Cervical Cancer In Chinese Population Research Articles

Association of p73 G4C14-A4T14 and p53 codon 72 polymorphism with cervical cancer in Chinese population.

Cervical cancer is known to be the fourth most common cancer among women globally. In various factors, genetic factors have been considered as one major risk factor for cervical cancer. The research of genetic susceptibility to cervical cancer can be greatly helpful in studying the complex mechanism. This study was conducted to identify whether polymorphic variants of p73 G4C14-A4T14 and tumor protein p53 (p53) codon 72, either independently or jointly, might be associated with the risk of cervical cancer. The genotypes of p73 G4C14-A4T14 and p53 codon 72 polymorphisms of peripheral blood DNA from 190 cervical cancer patients and 210 controls were investigated using polymerase chain reaction with confronting two-pair primers and polymerase chain reaction-restriction fragment length polymorphism, respectively. The frequency of p73 G4C14-A4T14 AT/AT (P = 0.013) or p53 codon 72 GG (P = 0.026) genotype was associated with an increased risk of cervical cancer by comparing with the p73 G4C14-A4T14 GC/GC or p53 codon 72 CC genotype, respectively. In addition, the interaction between the p73 G4C14-A4T14 and p53 codon 72 polymorphisms increased the risk of cervical cancer in a multiply manner, with the odds ratio being 3.692 (95% confidence interval =2.106-6.473) for subjects carrying both p73 G4C14-A4T14 GC/AT+AT/AT and p53 codon 72 GG genotypes. These results suggest that there is a statistical difference between p73 and p53 gene polymorphism and the risk of cervical cancer in Chinese women, and there is a potential gene-gene interaction in the incidence of cervical cancer.

Abstract 3444: Analysis of human papillomavirus 16 variants and risk for cervical cancer in Chinese population

Abstract HPV16 is the most carcinogenic HPV type, but only a minority of HPV16 infections progress to cancer. Intratype genetic variants of HPV16 have been suggested to confer differential carcinogenicity. To investigate risk implications of HPV16 variants among Chinese women, a case-control study was conducted with 298 cervical cancer patients and 85 controls (all HPV16-positive). HPV16 isolates were predominantly of the A variant lineage, and variants of A4 (previously named “Asian”) sublineage were common. A4/Asian variants were significantly associated with increased risk of cervical cancer compared to A1-3 (OR = 1.72, 95% CI = 1.04-2.85). Furthermore, a meta-analysis including 703 cases and 323 controls from East Asia confirmed the association (OR = 2.82, 95% CI = 1.44-5.52). In conclusion, A4 variants appear to predict higher risk of cervical cancer among HPV16-positive women, which may provide clues to the genetic basis of differences in the carcinogenicity of HPV16 variants. Citation Format: Dong Hang, Yin Yin, Jing Han, Jie Jiang, Hongxia Ma, Shuanghua Xie, Xiaoshuang Feng, Kai Zhang, Zhibin Hu, Shen Hongbing, Gary M. Clifford, Min Dai, Ni Li. Analysis of human papillomavirus 16 variants and risk for cervical cancer in Chinese population. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3444.

Analysis of human papillomavirus 16 variants and risk for cervical cancer in Chinese population

HPV16 is the most carcinogenic HPV type, but only a minority of HPV16 infections progress to cancer. Intratype genetic variants of HPV16 have been suggested to confer differential carcinogenicity. To investigate risk implications of HPV16 variants among Chinese women, a case-control study was conducted with 298 cervical cancer patients and 85 controls (all HPV16-positive). HPV16 isolates were predominantly of the A variant lineage, and variants of A4 (previously named “Asian”) sublineage were common. A4/Asian variants were significantly associated with increased risk of cervical cancer compared to A1–3 (OR=1.72, 95% CI=1.04–2.85). Furthermore, a meta-analysis including 703 cases and 323 controls from East Asia confirmed the association (OR=2.82, 95% CI=1.44–5.52). In conclusion, A4 variants appear to predict higher risk of cervical cancer among HPV16-positive women, which may provide clues to the genetic basis of differences in the carcinogenicity of HPV16 variants.

A Systematic Literature Review on Risk Factors for Cervical Cancer in Chinese Population.

A Systematic Literature Review on Risk Factors for Cervical Cancer in Chinese Population.

Meta-Analysis on the Relationship between HLA-DRBl Gene Polymorphism and Cervical Cancer in Chinese Population

