Cellular senescence molecules expression in type 2 diabetes mellitus: CDKN2A, CDKN2B, and lncRNA ANRIL.

AIMS: Cellular senescence in type 2 diabetes mellitus (T2DM) has received widespread attention. However, the cellular senescence molecules involved in T2DM are unclear. Furthermore, there are no consistent biomarkers for cellular senescence in T2DM. Therefore, this study aimed to identify cellular senescence molecules in T2DM and investigate their expression in peripheral blood mononuclear cells of individuals with T2DM. METHODS: Patients with T2DM (n = 40) and healthy controls (n = 40) were enrolled. We used different databases to identify cellular senescence molecules in T2DM and confirmed the obtained genes and lncRNA using real-time PCR. RESULTS: Bioinformatics analysis indicated that CDKN2A and CDKN2B genes, and long noncoding RNA ANRIL are the most effective cellular senescence molecules in T2DM. Furthermore, CDKN2A and ANRIL expression decreased in individuals with T2DM. CONCLUSIONS: Cellular senescence may have a protective effect against T2DM. In addition, the cellular senescence molecules CDKN2A and ANRIL may be potential biomarkers of cellular senescence in T2DM.

Molecular Mechanisms of miR-214 Involved in Cancer and Drug Resistance.

As a transcriptional regulation element, the microRNA plays a crucial role in many aspects of molecular biological processes, like cellular metabolism, cell division, cell death, cell movement, intracellular signaling, and immunity. Previous studies suggested that microRNA-214 (miR-214) is probably a valuable cancer marker. In this study, a brief updated overview of the vital dual role of miR-214 in cancer as a tumor suppressor or oncogene was provided. We also examined target genes and signaling pathways related to the dysregulation of miR-214 reported in previous experimental research on various human diseases. To highlight the critical function of miR-214 in the prognostic, diagnostic, and pathogenesis of cancer diseases, we focused on the probable clinical biomarker and drug resistance function of miR-214. The current research provides a comprehensive perspective of the regulatory mechanisms governed by miR-214 in human disease pathogenesis and a list of probable candidates for future study.

Construction of circRNA-miRNA-mRNA network in the pathogenesis of recurrent implantation failure using integrated bioinformatics study.

This research attempted to elucidate the molecular components are involved in the pathogenesis of recurrent implantation failure (RIF). We initially identified that 386 mRNAs, 144 miRNAs and 2548 circRNAs were differentially expressed (DE) in RIF and then investigated the genetic cause of the observed abnormal expression by constructing a circRNA-miRNA-mRNA network considering the competing endogenous RNA theory. We further analysed the upstream transcription factors and related kinases of DEmRNAs (DEMs) and demonstrated that SUZ12, AR, TP63, NANOG, and TCF3 were the top five TFs binding to these DEMs. Besides, protein-protein interaction analysis disclosed that ACTB, CXCL10, PTGS2, CXCL12, GNG4, AGT, CXCL11, SST, PENK, and FOXM1 were the top 10 hub genes in the acquired network. Finally, we performed the functional enrichment analysis and found that arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), pathways in cancer, TNF signalling pathway and steroid hormone biosynthesis were the potentially disrupted pathways in RIF patients. Optimistically, our findings may deepen our apprehensions about the underlying molecular and biological causes of RIF and provide vital clues for future laboratory and clinical experiments that will ultimately bring a better outcome for patients with RIF.

The expanding role of CDR1-AS in the regulation and development of cancer and human diseases.

CircRNAs are a superabundant and highly conserved group of noncoding RNAs (ncRNAs) that are characterized by their high stability and integrity compared with linear forms of ncRNAs. Recently, their critical role in gene expression regulation has been shown; thus, it is not far-fetched to believe that their abnormal expression can be a cause of different kinds of diseases such as cancer, neurodegenerative, and autoimmune diseases. They can have a function in variety of biological processes such as microRNA (miRNA) sponging, interacting with RNA-binding proteins, or even an ability to translate to proteins. A huge challenge in finding diagnostic biomarkers is finding noninvasive biomarkers that can be detected in human fluids, especially blood samples. CircRNAs are becoming candidate biomarkers for diagnosis and prognosis of these diseases through their ability to transverse from the blood-brain barrier and their broad presence in circulating exosomes. The circRNA for miRNA-7 (ciRS-7) is newly recognized, and acknowledged to being related to human pathology and cancer progression. In this review, we first briefly summarize the latest studies about their characteristics, biogenesis, and their mechanisms of action in the regulation and development of human diseases. Finally, we provide a list of diseases that are linked to one member of this novel class of ncRNAs called ciRS-7.

The effects of water-pipe smoking on birth weight: a population-based prospective cohort study in southern Iran.

OBJECTIVES: Consecutive community health assessments revealed that water-pipe smoking in women and impaired growth in children were among the main health concerns in suburban communities in southern Iran. The aim of the present study was to identify the effects of water-pipe smoking during pregnancy on birth weight. METHODS: Data from a population-based prospective cohort study of 714 singleton live pregnancies in the suburbs of Bandar Abbas in southern Iran in 2016-2018 were used in this study. Data about water-pipe smoking patterns and birth weight were collected by questionnaires during and after the pregnancy. Low birth weight (LBW) was defined as a birth weight below 2,500 g. Statistical analyses were performed using generalized linear models, and the results were presented in terms of relative risk (RR) and 95% confidence intervals (CI). RESULTS: Fifty (8.2%) of the study subjects smoked water-pipe. The adjusted risk of LBW increased 2-fold in water-pipe smokers (adjusted RR [aRR], 2.09; 95% CI, 1.18 to 3.71), and by 2.0% for each 1-year increase in the duration of water-pipe smoking (aRR, 1.02; 95% CI, 0.99 to 1.05). CONCLUSIONS: Our results showed that water-pipe smoking during pregnancy was an important risk factor for LBW in this population sample from southern Iran. The introduction of regulations onto prevent water-pipe smoking and the implementation of community health action plans aiming at empowering women and increasing women's knowledge and awareness regarding the health consequences of water-pipe smoking are proposed.

An association study between CHEK2 gene mutations and susceptibility to breast cancer.

CHEK2 gene is known as a tumor suppressor gene in breast cancer (BC), which plays a role in DNA repair. The germ line mutations in CEHK2 have been associated with different types of cancer. The present study was aimed at studying the association between CHEK2 mutations and BC. Peripheral blood was collected from patients into a test tube containing EDTA, and DNA was extracted from blood samples. Then, we analyzed mutations including 1100delc, IVS2+1>A, del5395bp, and I157T within CHEK2 gene in patients with BC and 100 normal healthy controls according to PCR-RFLP, allelic specific PCR, and multiplex-PCR. Although IVS2+1G>A mutation within CHEK2 gene was found in two BC patients, other defined mutants were not detected. For the first time, we identified CHEK2 IVS2+1G>A mutation, one out of four different CHEK2 alterations in two Iranian BC patients (2%). Also, our results showed that CHEK2 1100elC, del5395bp, and I157T mutations are not associated with genetic susceptibility for BC among Iranian population.

Impaired expression of Drosha in breast cancer.

BACKGROUND: Impaired miRNAs processing pathway is one interesting scenario for global downregulation of the miRNAome in various types of malignancy. We previously reported that DGCR8 and Dicer genes dysregulated in patients with breast cancer. OBJECTIVE: To evaluate the expression pattern of Drosha in patients with breast cancer. METHODS: We evaluated the mRNA expression level of Drosha in 70 fresh breast carcinomas and adjacent non-neoplastic tissue using quantitative real-time PCR and assessed the possible correlation between its expression and clinicopathological parameters. RESULTS: Our results revealed that mRNA expression level of Drosha was decreased in tumors when compared to adjacent non-neoplastic tissue. However, this difference is not statistically significant (P > 0.05). Downregulation of Drosha is related to older age at diagnosis, higher histological grade, higher tumor size and metastasis. However, there was no significant correlation between Drosha expression level and clinicopathological parameters (P > 0.05). We found that Drosha expression negatively correlated with DGCR8 (P = 0.043), whereas dysregulated expression levels of Drosha and Dicer are positively correlated with to each other (P < 0.0001). CONCLUSION: This study provides evidence that the expression of Drosha is impaired in breast cancer. However, the molecular basis of observed expression pattern have remained inexplicable and should be further investigated.

