title: Genetic polymorphisms in the ITPKC gene and cervical squamous cell carcinoma risk.
abstract: Cervical cancer is caused primarily by infection with oncogenic types of human papillomavirus (HPV). However, HPV infection alone is not sufficient for the progression to cervical cancer. Host immunogenetic factors may involve in the development of this disease. Inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) is recently shown to act as a negative regulator of T-cell activation. We aim to study if polymorphisms in the ITPKC gene are associated with the risk of cervical cancer in Taiwanese women. ITPKC rs28493229 C/G, rs890934 G/T, rs2303723 C/T, and rs10420685 A/G polymorphisms were genotyped in a hospital-based study of 465 women with cervical squamous cell carcinoma (CSCC) and 800 age-matched healthy control women. The presence and genotypes of HPV in CSCC were determined. The frequency of G/G genotype and G allele of the ITPKC rs28493229 polymorphism was significantly higher in patients with CSCC compared with controls (OR = 1.81, 95 % CI 1.20-2.73, P = 0.005, P (c) = 0.02; OR = 1.70, 95 % CI 1.14-2.54, P = 0.008, P (c) = 0.03, respectively). No significant associations were found for other 3 polymorphisms. Haplotype analysis revealed the distribution of haplotype CGTA was significantly reduced in women with CSCC (OR = 0.59, 95 % CI 0.40-0.89, P = 0.01, P (c) = 0.04). In conclusion, we found the G/G genotype and G allele of the ITPKC rs28493229 polymorphism may contribute to the risk of CSCC in Taiwanese women. This finding provides new insights into the mechanisms of immune activation in cervical cancer.
authors.affiliation: Department of Gynecology and Obstetrics, Mackay Memorial Hospital, Taipei City, Taiwan.
authors.forename: Yuh-Cheng
authors.initials: YC
authors.lastname: Yang
authors.forename: Tzu-Yang
authors.initials: TY
authors.lastname: Chang
authors.forename: Tze-Chien
authors.initials: TC
authors.lastname: Chen
authors.forename: Shih-Chuan
authors.initials: SC
authors.lastname: Chang
authors.forename: Wei-Fang
authors.initials: WF
authors.lastname: Chen
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Chan
authors.forename: Wen-Shan
authors.initials: WS
authors.lastname: Lin
authors.forename: Fu-Ting
authors.initials: FT
authors.lastname: Wu
authors.forename: Yann-Jinn
authors.initials: YJ
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012306:Risk; D013624:Taiwan / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase