Dataset Information

Genetic variants of the dUTPase-encoding gene DUT increase HR-HPV infection rate and cervical squamous cell carcinoma risk.

ABSTRACT: Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is involved in the repair and prevention of uracil misincorporations into DNA. Maintenance of DNA integrity is critical for cancer prevention. Many studies have identified susceptibility loci and genetic variants in cervical cancer. The aim of this study was to explore the distribution frequency of six single nucleotide polymorphisms (SNPs) in the dUTPase-encoding gene DUT in a case-control study to identify the relationship between DUT genetic variants and cervical cancer susceptibility. Six DUT intronic SNPs (rs28381106, rs3784619, rs10851465, rs28381126, rs3784621 and rs11637235) were genotyped by mismatch amplification-PCR in 400 cervical squamous cell carcinomas (CSCCs), 400 precursor cervical intraepithelial neoplasia (CIN) III lesions and 1,200 normal controls. No correlations were found between four DUT SNPs (rs3784621, rs10851465, rs28381106 and rs28381126) and CIN III and CSCC risk. However, the homozygous GG allele of rs3784619 and TT allele of rs11637235 correlated significantly with increased risk of CIN III and CSCC (OR?=?2.29, 2.05; OR?=?3.15, 3.15, respectively). Individuals with the G allele or G carrier allele (AG?+?GG) at rs3784619 and with the T allele or T carrier allele (CT?+?TT) at rs11637235 were at higher risk for CIN III and CSCC (OR?=?1.26, 1.30; OR?=?1.41, 1.65, respectively). Similarly, in the human papillomavirus (HPV)-positive groups, we found that the homozygous GG alleles of rs3784619 and TT alleles of rs11637235 markedly increased the risk of CIN III and CSCC (OR?=?2.44, 2.71; OR?=?3.32, 4.04, respectively). When performing a stratified analysis of sexual and reproductive histories, we found that the GG genotype of rs3784619 had a particularly high level of enrichment in the group of patients with?>?one sexual partner in CIN III (P?=?0.043) and CSCC (P?=?0.007). Meanwhile, the TT genotype of rs11637235 was enriched for in the high risk HPV (HR-HPV)-positive cases of CIN III (P?=?0.033) and CSCC (P?=?0.022). Analysis of the haplotype between rs3784619 (A/G) and rs11637235 (C/T) revealed that the genotypes with AA-TT (OR?=?2.59), AG-TT (OR?=?2.29), GG-CC (OR?=?2.72), GG-CT (OR?=?3.01 (1.83-4.96)) were significantly associated with increased risk of CIN III. More notably, this risk was much greater for CSCC (AA-TT (OR?=?3.62), AG-TT (OR?=?5.08), GG-CC (OR?=?5.28), and GG-CT (OR?=?4.23). Additionally, most GG genotypes of rs3784619 were linkage GG-CT, while most TT genotypes of rs11637235 were linkage AA-TT. In conclusion, these findings suggested that the homozygous GG allele of rs3784619 and the TT allele of rs11637235 in the DUT gene significantly increased the risk of CIN III and CSCC. Most GG genotypes of rs3784619 and TT genotypes of rs11637235 were linkage GG-CT and AA-TT, respectively. The TT genotype of rs11637235 was enriched in the HR-HPV-positive cases. These two SNPs of the DUT gene can be early predictive biomarkers of CIN III and CSCC, and may be involved in HR HPV infection.

SUBMITTER: Ye F

PROVIDER: S-EPMC6345750 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Genetic variants of the dUTPase-encoding gene DUT increase HR-HPV infection rate and cervical squamous cell carcinoma risk.

Ye Feng F Wang Hanzhi H Liu Jia J Cheng Qi Q Chen Xiaojing X Chen Huaizeng H

Scientific reports 20190124 1

Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is involved in the repair and prevention of uracil misincorporations into DNA. Maintenance of DNA integrity is critical for cancer prevention. Many studies have identified susceptibility loci and genetic variants in cervical cancer. The aim of this study was to explore the distribution frequency of six single nucleotide polymorphisms (SNPs) in the dUTPase-encoding gene DUT in a case-control study to identify the relationship between DUT ...[more]