Upregulation of the double-stranded RNA binding protein DGCR8 in invasive ductal breast carcinoma.

High-throughput experimental studies have indicated that the miRNAome is globally downregulated in various types of malignancy, and dysregulation of miRNAs processing component(s) is one possible mechanism for this phenomenon. Despite the progression in identifying cellular functions of Digeorge Syndrome Critical Region 8 (DGCR8) in miRNAs biogenesis, the role of altered expression of DGCR8 in the pathogenesis of invasive ductal breast carcinoma (IDC) has not yet been fully investigated. The objective of the present study was to evaluate DGCR8 mRNA expression in seventy fresh invasive ductal breast carcinomas and matched adjacent non-neoplastic tissues using quantitative real-time PCR and to assess the value of clinicopathological parameters on its expression. Our findings revealed that DGCR8 mRNA expression is upregulated in more than two-thirds of the cancerous specimens (68.66%) when compared to adjacent non-neoplastic tissue. This difference is statistically significant (P<0.05). We found that DGCR8 mRNA levels were increased in the high-grade and metastatic compared with those of both low-grade and non-metastatic. We demonstrated that there is not significant correlation between DGCR8 mRNA expression levels and clinicopathological parameters. In conclusion, our study suggested that upregulation of DGCR8 may be involved in tumorigenesis and aggressiveness of IDC and may serve as future therapeutic target.

Dysregulated expression of Dicer in invasive ductal breast carcinoma.

Several lines of evidence suggest that the global down-regulation of the microRNAome (miRNAome) involved in pathogenesis of various malignancies. Impaired microRNAs processing pathway is one possible mechanism for global down-regulation of the miRNAome. Dicer is a key enzyme in miRNA processing pathway, and dysregulation of its expression has been suggested as a possible cause of miRNAome alterations observed in various cancers. However, Dicer mRNA expression in invasive ductal breast carcinoma (IDC) has not been investigated in depth. Therefore, this study aimed to evaluate the mRNA expression of Dicer in IDC and also to assess the correlation of its expression with clinicopathological parameters including age, histological grade, tumor size and lymph node metastasis. We investigated the expression of the Dicer in seventy fresh invasive ductal breast carcinomas and matched adjacent non-neoplastic tissue by quantitative real-time PCR using validated reference genes. In addition, the possible impact of clinicopathological characteristics on Dicer expression levels was analyzed. Our results showed that Dicer mRNA expression is down-regulated in slightly more than half (51.43 %) of the tumor specimens when compared to adjacent non-neoplastic tissue. Comparison of the Dicer expression level between tumor and matched adjacent non-neoplastic tissue showed that there is no statistical significant differences between them (P = 0.425). We also found that Dicer mRNA expression in IDC samples was not correlated with clinicopathological features. In conclusion, our findings provide additional evidence to support the hypothesis that Dicer expression down-regulated in breast cancer. This study suggested that the decreased expression of Dicer may be potential underlying mechanism in pathogenesis of IDC.

The impact of human papillomavirus (HPV) types 6, 11 in women with genital warts.

