scholarly journals Lead (Pb) exposure from outdoor air pollution: a potential risk factor for cervical intraepithelial neoplasia related to HPV genotypes

Author(s):  
Ji Zhang ◽  
Seyed Ali Nazeri ◽  
Amir Sohrabi

AbstractHuman papillomavirus genotypes (HPVs) have been confirmed to be the major cause of cervical intraepithelial neoplasia (CIN) that remains to be one of the most common women cancers around the world. It seems other risk factors have synergistic effects on cervical cancer occurrence including smoking, dietary pattern, sexual behavior, ethnicity, epigenetics, and environmental hazardous materials. Our study characterized the potential cancerous role of lead (Pb) as a common toxic environmental pollutant agent on CIN outcomes. Lead concentration was quantified using an atomic absorption spectrometer in liquid-based cytology specimens of 40 CIN-HPV positive subjects, 50 HPV infected non-cancerous cases, and 43 non-HPV infected/non-cancerous women. Pb concentration was 5.5 (4.7–6.4) μg/dL, 4.7 (4.2–8.7) μg/dL, and 4.7 (4.5–5.4) μg/dL in the CIN-HPV positive group, HPV infected non-cancerous cases, and non-HPV infected/non-cancerous group, respectively. The results showed higher Pb concentration is associated with higher risk for cervical malignancy in comparison with non-HPV infected/non-cancerous subjects, after controlling for age effect (aOR = 4.55, 95% CI: 1.55–15.07, P < 0.01). Our finding suggested a direct significant association between Pb accumulation and CIN existence. The consequences need to be further validated by including more relevant risk factors and controlling the confounders for better understating of Pb impact from outdoor air pollution on cervical cancer progression.

2021 ◽  
Author(s):  
Ji Zhang ◽  
Seyed Ali Nazeri ◽  
Amir Sohrabi

Abstract Human papillomavirus genotypes (HPVs) have been confirmed to be the major cause for Cervical Intraepithelial Neoplasia (CIN) that remains to be one of the most common women cancer around the world. It seems other risk factors connect to the occurrence of cervical cancer include smoking, dietary pattern, sexual behaviour, ethnicity, epigenetics and environmental hazardous materials. Our study characterized the potential cancerous role of Lead (Pb) as a common toxic environmental pollutant agent on CIN outcomes. The concentration of Pb was quantified using atomic absorption spectrometer in the liquid based cytology specimens of 40 CIN subjects, 50 HPV infected-non cancerous cases and 43 non-HPV infection/non-cancerous women. The Pb concentration was 5.5 (4.7–6.4) µg/dL, 4.7 (4.2–8.7) µg/dL and 4.7 (4.5–5.4) µg/dL in CIN group, control group with HPV infection and non-HPV/non-cancerous group, respectively. The results showed higher Pb concentration is associated with higher risk for cervical malignancy in comparison with non-HPV/non-cancerous subjects, after controlling for age effect (aOR = 4.55, 95% CI: 1.55–15.07, P < 0.01). Our finding suggested a direct significant association between Pb accumulation and CINs existence related to HPV infection. The consequence needs to be further validated by controlling the confounders to better understanding of Pb impact from outdoor air pollution on cervical cancer.


2014 ◽  
Vol 29 (2) ◽  
pp. 142-149 ◽  
Author(s):  
Lizbeth González-Herrera ◽  
Patricia Rodríguez-Morales ◽  
María del Refugio González-Losa ◽  
Gerardo Pérez-Mendoza ◽  
Jaqueline Canul-Canché ◽  
...  

We performed a case-control association study to evaluate the association between common polymorphisms in MTHFR (C677T and A1298C) and the Arg72Pro polymorphism in the p53 gene and the risk for cervical intraepithelial neoplasia (CIN) or invasive cervical cancer (ICC) in Mexican HPV-infected women. We included 131 women with diagnosis of CIN grade I-II and 78 with CIN III or ICC; as controls we also included 274 women with normal Pap smear and negative HPV test. Genotyping for MTHFR and p53 polymorphisms was performed by PCR-RFPLs. HPV was tested by Hybrid Capture II. Odds ratios and 95% confidence intervals were estimated. Genotype frequencies for the 3 studied polymorphisms were distributed according to the Hardy-Weinberg equilibrium. The A1298C-MTHFR polymorphism showed significant differences for the heterozygous AC genotype and the C allele, whereas the AA genotype and A allele resulted to be genetic risk factors for CIN or ICC (p<0.03). The Arg72Pro-p53 polymorphism showed for the genotypes Arg/Pro and Pro/Pro, and for the Pro allele, a significant association only to the risk for CIN (p<0.03). The MTHFR/p53 interaction showed that the genotype combinations AA/ArgArg and AA/ArgPro were associated, respectively, to the risk of ICC and CIN (p<0.05). This study suggests that the A1298C-MTHFR polymorphism contributes to the genetic risk for both CIN and ICC, whereas the Arg72Pro-p53 polymorphism only contributes to the risk for CIN. The MTHFR/p53 genetic combinations AA/ArgArg and AA/ArgPro are associated genetic risk factors for ICC and CIN in Mexican HPV-infected women.


