Impacts of Chemokine (C-X-C Motif) Receptor 2 C1208T Polymorphism on Cancer Susceptibility

Background. The CXC chemokines belong to a unique family of cytokines that participates in the progression and development of many malignant tumors. Evidence for the relationship between chemokine (C-X-C motif) receptor 2 (CXCR2) C1208T polymorphism and susceptibility to cancer remains inconsistent. Methods. Odds ratios (ORs), 95% confidence intervals (CIs), and combined analysis were used to investigate the effect of CXCR2 variation on cancer risk. Gene Set Enrichment Analysis (GSEA) and enzyme-linked immunosorbent assay (ELISA) were also used to evaluate the expression of CXCR2 in prostate cancer (PCA). Results. Across 11 case-control studies, 4,909 cases and 5,884 controls were involved in the current analysis. Individuals with a TT genotype were associated with increased risk of digestive cancer, compared to those with a TC+CC genotype ( OR = 1.16 , 95 % CI = 1.02 -1.31, P = 0.025 ). Individuals carrying the TT genotype had a 39% higher risk of urinary cancer than those carrying CC genotype ( OR = 1.39 , 95 % CI = 1.04 -1.87, P = 0.025 ). Individuals with a TT genotype showed a 56% augmented breast cancer risk, compared to those with a CC genotype ( OR = 1.56 , 95 % CI = 1.03 -2.35, P = 0.034 ). It was found that CXCR2 expression was downregulated in PCA. Compared with PCA subjects carrying the CC genotype, the expression of CXCR2 was decreased in patients with the TT genotype. Conclusions. The CXCR2 C1208T variation was associated with elevated risk of urinary, breast, and digestive cancer. However, the C1208T polymorphism was correlated with attenuated risk of lung cancer.

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Association Between LncRNA MALAT1 Polymorphisms and Cancer Risk: A Meta-Analysis Based on7007 Cases and 8791 Controls

10.21203/rs.3.rs-42022/v1 ◽

2020 ◽

Author(s):

Lei Zheng ◽

Lijuan Rong ◽

Zhenyun Cheng

Keyword(s):

Cancer Risk ◽

Confidence Interval ◽

Cancer Susceptibility ◽

Meta Analysis ◽

Dominant Model ◽

Digestive Cancer ◽

Increased Risk ◽

Lncrna Malat1 ◽

Risk Of Cancer ◽

Allelic Model

Abstract Background: LncRNA metastasis associated with lung adenocarcinoma transcript-1 (MALAT1) was involved in pathogenesis and progress of diverse cancers. To investigate the association of MALAT1 and cancer susceptibility, this meta-analysis was appraised.Methods: 12 studies including 7007 cancer patients and 8791 controls were selected for this meta-analysis. Ratio radiation (ORS) and 95% confidence interval (CIS) were used to assess cancer susceptibility.Results: There was no significant association between rs3200401 polymorphism and the risk of cancer. However, rs3200401 was correlated with an increased risk of digestive cancer in allelic model (OR=1.15, 95%CI=1.04-1.28, P=0.009) and dominant model (OR=1.16, 95%CI=1.02-1.31, P=0.02). There was a borderline association between rs664589 and cancer susceptibility under the dominant model (OR=1.17, 95%CI=1.00-1.38, P=0.05). Rs619586 was associated with decreased cancer risk in all populations under four models (G vs A: OR=0.86, 95%CI=0.78-0.94, P=0.001; GG vs AA: OR=0.60, 95%CI=0.42-0.84, P=0.003; GG+AG vs AA: OR=0.87, 95%CI=0.78-0.97, P=0.009; GG vs AG+AA: OR=0.61, 95%CI=0.44-0.84, P=0.003). Moreover, rs1194338 was decreased associated with cancer susceptibility (A vs C: OR=0.89, 95%CI=0.80-0.98, P=0.01; AA vs CC: OR=0.77, 95%CI=0.62-0.96, P=0.02; AA+AC vs CC: OR=0.87, 95%CI=0.77-1.00, P=0.04; AA vs AC+CC: OR=0.82, 95%CI=0.67-1.00, P=0.05).Conclusion: Our results suggest that rs619586 and rs1194338 are associated with decreased cancer risk, while rs3200401 and rs664589 correlated with increased digestive cancer risk.