OBJECTIVE: Human papillomaviruses (HPV) are etiologically associated with the development of virtually all genital warts. HPV-6 and HPV-11 are the most commonly detected HPV genotypes, but at least 20 other HPV genotypes have occasionally been found in genital wart tissue specimens. STUDY DESIGN: The aim of this study was to determine from 100 genital wart tissue specimens collected from female patients using multiplex gap-PCR technique the prevalence of various genital HPV among women with HPV genital warts in south of Iran. 100 genital wart tissue specimens were tested for the presence of HPV PG5/PG6 and also for HPV type using polymerase chain reaction (PCR). RESULTS: Based on the collected data, 73 (73 %) samples were detected positive for HPV DNA and 23 (23 %) samples out of 100 samples were detected negative for HPV DNA. 49 (49 %) and 67 (67 %) of patients were detected positive for HPV type 6 and 11, respectively. There was a significant association between marital status and HPV genotype 6 (OR = 0.51, 95 % CI = 0.37-0.70, P = 0.01). Nevertheless, no significant association was found between marriage and HPV genotype 11 (OR = 0.85, 95 % CI = 0.58-1, 24, P = 0.7). Similarly, this result was demonstrated, in combined marriage and HPV-general (OR = 0.80, 95 % CI = 0.62-0.05, P = 0.4). CONCLUSION: Concerning the prevalence of HPV in our study, determination of genital HPV prevalence and multiple infections among the normal population of women of Hormozgan Province is recommended.

Effect of anti-inflammatory (IL-4, IL-10) cytokine genes in relation to risk of cervical carcinoma.

OBJECTIVES: Cervical cancer is rated the second most common malignant tumor globally and is etiologically linked to human papillomavirus infection. Interleukin-4 (IL-4) and IL-10 are cytokines with anti-inflammatory properties. The purpose of this study was to determine the relationship of different alleles of IL-4 and IL-10 genes with risk of cervical cancer among passive smokers and users of oral contraceptives. MATERIALS AND METHODS: We investigated the association of cervical cancer with 2 anti-inflammatory cytokine genes IL-4 and IL-10 using a case-control study. The study sample comprised 200 cases of cervical cancer and an equal number of matched controls who were investisgated by variable number of tandem repeat and Restriction Fragment Length Polymorphism analysis. RESULTS: In this study we observed that the Rp1/Rp2 genotype of IL-4 marginally increased the risk of developing cervical cancer [odds ratio (OR), 1.3; 95% confidence intervals (CI), 0.45-3.64; P=0.8]. In case of passive smokers we also found a marginal increase in the risk for cervical cancer with AC and combined AC+CC genotypes (OR, 1.7; 95% CI, 0.90-3.34; P=0.1; and OR,1.7; 95% CI, 0.90-3.17; P=0.1, respectively). However, a nonsignificant association was observed between use of oral contraceptives and risk of cervical cancer with anti-inflammatory cytokine genotypes. CONCLUSIONS: This study suggests that passive smokers among North Indian women having IL-4 Rp1/Rp2 and IL-10 (AC) genotypes had an increased risk for developing cervical cancer.

Hypermethylation-mediated partial transcriptional silencing of DAP-kinase gene in bladder cancer.

Death-associated protein kinase (DAP-kinase) is a novel serine/threonine kinase whose expression is required for interferon-gamma-induced apoptosis. This study evaluated the methylation pattern and its impact on the expression of the DAP-kinase gene in transitional cell carcinoma of the bladder as hypermethylation is one of the earliest and most frequent alterations leading to cancer. The frequency of hypermethylation of the gene promoter was 37.8%. On correlation with clinicopathological features, methylation was seen mostly in superficial tumours in the group aged > 60 years (42.9 vs 33.3% of those 60 years and with a smoking habit showed increased downregulation of mRNA compared with non-smokers of this age group (similar pattern of methylation). Hypermethylation can decrease the expression of DAP-kinase and may be one of the reasons for conversion of normal cells to malignant cells, as the frequency of methylation at the early stage (superficial) of tumours was elevated. Methylation of DAP-kinase can be considered as one of the prognosis indicators for progression and development of bladder cancer.

Interleukin-12 gene polymorphism and cervical cancer risk.