AimTo determine the association between HLA-DRB1 haplotypes and risk of cervical cancer in unselected and samples from Chinese ethnicities.MethodsA comprehensive search for articles from their inception to April 1st, 2013 was conducted from PubMed, Medline, Elsevier Science, Springer Link, Cochrane Library database, China biology medical literature database (CBM),China National Knowledge Infrastructure (CNKI),VIP,and Chinese literature database(Wang fang). A total of 1596 patients with cervical cancer and 2048 controls from the 12 studies on the relationship between gene polymorphism of HLA-DRB l and cervical cancer were performed and data were analyzed and processed using Review Manager 5.0 and Stata 11.0.ResultsAmong the 13 family alleles, two (DRB1*03 and DRB1*08) were found to be negatively associated with cervical cancer in all studies or in Uighur subgroups, and two (DRB1*10 and DRB1*15) were positively associated with in all studies or in Uighur subgroups. Among the 25 specific alleles, six (DRB1*0301, *0403,*0404, *0803, *1312 and *1502) were associated with an increased risk cervical cancer in all studies. No significant association was established for other HLA-DRB1 family alleles and specific alleles. Ethnicity partially explained the race influence of DRB1*12, DRB1*14, DRB1*0301, DRB1*0403, DRB1*0404, DRB1*0803, DRB1*1312 and DRB1*1502 phenotypes.ConclusionOur results support the hypothesis that the HLA-DRB1 family alleles and specific alleles might influence the susceptibility or resistance to cervical cancer, suggesting that immune regulation may play a key role in this disease, although further investigations are still needed.

Meta-analysis of the cytotoxic T-lymphocyte antigen 4 gene +6230G/A polymorphism and cancer risk

Cytotoxic T-lymphocyte antigen-4 (CTLA4, CD152) is one of the most fundamental immunosuppressive cytokines that inhibits T-cell activation and terminates the T-cell response by blocking signals stimulated via CD28. A number of studies have assessed the association between CTLA-4 +6230G/A polymorphism and cancer risk. However, the results remain controversial. In the present study, we performed a meta-analysis to derive a more precise estimation of the relationship. A comprehensive literature search was performed using the PubMed database for relevant articles published (updated to November 21, 2013). Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of the association. A total of 13 articles with 14 studies were selected for this meta-analysis, including 4,489 cases and 4,715 controls. Combined analysis revealed no associations between CTLA-4 +6230G/A polymorphism and cancer risk. However, in stratified analysis by cancer type, we found that CTLA-4 +6230G/A polymorphism was associated with the risk of breast cancer (AA vs. AG + GG: OR = 0.77, 95 % CI 0.60-0.97, P = 0.03; AA vs. GG: OR = 0.66, 95 % CI 0.46-0.95, P = 0.02) and cervical cancer (AA vs. AG + GG: OR = 0.56, 95 % CI 0.42-0.75, P < 0.01). Additionally, in subgroup analysis based on ethnicity, significant association was also found between the CTLA-4 +6230G/A polymorphism and cancer risk in the Asian population (AA vs. AG + GG: OR = 0.71, 95 % CI 0.59-0.84, P < 0.01). This meta-analysis indicates that CTLA-4 +6230G/A polymorphism may be associated with a decreased risk of breast cancer and cervical cancer in Chinese population.

The Association Between -1304T&gt;G Polymorphism in the Promoter of Mitogen-Activated Protein Kinase Kinase 4 Gene and the Risk of Cervical Cancer in Chinese Population

Mitogen-activated protein kinase kinase 4 (MKK4) is a critical mediator of stress-activated protein kinase signals that regulate apoptosis, inflammations, and tumorigenesis. Several polymorphisms have been identified in the MKK4 gene. We hypothesized that genetic variants in the MKK4 promoter may alter its functions and thus cancer risk. In the current, hospital-based case-control study of 471 cervical cancer cases and 600 sex and age frequency-matched cancer-free controls in an Eastern Chinese population, we genotyped two common polymorphisms in the MKK4 promoter region (-1304T>G, rs3826392 and -1044A>T, rs3809728)c and assessed their associations with the risk of cervical cancer. We found that compared with the most common -1304TT genotype, carriers of -1304G variant genotypes had a significantly decreased risk of cervical cancer [odds ratio (OR) = 0.71; 95% confidence interval (CI) = 0.53-0.92 for TG, and OR = 0.52; 95%CI = 0.30-0.91 for GG] in an allele dose-response manner (adjusted P(trend) = 0.004). Moreover, the luciferase assay showed that the G allele in the promoter significantly increased the transcription activity of the MKK4 gene in vitro and that the MKK4 mRNA expression levels of the G variant carriers was significantly higher in tumor tissues than those of the -1304TT genotype. However, no significant association was observed between the -1044A>T polymorphism and risk of cervical cancer. Our data suggest that the functional -1304G variant in the MKK4 promoter contributes to a decreased risk of cervical cancer by increasing the promoter activity and that the G variant may be a marker for susceptibility to cervical cancer.

Functional polymorphism in the EpCAM gene is associated with occurrence and advanced disease status of cervical cancer in Chinese population