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ERCC1 rs11615 polymorphism increases susceptibility to breast cancer: a meta-analysis of 4547 individuals

Bioscience Reports ◽

10.1042/bsr20180440 ◽

2018 ◽

Vol 38 (3) ◽

Cited By ~ 3

Author(s):

Bingjie Li ◽

Xiaoqing Shi ◽

Yingying Yuan ◽

Mengle Peng ◽

Huifang Jin ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cancer Susceptibility ◽

Excision Repair ◽

Meta Analysis ◽

Asian Population ◽

Dominant Model ◽

Case Control Studies ◽

Increased Risk

Excision repair cross-complementation group 1 (ERCC1), a DNA repair protein, is vital for maintaining genomic fidelity and integrity. Despite the fact that a mounting body of case–control studies has concentrated on investigating the association of the ERCC1 rs11615 polymorphism and breast cancer risk, there is still no consensus on it. We conducted the current meta-analysis of all eligible articles to reach a much more explicit conclusion on this ambiguous association. A total of seven studies involving 2354 breast cancer cases and 2193 controls were elaborately selected for this analysis from the Embase, EBSCO, PubMed, WanFang, and China National Knowledge Infrastructure (CNKI) databases. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated in our meta-analysis. We found that the ERCC1 rs11615 polymorphism was significantly associated with breast cancer risk under all genetic models. When excluded, the studies that deviated from Hardy–Weinberg equilibrium (HWE), the pooled results of what remained significantly increase the risk of breast cancer under the allele model (OR = 1.14, 95% CI = 1.02–1.27, P=0.02), heterozygote model (OR = 1.24, 95% CI = 1.06–1.44, P=0.007), and dominant model (OR = 1.21, 95% CI = 1.05–1.41, P=0.01). This increased breast cancer risk was found in Asian population as well as under the heterozygote model (OR = 1.24, 95% CI = 1.05–1.48, P=0.013) and dominant model (OR = 1.20, 95% CI = 1.02–1.42, P=0.03). Our results suggest that the ERCC1 rs11615 polymorphism is associated with breast cancer susceptibility, and in particular, this increased risk of breast cancer existence in Asian population.

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Association of Five Snps in Cytotoxic T-Lymphocyte Antigen 4 and Cancer Susceptibility: Evidence from 67 Studies

Cellular Physiology and Biochemistry ◽

10.1159/000489953 ◽

2018 ◽

Vol 47 (1) ◽

pp. 414-427 ◽

Cited By ~ 9

Author(s):

Min Fang ◽

Wencheng Huang ◽

Dan Mo ◽

Wei Zhao ◽

Rongyong Huang

Keyword(s):

Cancer Risk ◽

Head And Neck ◽

Cancer Susceptibility ◽

Cytotoxic T Lymphocyte ◽

Meta Analysis ◽

Asian Population ◽

Cancer Type ◽

Case Control Studies ◽

Pancreatic Cancers ◽

Increased Risk

Background/Aims: CTLA-4 polymorphisms are associated with susceptibility to various cancers, but the results are often conflicting. Hence, we performed a comprehensive meta-analysis to quantitatively investigate the association between CTLA-4 polymorphisms (rs231775, rs4553808，rs5742909, rs3087243 or rs733618) and cancer risk. Methods: Data were collected from PubMed and Web of Science. A total of 67 case-control studies were selected for quantitative analysis. Stata (Version 12) software was used to calculate the odds ratio (OR) and 95% confidence interval (CI) to evaluate the strength of the associations. Subgroup meta-analysis was conducted based on ethnicity and cancer type. Heterogeneity tests, sensitivity analysis, and publication bias assessments were also performed. Results: rs231775, rs4553808 and rs5742909 but not rs3087243 and rs733618 were significantly related to cancer risk. In analyses stratified by ethnicity, both rs231775 and rs4553808 were significant susceptibility polymorphisms in an Asian population but not in a Caucasian population. Moreover, there were stronger associations between the rs231775 polymorphism and increased risk of bone, breast, liver, head and neck and pancreatic cancers. Additionally, rs4553808 was associated with significantly increased susceptibility to breast cancer and head and neck cancer. Conclusion: rs231775, rs4553808 and rs5742909 may be used as predictive genetic biomarkers for cancer predisposition. Combined detection of CTLA-4 SNPs could be a useful tool for prediction of cancer susceptibility in clinical practice.

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Relevance of hMLH1 -93G>A, 655A>G and 1151T>A polymorphisms with colorectal cancer susceptibility: a meta-analysis based on 38 case-control studies

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.64.10.942 ◽

2018 ◽

Vol 64 (10) ◽

pp. 942-951 ◽

Cited By ~ 1

Author(s):

Mohammad Zare ◽

Jamal Jafari-Nedooshan ◽

Mohammadali Jafari ◽

Hossein Neamatzadeh ◽

Seyed Mojtaba Abolbaghaei ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Susceptibility ◽