AIM: : To investigate the effect of interleukin-12 p40 gene (IL-12ß) 3'-untranslated region polymorphism on the risk of cervical cancer. METHODS: DNA was isolated from peripheral blood of 200 patients with cervical cancer and 200 healthy controls. Polymerase chain reaction restriction fragment length polymorphism was used for the detection of IL-12ß (1188A/C) gene polymorphism. RESULTS: It was observed that genotypes AC [odds ratio (OR) = 1.80, 95% confidence interval (CI) = 1.17-2.78] and AC + CC (OR = 1.71, 95% CI = 1.11-2.63, P = 0.01) increase the risk of cervical cancer. The strength of the risk in passive smokers with AC and AC + CC genotypes was increased to more than 2.8 times in comparison with a nonsmoker with AA genotype (OR = 2.94, 95% CI = 1.56-5.55, P < 0.001; OR = 2.83, 95% CI = 1.52-5.31, P < 0.001, respectively). CONCLUSION: This is the first study to provide an evidence for the association of IL-12ß (1188A/C) gene polymorphism with the risk of cervical cancer.

No association of TAP1 and TAP2 genes polymorphism with risk of cervical cancer in north Indian population.

BACKGROUND: Transporter associated with antigen processing (TAP), a member of the ATP-binding cassette transporter super family, is composed of two integral membrane proteins, TAP-1 and TAP-2. The TAP gene product is involved in the processing of endogenous peptides that bind to MHC class I molecules. Mutations and/or polymorphism within these genes could alter the efficacy of the immune response which might be relevant for the development of autoimmune diseases and cancer. METHODS: DNA was isolated from peripheral blood sample of 200 patients with cervical cancer and 200 healthy controls. TAP1 and TAP2 allele polymorphism were determined by polymerase chain reaction. RESULT: Significant protective OR (OR = 0.22 95% CI = 0.09-0.51, P < 0.001-OR = 0.47, 95% CI = 0.24-0.92, P = 0.02) was observed for GG and combined AG+GG genotypes of TAP2 in patients with SCC respectively. Similarly, such genotypes (GG, AG+GG) appeared same OR for patient with cervical cancer in study group (OR = 0.12, 95% CI = 0.04-0.39-P < 0.001-OR = 0.5 ,95% CI = 0.25-0.95-P = 0.03). There was decrease risk of cervical cancer in user of oral contraceptive with AG and GG genotypes of TAP2 (OR = 0.55, 95% Cl = 0.41-0.73, P = 0.002, OR = 0.09, 95% CI = 0.02-0.36, P < 0.001) respectively. In case of TAP1 gene all allelic polymorphisms showed a decrease OR in patients with cervical cancer in passive smokers and user of oral contraceptives, though, no significant CONCLUSION: Thus, TAP1 and TAP2 genes polymorphism are not linked to cervical carcinoma, since no association was found between a particular genotype and the disease.

Methylation patterns of Rb1 and Casp-8 promoters and their impact on their expression in bladder cancer.

