Dataset Information

Genetic variations in the SULF1 gene alter the risk of cervical cancer and precancerous lesions.

ABSTRACT: Human papillomavirus (HPV) infection alone is not sufficient to explain the development of cervical cancer. Genetic variants have been linked to the development of precancerous lesions and cervical cancer. In this study, we aimed to evaluate the association of 10 single nucleotide polymorphisms (SNPs) of the Fas cell surface death receptor (FAS), trinucleotide repeat containing 6C (TNRC6C), transmembrane channel like 8 (TMC8), DNA meiotic recombinase 1 (DMC1), deoxyuridine triphosphatase (DUT), sulfatase 1 (SULF1), 2'-5-oligoadenylate synthetase 3 (OAS3), general transcription factor IIH subunit 4 (GTF2H4) and interferon gamma (IFNG) genes with susceptibility to precancerous lesions and cervical cancer. In total, 608 female participants, consisting of 199 patients with persistent low-grade precancerous lesions (CIN1), 100 with high-grade precancerous lesions (CIN2/3), 17 patients with cervical cancer and 292 healthy controls, were enrolled in this study. SNPs were tested for associations with each of the above-mentioned cervical group lesions or when considering an overall patient group. A significant difference for rs4737999 was observed between the controls and the overall patient group considering the recessive mode of inheritance [odds ratio (OR), 0.48; 95% confidence interval (CI), 0.24-0.96; P=0.033]. This effect was even stronger on the risk of CIN1 lesions. Carriers of the rs4737999 AA genotype were almost 3-fold less likely of having low grade lesions compared to the other genotypes. On the whole, this study provides evidence of an influence of the SULF1 gene rs4737999 SNP in the development of precancerous lesions/cervical cancer.

SUBMITTER: Dardiotis E

PROVIDER: S-EPMC6096185 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Genetic variations in the SULF1 gene alter the risk of cervical cancer and precancerous lesions.

Dardiotis Efthimios E Siokas Vasileios V Garas Antonios A Paraskevaidis Evangelos E Kyrgiou Maria M Xiromerisiou Georgia G Deligeoroglou Efthimios E Galazios Georgios G Kontomanolis Emmanuel N EN Spandidos Demetrios A DA Tsatsakis Aristidis A Daponte Alexandros A

Oncology letters 20180706 3

Human papillomavirus (HPV) infection alone is not sufficient to explain the development of cervical cancer. Genetic variants have been linked to the development of precancerous lesions and cervical cancer. In this study, we aimed to evaluate the association of 10 single nucleotide polymorphisms (SNPs) of the Fas cell surface death receptor (FAS), trinucleotide repeat containing 6C (TNRC6C), transmembrane channel like 8 (TMC8), DNA meiotic recombinase 1 (DMC1), deoxyur ...[more]

PMID: 30127996

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Project description:OBJECTIVE:To screen potential plasma protein biomarkers for the progression of cervical precancerous lesions into cervical carcinoma and analyze their functions. METHODS:Plasma samples obtained from healthy control subjects, patients with low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), cervical cancer (CC), and patients with CC after treatment were enriched for low-abundance proteins for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The MS data of the samples were analyzed using Discoverer 2.2 software, and the differential proteins (peptide coverage ≥20%, unique peptides≥2) were screened by comparison of LSIL, HSIL and CC groups against the control group followed by verification using target proteomics technology. Protein function enrichment and coexpression analyses were carried out to explore the role of the differentially expressed proteins as potential biomarkers and their pathological mechanisms. RESULTS:Compared with the control group, both LSIL group and HSIL group showed 9 differential proteins; 5 differentially expressed proteins were identified in CC group. The proteins ORM2 and HPR showed obvious differential expressions in LSIL and HSIL groups compared with the control group, and could serve as potential biomarkers for the progression of cervical carcinoma. The expression of F9 increased consistently with the lesion progression from LSIL to HSIL and CC, suggesting its value as a potential biomarker for the progression of cervical cancer. CFI and AFM protein levels were obviously decreased in treated patients with CC compared with the patients before treatment, indicating their predictive value for the therapeutic efficacy. Protein function enrichment analysis showed that all these differentially expressed proteins were associated with the complement system and the coagulation cascades pathway. CONCLUSIONS:We identified 5 new protein biomarkers (F9, CFI, AFM, HPR, and ORM2) for cervical precancerous lesions and for prognostic evaluation of CC, and combined detection of these biomarkers may help in the evaluation of the development and progression of CC and also in improving the diagnostic sensitivity and specificity of cervical lesions.

Project description:Cervical cancer is the second most prevalent cancer among women in the developing countries including Ethiopia. Precancerous lesions can be developed and risk to the development of cervical cancer over time. Early identification of the precancerous lesion and its risk factor is paramount in preventing cervical cancer. However, the determinants of cervical precancerous lesions are not well documented in Ethiopia. Therefore, this study is conducted to determine factors associated with cervical precancerous lesion among women screened for cervical cancer.A hospital-based unmatched case-control study was conducted in selected health facilities in Addis Ababa from March to April 2016. Data were collected from 114 cases and 229 controls using an interviewer-administered questionnaire, entered to Epi Info version 7, and exported to SPSS version 20 for analysis. Odds ratios with its 95% confidence intervals and two-tailed P-value were calculated. Variables with P-value ? 0.2 in the bivariate analysis were included in the multivariate logistic regression model.Women aged 40-49 years had 2.4-fold higher odds of precancerous lesions compared to those aged 30-39 (Adjusted Odds Ratio = 2.4, 95% Confidence Interval: 1.27-4.54). Women having history of sexually transmitted infections were significantly associated with cervical precancerous lesion compared to their counterparts (Adjusted Odds Ratio = 3.20, 95% Confidence Interval: 1.26-8.10). Similarly, those women who had two or more lifetime sexual partners (Adjusted Odds Ratio = 2.17 95% Confidence Interval: 1.01-4.67), and women whose husbands had two or more lifetime sexual partners (Adjusted Odds Ratio = 3.03, 95% Confidence Interval: 1.25, 7.33) had higher odds of cervical precancerous lesions.Older age, history of multiple sexual partners and sexual transmitted infections were associated with increased risk of precancerous lesion. Therefore, women with higher risk of precancerous lesions should be encouraged to be screened more frequently for cervical cancer.

Dataset Information

Genetic variations in the SULF1 gene alter the risk of cervical cancer and precancerous lesions.

Publications

Genetic variations in the <i>SULF1</i> gene alter the risk of cervical cancer and precancerous lesions.

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