Meta Analysis ◽

Asian Population ◽

Case Control ◽

Biomedical Literature ◽

Case Control Studies ◽

Increased Risk ◽

Comprehensive Search ◽

Meta Analyses

SUMMARY OBJECTIVE: There has been increasing interest in the study of the association between human mutL homolog 1 (hMLH1) gene polymorphisms and risk of colorectal cancer (CRC). However, results from previous studies are inconclusive. Thus, a meta-analysis was conducted to derive a more precise estimation of the effects of this gene. METHODS: A comprehensive search was conducted in the PubMed, EMBASE, Chinese Biomedical Literature databases until January 1, 2018. Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. RESULTS: Finally, 38 case-control studies in 32 publications were identified met our inclusion criteria. There were 14 studies with 20668 cases and 19533 controls on hMLH1 −93G>A, 11 studies with 5,786 cases and 8,867 controls on 655A>G and 5 studies with 1409 cases and 1637 controls on 1151T>A polymorphism. The combined results showed that 655A>G and 1151T>A polymorphisms were significantly associated with CRC risk, whereas −93G>A polymorphism was not significantly associated with CRC risk. As for ethnicity, −93G>A and 655A>G polymorphisms were associated with increased risk of CRC among Asians, but not among Caucasians. More interestingly, subgroup analysis indicated that 655A>G might raise CRC risk in PCR-RFLP and HB subgroups. CONCLUSION: Inconsistent with previous meta-analyses, this meta-analysis shows that the hMLH1 655A>G and 1151T>A polymorphisms might be risk factors for CRC. Moreover, the −93G>A polymorphism is associated with the susceptibility of CRC in Asian population.

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Oral Contraceptive Use and Breast Cancer Risk Assessment: A Systematic Review and Meta-Analysis of Case-Control Studies, 2009–2020

Cancers ◽

10.3390/cancers13225654 ◽

2021 ◽

Vol 13 (22) ◽

pp. 5654

Author(s):

Agnieszka Barańska ◽

Agata Błaszczuk ◽

Wiesław Kanadys ◽

Maria Malm ◽

Katarzyna Drop ◽

...

Keyword(s):

Breast Cancer ◽

Oral Contraceptive ◽

Cancer Risk ◽

Meta Analysis ◽

Case Control ◽

Cochrane Library ◽

Control Group ◽

Case Control Studies ◽

Increased Risk ◽

Breast Cancer Risk Assessment

To perform a meta-analysis of case-control studies that addressed the association between oral contraceptive pills (OC) use and breast cancer (BrCa), PubMED (MEDLINE), Embase, and the Cochrane Library were searched to identify case-control studies of OC and BrCa published between 2009 and 2020. We used the DerSimonian–Laird method to compute pooled odds ratios (ORs) and confidence intervals (CIs), and the Mantel–Haenszel test to assess the association between OC use and cancer. Forty-two studies were identified that met the inclusion criteria and we included a total of 110,580 women (30,778 into the BrCa group and 79,802 into the control group, of which 15,722 and 38,334 were using OC, respectively). The conducted meta-analysis showed that the use of OC was associated with a significantly increased risk of BrCa in general, OR = 1.15, 95% CI: 1.01 to 1.31, p = 0.0358. Regarding other risk factors for BrCa, we found that increased risk was associated significantly with early menarche, nulliparous, non-breastfeeding, older age at first parity, postmenopause, obesity, smoking, and family history of BrCa. Despite our conclusion that birth control pills increase the cancer risk being supported by extensive previous studies and meta-analyzes, further confirmation is required.

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COVID-19 Mortality is Associated with Impaired Innate Immunity in Pre-existing Health Conditions

10.1101/2021.05.31.446476 ◽

2021 ◽

Author(s):

Matthew E Lee ◽

Yung Chang ◽

Navid Ahmadinejad ◽

Crista E Johnson-Agbakwu ◽

Celeste Bailey ◽

...

Keyword(s):

Risk Factors ◽

Innate Immunity ◽

Viral Infections ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Therapeutic Interventions ◽

Health Conditions ◽

Molecular Abnormalities ◽

Hazard Ratios ◽

Increased Risk

Background: COVID-19 poses a life-threatening endangerment to individuals with chronic diseases. However, not all comorbidities affect COVID-19 prognosis equally. Some increase the risk of COVID-19 related death by more than six folds while others show little to no impact. To prevent severe outcomes, it is critical that we comprehend pre-existing molecular abnormalities in common health conditions that predispose patients to poor prognoses. In this study, we aim to discover some of these molecular risk factors by associating gene expression dysregulations in common health conditions with COVID-19 mortality rates in different cohorts. Methods: We focused on fourteen pre-existing health conditions, for which age-and-sex-adjusted hazard ratios of COVID-19 mortality have been documented. For each health condition, we analyzed existing transcriptomics data to identify differentially expressed genes (DEGs) between affected individuals and unaffected individuals. We then tested if fold changes of any DEG in these pre-existing conditions were correlated with hazard ratios of COVID-19 mortality to discover molecular risk factors. We performed gene set enrichment analysis to identify functional groups overrepresented in these risk factor genes and examined their relationships with the COVID-19 disease pathway. Results: We found that upregulated expression of 70 genes and downregulated expression of 181 genes in pre-existing health conditions were correlated with increased risk of COVID-19 related death. These genes were significantly enriched with endoplasmic reticulum (ER) function, proinflammatory reaction, and interferon production that participate in viral transcription and immune responses to viral infections. Conclusions: Impaired innate immunity in pre-existing health conditions are associated with increased hazard of COVID-19 mortality. The discovered molecular risk factors are potential prognostic biomarkers and targets for therapeutic interventions.