Aberrant methylation of the promoter CpG island of human genes is an alternative gene inactivation mechanisms that contributes to the carcinogenesis of human tumors. We tried to determine the methylation status and its impact on the expression of two tumor related genes Casp-8 and Rb1 in 103 bladder tumor tissues and 48 control paraffin-embedded tissues by using MSP-PCR and SQRT-PCR. Of the patients, 19.4% for Casp-8 and 28.2% for Rb1 showed methylation in bladder cancer. There were significant differences between patients and healthy controls in methylation of Rb1 (p = 0.001) and Casp-8 (p = 0.008) and especially when both genes methylated (p = 0.004). Methylation of Casp-8 has mostly been taken places in patients with age >60 years (p = 0.013) whereas methylation of Rb1 has taken place in age >60 (p = 0.018) as well as in patients age <60 (p = 0.027). Patients with methylated of both genes with stage T2 showed an increasing risk of 4.75 fold (95% CI = 2.87-7.85, p = 0.00) and for stage T3, 23.50 fold (95% CI = 6.05-91.21, p = 0.00) of bladder cancer. Smoking showed a high significant effect on methylation (p = 0.00 in compare to non-smoker patients), especially in those with pack-years more than 44.7 (OR = 3.53, 95% CI = 1.69-7.35, p = 0.001). The risk of bladder cancer was marginally associated in drinker patients (OR = 1.78, 95% CI = 1.42-2.24, p = 0.010) featuring both genes methylated, especially in those patients consumed alcohol units>30 per week (OR = 4.57, 95% CI = 2.38-8.80, p = 0.000). Significant reduction in expression has been detected in patients with methylated Rb1 (p = 0.00) and Casp-8 (p = 0.03). These results suggest that age, smoking and drinking will increase the probability of methylation of these genes and consequently increased risk of developing of bladder cancer to higher stages of disease. Interestingly, it has been deduced that methylation by itself maybe significantly have a role on reducing the expression ofRb1, but it seems that methylation along with risk factors lead to decrease the expression of Casp-8. Methylation of Rb1 can be considered as one of prognosis indicator for progression and development bladder cancer.

Association of interleukin-18 gene promoter polymorphism on the risk of cervix carcinogenesis in north Indian population.

Cervical cancer is one of the most common neoplastic diseases affecting women, with a combined worldwide incidence of almost half a million new cases. Considering the fact that IL-18 plays an important role in the interactions among T cells, NK cells, and macrophages and induces IFN-gamma production, efforts should be made to understand the clinical impact of IL-18 cytokine in patients with solid malignancies, as not much study has been conducted in cervix carcinoma. In this study, we have observed in GC genotype statistically significant marginal increased risk of developing of cervical cancer (OR 1.8, 95% CI 1.17-2.76, p = 0.006). Similarly, when the GC with CC genotypes were combined results were once more statistically significant with borderline risk of developing cervix cancer (OR 1.6,95% CI 1.09-2.50, p = 0.01). Likewise, we found statistically significant increased risk between cases and controls in GC genotype and passive smokers with risk of cervical cancer (OR 4.3, 95%CI 2.13-8.99, p = 0.00001). Our investigation suggests that IL-18 gene -137 in different genotypes, as also in passive smokers, may increase risk of cervix carcinogenesis in north Indian women.

Association of genetic polymorphism of the DNA base excision repair gene (APE-1 Asp/148 Glu) and HPV type (16/18) with the risk of cervix cancer in north Indian population.

Cervical cancer is one of the most common neoplastic diseases affecting women, with a combined world wide incidence of almost half a million new cases. Reduced DNA repair capacity (DRC) can render a high risk of developing many types of cancer; including cervical cancer. Polymorphisms in DNA repair genes may contribute the genetic instability and carcinogenesis. Smoking experience and use of oral contraceptives have been confirmed to be risk factors for cervical cancer. The purpose of the present study was, therefore to investigate APE-1 genotypes (Asp/Asp, Asp/Glu, Glu/Glu) with different histological subtypes in cases compared with controls. It has been observed that Asp/Glu with Glu/Glu genotypes that combined we observed statistically significant with protective effect for developing of cervix cancer (OR-0.51, 95% CI 0.31-0.83, p-0.006). The combined Asp/Glu with Glu/Glu genotypes who were using oral contraceptives were shown to be statistically significant with reduced risk of cervical cancer (OR-0.22 95% CI- 0.11-0.47, p-0.0002). It has been suggested that significantly correlation between HPV 16 and users of oral contraceptives in certain APE-1 genotypes with reduced risk in developing cervix cancer. In conclusion we observed statistical significant association with reduced risk of cervix cancer in APE-1 with different genotypes, though, on the other hand, in association between HPV type 18 and those having SCC, highly increased risk of cervical cancer was observed.

Impact of methylenetetrahydrofolate reductase (MTHFR) codon (677) and methionine synthase (MS) codon (2756) on risk of cervical carcinogenesis in North Indian population.

