Cervical precancerous lesions – chromosomal instability in peripheral blood lymphocytes in relation to lesion stage, age and smoking habits

Milošević-Djordjević, Olivera; Stošić, Ivana; Grujičić, Darko; Banković, Dragić; Arsenijevic, Slobodan

doi:10.1111/j.1600-0412.2011.01230.x

Cited by 12 publications

(6 citation statements)

References 33 publications

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“…Moreover, with more than half a million new cases and 275,000 deaths per year, cervical cancer continues to constitute a major public health problem and particularly affects young women in developing countries [2, 3]. Cervical cancer develops through a multistep process, with three cervical intraepithelial neoplasia grades, 1 to 3 (CIN1-3) [4]. However, it will take several years, even decades, from pre-cancer to invasive cervical cancer, which offers us many opportunities for intervention.…”

Section: Introductionmentioning

confidence: 99%

Interaction between susceptibility loci in cGAS-STING pathway, MHC gene and HPV infection on the risk of cervical precancerous lesions in Chinese population

Xiao

Huang

et al. 2016

Oncotarget

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Human papillomavirus (HPV) infection is a definite risk factor for cervical cancer. Nevertheless, only some infected individuals actually develop cervical cancer. The cGAS-STING pathway in innate immunity plays an important role in protecting against HPV infection. Chen et al. described that the rs2516448 SNP in the MHC locus may affect susceptibility to cervical cancer, a finding that we attempted to replicate in a Chinese population. To investigate the effects of cGAS, STING and MHC polymorphisms on susceptibility to cervical precancerous lesions, 9 SNPs were analyzed in 164 cervical precancerous lesion cases and 428 controls. Gene-gene and gene-environment interactions were also evaluated. We found a significantly decreased risk of cervical precancerous lesions for the GG genotype of rs311678 in the cGAS gene (ORadjusted = 0.40, 95% CI: 0.16−0.98). Moreover, MDR analysis identified a significant three-locus interaction model, involving HPV infection, age at menarche and rs311678 in cGAS. Additionally, a significant antagonistic interaction between HPV infection and rs311678 was found on an additive scale. In conclusion, our results indicate that the rs311678 polymorphism in the cGAS gene confers genetic susceptibility to cervical precancerous lesions. Moreover, the three-way gene-environment interactions further demonstrate that the rs311678 polymorphism in cGAS can significantly decrease the risk of HPV infection and the elder at menarche.

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Section: Introductionmentioning

confidence: 99%

Interaction between susceptibility loci in cGAS-STING pathway, MHC gene and HPV infection on the risk of cervical precancerous lesions in Chinese population

Xiao

Huang

et al. 2016

Oncotarget

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“…Werkmeister et al [26] reported that some genotoxic secretions are released by tumor tissues into the bloodstream, which might cause the significant increase in DNA damage [27], sister chromatid exchanges [13,28,29], micronuclei [12,30–32], and chromosome aberrations (chromatid-type, chromosome-type, and asymmetric aberrations) [32] observed in leukocytes.…”

Section: Discussionmentioning

confidence: 99%

5-bp Classical Satellite DNA Loci from Chromosome-1 Instability in Cervical Neoplasia Detected by DNA Breakage Detection/Fluorescence in Situ Hybridization (DBD-FISH)

