ITPR3 gene haplotype is associated with cervical squamous cell carcinoma risk in Taiwanese women

// Yuh-Cheng Yang 1, 4, * , Tzu-Yang Chang 3, * , Tze-Chien Chen 1 , Wen-Shan Lin 3 , Shih-Chuan Chang 3 , Yann-Jinn Lee 2, 3, 5, 6, 7 1 Department of Gynecology and Obstetrics, MacKay Memorial Hospital, Taipei City 2 Department of Pediatric Endocrinology, MacKay Children’s Hospital, Taipei City 3 Department of Medical Research, MacKay Memorial Hospital, New Taipei City 4 Department of Gynecology and Obstetrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan 5 Departments of Gynecology and Obstetrics, Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 6 Institute of Biomedical Sciences Mackay Medical College, New Taipei City, Taiwan 7 Department of Medicine, Mackay Medical College, New Taipei City, Taiwan * These authors contributed equally to this work. Correspondence to: Yann-Jinn Lee, email: yannlee@mmh.org.tw , kylechang@mmh.org.tw Keywords: cervical cancer, HPV, immunity, ITPR3, polymorphism Received: June 15, 2016 Accepted: December 15, 2016 Published: December 28, 2016 ABSTRACT 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.