Cervical cancer continues to be the most common cause of death among women in developing countries. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are critical enzymes of folate metabolic pathways. In this work, we have conducted a case-control study to assess the role of these two polymorphisms in cervical cancer development. We obtained blood samples from 200 women with cervical cancer and from equal matched controls and analysed using PCR-RFLP method. We found that the methylenetetrahydrofolate reductase variant CT and CT+TT genotypes decreased cervix cancer risk, statistically significant (OR:0.30, 95% CI: 0.18-0.51, P<0.001 for CT and OR:0.29, 95% CI: 0.18-0.49, P=0.0000006 for CT+TT). Similarly in those patients who used oral contraceptive with variant CT genotype, there was statistically highly significant reduced risk of cervix cancer (OR:0.25, 95% CI: -0.12-0.49, P<0.001) of methylenetetrahydrofolate reductase gene. For the methionine synthase, 2756 variant AG and AG+GG genotypes were similarly associated with highly significant reduced risk of cervix cancer (OR: 0.13, 95% CI: 0.07-0.26, P<0.001 for AG, and OR: 0.15, 95% CI: 0.08-0.27, P<0.001 for AG+GG) genotypes. In conclusion, our study suggested that methylenetetrahydrofolate reductase and methionine synthase polymorphisms might have protective effect on the risk of cervical cancer in the North Indian women.

Impact of polymorphism in IL-1RA gene on the risk of cervical cancer.

INTRODUCTION: Cervical cancer, the second most common malignancy in women worldwide, is almost invariably associated with infection by human papillomavirus (HPV). However, although many women are infected with high-risk types of HPV, only a subset of infected women will ever develop cervical cancer. Therefore, host genetic factor may play a role in cervical carcinogenesis. Several studies suggested that immunological components play a key role in the development of cervical cancer. Polymorphism in the IL-1RA gene was associated with various malignant diseases. Data are lacking for cervical cancer. MATERIALS AND METHODS: In a case-control study we analyzed the polymorphism of IL-1RA in 150 women with cervical cancer and 209 healthy controls. Genomic DNA fragments were amplified by PCR. RESULTS: There was a strong significantly protective association between heterozygous AB genotype and HPV 18 (OR = 0.11, 95% CI = 0.04-0.30, p = 0.0000000). Similarly this result was demonstrated, in combined AB + BB genotypes of IL-1RA with HPV 18 (OR = 0.12, 95% CI= 0.05-0.30, p = 0.0000000) and HPV type 16 + 18 (OR = 0.18,95% CI = 0.08-0.38, p = 0.000005). We found high protective significant association between heterozygous genotype AB with adenocarcinoma (OR = 0.19, 95% CI = 0.09-0.40, p = 0.0000002) as well. CONCLUSION: These findings therefore suggest that the IL1-RA polymorphism is associated with cervical cancer.

Interleukin 1 beta gene polymorphism and risk of cervical cancer.

OBJECTIVE: To determine whether a polymorphism at position +3953 in exon 5 of the lL-1beta gene (IL-1beta +3953), a condition associated with an increased risk for a number of inflammatory diseases, is also involved in the development of cervical cancer. METHOD: We isolated DNA from peripheral blood in 150 women with cervical cancer and 200 healthy controls, and IL-1beta +3953 allele polymorphism was determined by polymerase chain reaction. RESULTS: Genotypes A1/A2 and A2/A2+A1/A2 were associated with increased risk of cervical cancer (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.78-4.67; P<0.001 and OR, 2.85; 95% CI, 1.77-4.6; P<0.001, respectively). The risk in a passive smoker with A2/A2 or A1/A2 genotype was increased more than 5-fold (OR, 5.69; 95% CI, 2.61-12.50; P<0.001) compared with a nonsmoker with the A1/A1 genotype. CONCLUSION: This study provides evidence of an association between lL-1beta +3953 polymorphism and risk of cervical cancer.