Cortés‐Gutiérrez

Ortíz-Hernández

Dávila-Rodríguez

et al. 2013

IJMS

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We aimed to evaluate the association between the progressive stages of cervical neoplasia and DNA damage in 5-bp classical satellite DNA sequences from chromosome-1 in cervical epithelium and in peripheral blood lymphocytes using DNA breakage detection/fluorescence in situ hybridization (DBD-FISH). A hospital-based unmatched case-control study was conducted in 2011 with a sample of 30 women grouped according to disease stage and selected according to histological diagnosis; 10 with low-grade squamous intraepithelial lesions (LG-SIL), 10 with high-grade SIL (HG-SIL), and 10 with no cervical lesions, from the Unidad Medica de Alta Especialidad of The Mexican Social Security Institute, IMSS, Mexico. Specific chromosome damage levels in 5-bp classical satellite DNA sequences from chromosome-1 were evaluated in cervical epithelium and peripheral blood lymphocytes using the DBD-FISH technique. Whole-genome DNA hybridization was used as a reference for the level of damage. Results of Kruskal-Wallis test showed a significant increase according to neoplastic development in both tissues. The instability of 5-bp classical satellite DNA sequences from chromosome-1 was evidenced using chromosome-orientation FISH. In conclusion, we suggest that the progression to malignant transformation involves an increase in the instability of 5-bp classical satellite DNA sequences from chromosome-1.

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“…Cervical cancer develops through a multistep process, with three cervical intraepithelial neoplasia grades, 1 to 3 (CIN1-3; ref. 4). The transition from CIN to invasive cancer will take several years, even decades, which offers us many opportunities for intervention and only a minority of the infected individuals go on to develop invasive cervical cancer (5).…”

Section: Introductionmentioning

confidence: 99%

Interaction Between Susceptibility Loci in MAVS and TRAF3 Genes, and High-risk HPV Infection on the Risk of Cervical Precancerous Lesions in Chinese Population

Xiao¹,

Liu²,

Wen³

et al. 2019

Cancer Prevention Research

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Persistent high-risk HPV infection is considered as a major cause of cervical cancer. Nevertheless, only some infected individuals actually develop cervical cancer. The RIG-I pathway in innate immunity plays an important role in antivirus response. Here, we hypothesized that altered function of mitochondrial antiviral signaling protein (MAVS) and mitochondrial TNF receptorassociated factor 3(TRAF3), key molecules downstream of the viral sensors RIG-I, may impair their ability of clearing HPV and thereby influence the risk for cervical precancerous lesions. To investigate the effects of MAVS and TRAF3 polymorphisms on susceptibility to cervical precancerous lesions, 8 SNPs were analyzed in 164 cervical precancerous lesion cases and 428 controls. Gene-environment interactions were also calculated. We found that CA genotype of rs6052130 in MAVS gene were at 1.48 times higher risk of developing cervical precancerous lesion than individuals with CC genotype (CA vs. CC: OR adjusted ¼ 1.48, 95% CI, 1.02-2.16). In addition, a significant synergetic interaction between high-risk HPV infection and rs6052130 was found on an additive scale. A significantly decreased risk of cervical precancerous lesions for the TC genotype of rs12435483 in the TRAF3 gene (OR adjusted ¼ 0.67, 95% CI, 0.45-0.98) was also found. Moreover, MDR analysis identified a significant three-locus interaction model, involving high-risk HPV infection, TRAF3 rs12435483 and number of full-term pregnancies. Our results indicate that the MAVS rs6052130 and TRAF3 rs12435483 confer genetic susceptibility to cervical precancerous lesions. Moreover, MAVS rs6052130-mutant individuals have an increased vulnerability to high-risk HPV-induced cervical precancerous lesions.

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Cervical precancerous lesions – chromosomal instability in peripheral blood lymphocytes in relation to lesion stage, age and smoking habits

Abstract: The results suggest that MN frequency in PBL of patients with cervical precancerous lesions corresponds to an increase of chromosomal damage, irrespective of smoking habits, miscarriages, abortions and lesion stages.

Cited by 12 publications

References 33 publications

Interaction between susceptibility loci in cGAS-STING pathway, MHC gene and HPV infection on the risk of cervical precancerous lesions in Chinese population

Interaction between susceptibility loci in cGAS-STING pathway, MHC gene and HPV infection on the risk of cervical precancerous lesions in Chinese population

5-bp Classical Satellite DNA Loci from Chromosome-1 Instability in Cervical Neoplasia Detected by DNA Breakage Detection/Fluorescence in Situ Hybridization (DBD-FISH)

Interaction Between Susceptibility Loci in MAVS and TRAF3 Genes, and High-risk HPV Infection on the Risk of Cervical Precancerous Lesions in Chinese Population

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