PMID: 30679536

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Project description:The Alinity m HR HPV assay (Alinity) is a novel human papillomavirus (HPV) assay that individually identifies genotypes HPV16, HPV18, and HPV45 while reporting on 11 other high-risk HPV (hrHPV) genotypes in two aggregates: HPV31/33/52/58 and HPV35/39/51/56/59/66/68. The clinical performance of Alinity for screening for cervical cancer was evaluated in population-based settings. For women aged ≥30 years, the clinical sensitivity (n = 68) and specificity (n = 3,077) for the detection of cervical intraepithelial neoplasia grade 2+ (CIN2+) of Alinity were 100.0% and 92.4%, respectively, and were not inferior to those of the Qiagen Digene Hybrid Capture 2 high-risk HPV DNA assay (hc2) (P = 0.0006 and P < 0.0001, respectively). The intralaboratory reproducibility and interlaboratory agreement of Alinity were 96.7% (kappa, 0.92) and 98.7% (kappa, 0.97), respectively. In the group ≥30 years of age, women who were baseline hrHPV negative had a lower risk for CIN2+ at 3 years using Alinity (0.04%) than those with a normal baseline cytology (0.65%) and had a risk comparable to that determined by the Abbott RealTime High Risk HPV assay (0.04%), hc2 (0.08%), or the Roche Cobas 4800 HPV assay (0.04%). High-risk HPV16/18 infection was associated with a significantly higher baseline and 3-year CIN2+ and CIN3+ risk than the absence of HPV16/18 or the presence of hrHPVs at the baseline (all P values were <0.05). The baseline CIN2+ risk was 8.8% for those with HPV31/33/52/58 infection and 2.5% for those with HPV35/39/51/56/59/66/68 infection, while the 3-year CIN2+ risk was 17.0% and 4.9%, respectively (relative risk, 3.4 [P = 0.03] and 3.5 [P = 0.003], respectively), suggesting that extended genotyping by Alinity may be valuable in improving patient risk stratification. Alinity fulfills international consensus guideline criteria for primary cervical cancer screening and can be considered clinically validated, demonstrating safety comparable to that of other clinically validated HPV tests.

Project description:Background:The efficacy of cervical cancer screening programs is dependent on the participation rate. To increase participation among women not attending cervical cancer screening, self-collected samples for detection of high-risk human papillomavirus (hr-HPV) may be an option.The aims of this study were: to investigate the response rate to sending a self-collected vaginal sample for hr-HPV mRNA detection to long-term non-attendees; the compliance with follow-up among women positive for HPV in the self-sample; the prevalence of cervical dysplasia (high grade squamous intraepithelial lesion (HSIL), atypical squamous cells that cannot exclude HSIL (ASC-H) or adenocarcinoma in situ (AIS)) or cancer among the responders; as well as to explore reasons for not returning a self-sample. Methods:A vaginal self-sampling kit was sent to 6023 women aged 30-70?years who had not provided a cervical screening sample for ?7?years in the Region of Skåne, Sweden in November and December 2017. The self-sample was analyzed by Aptima HPV mRNA assay (Hologic). All vaginal self-samples returned no later than May 31, 2018 were included in the study. Follow-up of the results was registered until January 31, 2019 with a follow-up time varying between eight to 14?months. Women positive for hr-HPV mRNA were invited for a follow-up examination. This examination consisted of a cervical sample for cytological analysis and renewed Aptima HPV mRNA testing. Two hundred thirty-five women who had not returned the self-sample were randomly selected for telephone interviews, in order to explore their reasons. Results:The response rate for the self-collected vaginal hr-HPV sample was 13.2% [(797/6023), 95% CI 12.4-14.1%] and 9.9% [(79/796), 95% CI 7.9-12.2%] were positive for hr-HPV mRNA. The prevalence of severe dysplasia or cancer in the whole group of responders was 1.3% [(10/796), 95% CI 0.6-2.3%], with a cervical cancer prevalence of 0.4% [(3/796), 95% CI 0.1-1.1%]. Only 27 women participated in the telephone interviews, no particular reason for not returning self-samples was observed. Conclusions:Self-collected vaginal hr-HPV samples increased participation in the cervical cancer screening among long-term non-attendees. The prevalence of cervical cancer was almost seven times higher for long-term non-attendees than in the organized screening population.

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Dataset Information

Genetic variants of the dUTPase-encoding gene DUT increase HR-HPV infection rate and cervical squamous cell carcinoma risk.

Publications

Genetic variants of the dUTPase-encoding gene DUT increase HR-HPV infection rate and cervical squamous cell carcinoma risk.

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