2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaoyu Zhu ◽  
Ji Ren ◽  
Dianqin Xu ◽  
Di Cheng ◽  
Wei Wang ◽  
...  

Outside a few affluent countries with adequate vaccination and screening coverage, cervical cancer remains the leading cause of cancer-related deaths in women in many countries. Currently, a major problem is that a substantial proportion of patients are already at an advanced cancer stage when diagnosed. There is increasing evidence that indicates the involvement of translationally controlled tumor protein 1 (TPT1) overexpression in cancer development, but little is known about its implication in cervical cancer. We assessed the levels of TPT1 in surgical tissue and sera of patients with cervicitis, cervical intraepithelial neoplasia III, and cervical cancer, as well as in normal and cancerous cervical cell lines. Gene sets, pathways, and functional protein interactions associated with TPT1 were identified using the TCGA data cohort of cervical cancer. We found that the TPT1 expression was significantly increased in cervical cancer tissue compared to all nonmalignant cervical tissues, including samples of cervicitis, cervical intraepithelial neoplasia III, and normal controls. Serum level of TPT1 was also increased in cervical cancer patients compared to healthy subjects. Furthermore, elevated TPT1 expression was significantly correlated with lymph node metastasis and a low differentiation degree of the cancer. In the cancerous tissues and cell lines, selective markers of PI3K/AKT/mTOR pathway over-activation, apoptosis repression, and EMT were detected, and their interaction with TPT1 was supported by biometrics analyses. Our results, for the first time, demonstrate a strong correlation of upregulated TPT1 expression with cervical cancer progression, suggesting that TPT1 might provide a potential biomarker for cervical cancer progression.


2020 ◽  
Vol 70 (6) ◽  
pp. 503-509
Author(s):  
Amir Sohrabi ◽  
Fatemeh Bassam-Tolami ◽  
Mohsen Imani

Abstract Background HPV genotypes are the most common etiological factor for genital neoplasia. It would appear that sexually transmitted infections accompanied with HPV genotypes might have synergistic interactions in cancer progression. The genetic polymorphisms are involved in metabolizing carcinogens which may contribute to the susceptibility of developing genital cancers by less efficient or overly down metabolic pathways and cell signaling. MTHFR polymorphisms are related to several metabolic disorders and human cancers. We investigated the contribution of MTHFR 1298 and MTHFR 677 polymorphisms as potential risk factors for outcomes with HPV genotypes and STIs in Iranian population. Materials and Methods As a case–control study, MTHFR A1298C and C677T were assessed for SNPs analysis using a PCR–RFLP assay in 50 cervical intraepithelial neoplasia (CIN) cases, 98 HPV-positive subjects and 47 non-cancerous/non-HPV patients as healthy controls. Results Finding suggested a significant association between the MTHFR 1298 CC polymorphisms (OR = 3.5, 95% CI = 1.13–10.82, P ≤ 0.05) in women with CIN as compared to non-cancerous/non-HPV subjects. There was not a significant difference of MTHFR 677 between outcomes. Discussion It would seem MTHFR 1298 CC is more likely to be a potential risk factor for HPV–cervical cancer progression. Consequences support further attempts to understand the clinical manifestations of neoplasia related to genital infections and gene mutations.


Author(s):  
Travis T. Sims ◽  
Lauren E. Colbert ◽  
Ann H. Klopp

ABSTRACT The microbiome, which refers to the microbiota within a host and their collective genomes, has recently been demonstrated to play a critical role in cancer progression, metastasis, and therapeutic response. The microbiome is known to affect host immunity, but its influence on human papilloma virus (HPV) gynecologic malignancies remains limited and poorly understood. To date, studies have largely focused on the cervicovaginal microbiome; however, there is growing evidence that the gut microbiome may interact and substantially affect therapeutic response in gynecologic cancers. Importantly, new developments in microbiome sequencing and advanced bioinformatics technologies have enabled rapid advances in our understanding of the gut and local tumor microbiota. In this review, we examine the evidence supporting the role of the microbiome in HPV-associated cervical intraepithelial neoplasia (CIN) and cervical cancer, explore characteristics that influence and shape the host microbiota that impact HPV-driven carcinogenesis, and highlight potential approaches and considerations for future and ongoing research of the microbiome's effect on HPV-associated cancer.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Rhafaela L. Causin ◽  
Luciane S. da Silva ◽  
Adriane F. Evangelista ◽  
Letícia F. Leal ◽  
Karen C. B. Souza ◽  
...  

