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.
Highlights
Cervical cancer is the fourth most common cancer in women worldwide
We aim to investigate if ITPR3 genetic polymorphisms are associated with the risk of cervical cancer in Taiwanese women
We did not find any significant differences in the genotype and allele frequencies for the 2 ITPR3 single nucleotide polymorphisms (SNPs) between cervical squamous cell carcinoma (CSCC) patients and controls (Tables 1 and 2)
Summary
Cervical cancer is the fourth most common cancer in women worldwide. In Taiwan, cervical cancer poses a major public health concern, with nearly 2700 women were diagnosed with cervical cancer each year [1]. Infection with oncogenic human papillomavirus (HPV) is necessary for the development of cervical cancer [2]. The majority of women infected with HPV do not progress into cervical cancer, suggesting that other factors are required for the cancer to develop. The inositol 1,4,5-triphosphate receptor type 3 (ITPR3), an intracellular Ca2+ release channel on the endoplasmic reticulum membrane, is responsive to the binding of a second messenger inositol 1,4,5-triphosphate (IP3) [3]. IP3 is phosphorylated to become IP4 by inositol 1,4,5-triphosphate 3-kinase C (ITPKC) and negatively regulates T-cell receptor signal transduction [4]. A study reported by our group revealed that a genetic variant www.impactjournals.com/oncotarget
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