The epithelial cell adhesion molecule (EpCAM) was originally identified as a tumor associated antigen, attributable to its high expression on rapidly proliferating tumors of epithelial origin. EpCAM plays vital roles in carcinogenesis, tumor progression and metastasis in most tumors. A non-synonymous polymorphism (rs1126497 C/T) was found in exon 3 of EpCAM, which cause a transition from 115 Met to 115 Thr. Another polymorphism (rs1421 A/G) in the 3'UTR causes loss of has-miR-1183 binding. We performed a multiple independent case-control analysis to assess the association between EpCAM genotypes and cervical cancer risk. Genotyping a total of 518 patients with cervical cancer and 723 control subjects in a Chinese population, we observed that the variant EpCAM genotypes (rs1126497 CT, and TT) were associated with substantially increased risk of cervical cancer. Compared with the rs1126497 CC genotype, CT genotype had a significantly increased risk of cervical cancer (Crude OR = 1.70; 95% CI = 1.33-2.20; adjusted OR = 1.72; 95% CI = 1.33-2.22), the TT carriers had a further increased risk of cervical cancer (Crude OR = 1.94; 95% CI = 1.01-3.72; adjusted OR = 1.96; 95%CI = 1.01-3.81), and there was a trend for an allele dose effect on risk of cervical cancer (P < 0.001). Moreover, the allele T increases the risk for invasive disease or metastatic disease, compared with C allele. However, there exists no significant difference in genotype frequencies of rs1421 A/G site between cases and controls (P = 0.798). These findings suggest that rs1126497 C/T polymorphism in EpCAM may be a genetic modifier for developing cervical cancer.

CCND1 rs9344 polymorphisms are associated with the genetic susceptibility to cervical cancer in Chinese population

Cyclin D1, with a common G/A polymorphism in rs9344, is an essential regulator of the G1 phase in cell cycles and plays an important role in several tumor types, and the homology of cyclin D1 with human papillomavirus (HPV)-16 E7 brought our attention to CCND1 gene in cervical cancer. A total of 738 native Chinese subjects consist of 327 cases and 411 controls were enrolled in this study. CCND1 genotyping was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and partially verified by sequencing of genomic DNA and cDNA. The transcription of cyclin D1 mRNA isoforms was analyzed by quantitative PCR; expression of protein isoforms by immunohistochemistry and Western blotting. We observed that the AA genotype had decreased risk of developing cervical cancer (odds ratio [OR] = 0.332; 95% confidence interval [CI] = 0.113-0.978; P = 0.045). The two mRNA isoforms were both transcripted from A and G allele. Transcript b decreased in squamous cell carcinoma of the uterine cervix (SCCUC) group (P = 0.004), especially poorly differentiated group (P = 0.004), and in G allele group of normal subjects (P = 0.001). In immunohistochemistry analysis, cyclins D1, D1a, and D1b failed to correlate with cervical cancer (P = 0.808, 0.445, and 0.095). However, cyclin D1b was downregulated in SCCUC group analyzed by Western blotting (P = 0.039). This study indicates that CCND1 rs9344 polymorphisms confer host susceptibility to cervical cancer. A allele possesses a relative protective effect probably through the cyclin D1b's inhibition on HPV carcinogenesis.

Association of CD28 gene polymorphism with cervical cancer risk in a Chinese population

Human papilloma virus plays a causal role in cervical carcinogenesis. However, only a small portion of infected individuals develop cervical cancer. Host genetic factors may confer susceptibility to this disease. CD28 participates in the maintenance of immune homeostasis as an important positive co-stimulatory molecule. Allelic variation of immuno-modulatory genes may be associated with alteration in immune function. This study investigated the associations between CD28 IVS3 +17T>C polymorphism and risk of cervical cancer in the Chinese population. Genotypes of CD28 polymorphism were detected in 619 cases with primary cervical cancer and in 985 normal controls. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression. A higher frequency of CD28 +17TC heterozygote was determined in patients in comparison with controls (19.4% versus 12.5%). Subjects carrying at least one CD28 IVS3 +17 C allele (TC or CC genotype) had increased risk of cervical cancer (OR=1.66, 95% CI=1.27-2.17). This study suggests that the CD28 IVS3 +17T>C polymorphism might be genetic susceptibility factor for cervical cancer in Chinese population.

Polymorphic amino acids at codons 9 and 37 of HLA‐DQB1 alleles may confer susceptibility to cervical cancer among Chinese women

Cervical cancer is strongly associated with the infection by oncogenic forms of human papillomavirus (HPV). Although most women are able to clear HPV infection, some develop persistent infections that may lead to cancer, implying genetic susceptibility factors for malignant progression. To verify whether HLA class II DQB1 polymorphism is related to cervical cancer in Chinese population, HLA-DQB typing was carried out by PCR-SBT for 258 patients with cervical cancer and 284 healthy controls, and the allele frequencies were calculated. In this study, HLA-DQB1*060101 and DQB1*0602 alleles were significantly higher in the HPV16 infected patients with cervical cancer compared with healthy controls (chi(2) = 31.7452, p < 0.0001; chi(2) = 12.7838, p(c) = 0.0066), but DQB1*050201 allele was significantly lower (chi(2) = 26.2187, p < 0.0001). This result indicates that HLA-DQB1*060101 and DQB1*0602 may confer susceptibility to cervical cancer, and DQB1*050201 may contribute to the resistance to the development of cervical cancer among Chinese women. Sequence analysis reveals that DQB1*060101 allele encodes Leu at position 9 and Asp at position 37, unique to the susceptibility to cervical cancer, whereas the other DQB1 alleles encode Phe or Tyr and Ile or Tyr at the same two positions, respectively. This finding implies that polymorphic amino acids at the putative antigen binding residues 9 and 37 of HLA-DQB1 alleles may play an important role in the development of cervical cancer.