCC, and HPV-16 positive CSCC. However, we found a significant association of haplotype AT between CSCC and controls (OR = 2.28, 95% CI 1.31–3.97, P = 2.83 × 10−3) and the OR increased further in CSCC patients infected with HPV-16 (OR = 2.89, 95% CI 1.55–5.37, P = 4.54 × 10−4). The linkage disequilibrium analysis demonstrated that ITPR3 association with CSCC was independent of HLA-DRB1 alleles. In conclusion, these findings suggest that AT haplotype in the ITPR3 gene may serve as a potential marker for genetic susceptibility to CSCC.
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