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.
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ABSTRACT: Most human papillomavirus (HPV)-associated cervical intraepithelial neoplasia(CIN) lesions in normal women regress spontaneously, but a small number persist and may progress to invasive cancer. To evaluate the role of immunity to HPV and the outcome of CIN and associated HPV infection, we examined cell-mediated immune (CMI) responses to HPV 16 E6 and E7 peptides. One hundred thirty-six women with biopsy-confirmed CIN I or CIN II were followed for 1 year at 3 month intervals. Study subjects were 58% Hispanic, 36% African American, and 6% of other ethnicity, and were attending a municipal hospital colposcopy clinic. At each visit, cervical cytology and cervicovaginal lavage for HPV detection and typing was done, and blood was obtained for immunological studies. Lymphoproliferative CMI responses to HPV 16 E6 and E7 peptides were tested. An end point biopsy was done after the 1-year follow-up. The association between CMI responses to specific peptides and the outcome of disease was evaluated. CMI responses to E7 peptide (37-54) correlated significantly with regression of disease and with resolution of viral infection within 12 months. The protective effects of CMI to this peptide were not HPV type-specific. CMI responses to several other peptides also showed an association with regression, although not significant at present sample size. E7 peptide 37-54 contains one or more human T-cell epitopes. Identification and mapping of "protective" epitopes in the HPV E6 and E7 proteins could lead to the development of immunological assays to determine the risk of CIN and the development of immunotherapeutic protocols for the management of premalignant and malignant HPV-associated neoplasia and, ultimately, for the prevention of cancer.Cancer Epidemiology Biomarkers & Prevention 06/2002; 11(5):483-8. · 4.56 Impact Factor
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ABSTRACT: We examined cervical cancer incidence before and after nationwide cervical cancer screening was initiated in Taiwan in mid-1995. The invasive cancer incidence decreased by 47.8% during 1995-2006. The carcinoma in situ incidence increased 1.7-fold during 1995-2000, and decreased by 19.6% during 2000-2006. The Taiwan national programme has significantly decreased invasive cervical cancer.British Journal of Cancer 07/2009; 101(1):174-7. · 5.08 Impact Factor
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ABSTRACT: Cervical cancer (CC) is closely associated with the human papillomavirus (HPV). Although most patients are able to clear the infection over time, some eventually develop cancer, suggesting the existence of other factors that determine malignant progression. Such factors may include genetic susceptibility. To determine whether human leukocyte antigen (HLA) class II is related to CC among Han race population in the Guangdong region of China, HLA class II typing were carried out by polymerase chain reaction in 126 patients with CC and 88 selected controls. The allele and haplotype frequencies in both the study and control groups were calculated. The occurrence of DPB1 *1301 [odds ratio (OR), 2.66; 95% confidence interval (CI), 1.12-6.29], DPB1 *0202 (OR, 3.65; CI, 1.04-12.80), DQB1 *030302(OR, 1.85; CI, 1.04-3.27), and DQB1 *050301(OR, 3.94; CI, 1.48-10.46) alleles were more common in the study group than control. This suggests that these alleles may confer susceptibility to CC in the Guangdong Province. In a similar fashion, the occurrence of DRB1 *13-DQB1 *06 (OR, 0.17; 95% CI, 0.04-0.80) haplotype was significantly lower in the study patients compared with the controls and may confer a decreased risk of CC among Han race population in the Guangdong Province of China.Cancer genetics and cytogenetics 01/2009; 187(2):95-100. · 1.54 Impact Factor