New prevention strategies are needed to detect cervical intraepithelial neoplasia (CIN). The microRNA expression analysis has already been reported as molecular biomarkers in the early detection of cervical cancer (CC) through minimally invasive samples, such as liquid biopsy, obtained through collection using liquid-based cytology (LBC). In this study, we aimed to identify molecular signatures of microRNAs in cervical precursor lesions from LBC cervical and the molecular pathways potentially associated with the CC progression. We analyzed 31 LBC cervical samples from women who underwent colposcopy. These samples were divided into two groups: the first group was composed of samples without precursor lesions of CC, considering the control group, referred to as healthy female subjects (HFS; n = 11 ). The second group corresponded to women diagnosed with cervical interepithelial neoplasia grade 3 (CIN 3; n = 20 ). We performed microRNA and gene expression profiling using the nCounter® miRNA Expression Assays (NanoString Technology) and PanCancer Pathways (NanoString Technology), respectively. A microRNA target prediction was performed by mirDIP, and molecular pathway interaction was constructed using Cytoscape. Bidirectional in silico analyses and Pearson’s correlation were performed for associated the relation between genes, and miRNAs differentially expressed related cervical cancer progression were performed. We found that the expression of nine microRNAs was significantly higher, two were downregulated (miR-381-3p and miR-4531), and seven miRNAs were upregulated (miR-205-5p, miR-130a-3p, miR-3136-3p, miR-128-2-5p, let-7f-5p, miR-202-3p, and miR-323a-5p) in CIN 3 ( fold   change ≥ 2 and p ≤ 0.05 ). The miRNA expression patterns were independent of hr-HPV infection. We identified four miRNAs (miR-205-5p, miR-130a-3p, miR-4531, and miR-381-3p) that could be used as biomarkers for CIN 3 in LBC samples through multiple logistic regression analyses. We found 16 genes differentially expressed between CIN 3 and HSF samples ( fold   change ≥ 2 and p ≤ 0.05 ). We found the correlation between miR-130a-3p and CCND1( R = − 0.52 ; p = 0.0029 ), miR-205-5p and EGFR ( R = 0.53 ; p = 0.0021 ), and miR-4531 and SMAD2 ( R = − 0.54 ; p = 0.0016 ). In addition, we demonstrated the most significant pathways of the targets associated with cervical cancer progression (FDR-corrected p < 0.001 ). This study demonstrated that miRNA biomarkers may distinguish healthy cervix and CIN 3 and regulate important molecular pathways of carcinogenesis.


2016 ◽  
Vol 10 (2) ◽  
pp. 45-49
Author(s):  
P Shrestha ◽  
P Koirala ◽  
M Singh

Aims: The objective of this study was to assess the risk factors of preinvasive and invasive cervical cancer.Methods: This was a prospective hospital based case control study conducted from April 2012 to April 2013, which included 91 patients in each group. Among cases, 34 were Cervical Cancer and 57 were Cervical Intraepithelial Neoplasia. Simple random method was adopted for selecting patients. Prefixed questionnaire was used. Statistical analysis was done using SPSS 19.0.Results: In multivariate analysis, history of abnormal vaginal discharge and cigarette smoking were significantly associated with cervical cancer (p value of 0.001 and 0.003 respectively) and Cervical Intraepithelial Neoplasia (p <0.001). Whereas, early age at first sexual intercourse ≤ 16 years and more than one sexual partner of husband had only borderline significance for Cervical cancer (p value 0.049 and 0.038 respectively).Conclusions: Cigarette smoking and abnormal vaginal discharge were significantly associated with cervical cancer. 


Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3291
Author(s):  
Akihito Yamamoto ◽  
Seiryu Kamoi ◽  
Keisuke Kurose ◽  
Marie Ito ◽  
Toshiyuki Takeshita ◽  
...  

(1) Background: Previous reports have indicated that cancers of the stomach, lung, and pancreas can be detected by dog sniffing, but results have been varied. Here, a highly trained dog was used to determine whether urine from patients with cervical premalignant lesions and malignant tumors have a cancer-specific scent. (2) Methods: A total of 195 urine samples were collected from patients with cervical cancer, cervical intraepithelial neoplasia grade 3 (CIN3), benign uterine diseases, and healthy volunteers. Each test was performed using one urine sample from a cancer patient and four samples from different controls. Each of the five urine samples was placed in a separate box. When the cancer sniffing dog stopped and sat in front of the box with a sample from a cancer patient, the test was considered as positive. (3) Results: 83 patients with cervical cancer (34 cases of cervical cancer and 49 cases of cervical intraepithelial neoplasia grade 3), 49 patients with uterine benign diseases, and 63 healthy volunteers were enrolled, and their urine samples were collected. In 83 times out of 83 runs in a double-blind test, the trained dog could correctly identify urine samples of cervical cancer patients. (4) Conclusion: A trained dog could accurately distinguish the urine of all patients with cervical cancer or CIN3, regardless of the degree of cancer progression.


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