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Tumor Expression Profile Analysis Developed and Validated a Prognostic Model Based on Immune-Related Genes in Bladder Cancer

Frontiers in Genetics ◽

10.3389/fgene.2021.696912 ◽

2021 ◽

Vol 12 ◽

Author(s):

Bingqi Dong ◽

Jiaming Liang ◽

Ding Li ◽

Wenping Song ◽

Shiming Zhao ◽

...

Keyword(s):

Bladder Cancer ◽

Regression Analysis ◽

Malignant Tumors ◽

Immune Therapy ◽

Enrichment Analysis ◽

R Package ◽

Gene Set Enrichment Analysis ◽

Lasso Regression ◽

Potential Biomarker ◽

Immune Related Genes

Background: Bladder cancer (BLCA) ranks 10th in incidence among malignant tumors and 6th in incidence among malignant tumors in males. With the application of immune therapy, the overall survival (OS) rate of BLCA patients has greatly improved, but the 5-year survival rate of BLCA patients is still low. Furthermore, not every BLCA patient benefits from immunotherapy, and there are a limited number of biomarkers for predicting the immunotherapy response. Therefore, novel biomarkers for predicting the immunotherapy response and prognosis of BLCA are urgently needed.Methods: The RNA sequencing (RNA-seq) data, clinical data and gene annotation files for The Cancer Genome Atlas (TCGA) BLCA cohort were extracted from the University of California, Santa Cruz (UCSC) Xena Browser. The BLCA datasets GSE31684 and GSE32894 from the Gene Expression Omnibus (GEO) database were extracted for external validation. Immune-related genes were extracted from InnateDB. Significant differentially expressed genes (DEGs) were identified using the R package “limma,” and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for the DEGs were performed using R package “clusterProfiler.” Least absolute shrinkage and selection operator (LASSO) regression analysis were used to construct the signature model. The infiltration level of each immune cell type was estimated using the single-sample gene set enrichment analysis (ssGSEA) algorithm. The performance of the model was evaluated with receiver operating characteristic (ROC) curves and calibration curves.Results: In total, 1,040 immune-related DEGs were identified, and eight signature genes were selected to construct a model using LASSO regression analysis. The risk score of BLCA patients based on the signature model was negatively correlated with OS and the immunotherapy response. The ROC curve for OS revealed that the model had good accuracy. The calibration curve showed good agreement between the predictions and actual observations.Conclusions: Herein, we constructed an immune-related eight-gene signature that could be a potential biomarker to predict the immunotherapy response and prognosis of BLCA patients.

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The Role of Circular RNA CDR1as/ciRS-7 in Regulating Tumor Microenvironment: A Pan-Cancer Analysis

Biomolecules ◽

10.3390/biom9090429 ◽

2019 ◽

Vol 9 (9) ◽

pp. 429 ◽

Cited By ~ 24

Author(s):

Zou ◽

Zheng ◽

Deng ◽

Yang ◽

Xie ◽

...

Keyword(s):

Tumor Microenvironment ◽

Signaling Pathway ◽

Malignant Tumors ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Circular Rna ◽

Gene Set Enrichment Analysis ◽

Functional Enrichment ◽

Receptor Interaction

Circular RNA CDR1as/ciRS-7 functions as an oncogenic regulator in various cancers. However, there has been a lack of systematic and comprehensive analysis to further elucidate its underlying role in cancer. In the current study, we firstly performed a bioinformatics analysis of CDR1as among 868 cancer samples by using RNA-seq datasets of the MiOncoCirc database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), CIBERSORT, Estimating the Proportion of Immune and Cancer cells (EPIC), and the MAlignant Tumors using Expression data (ESTIMATE) algorithm were applied to investigate the underlying functions and pathways. Functional enrichment analysis suggested that CDR1as has roles associated with angiogenesis, extracellular matrix (ECM) organization, integrin binding, and collagen binding. Moreover, pathway analysis indicated that it may regulate the TGF-β signaling pathway and ECM-receptor interaction. Therefore, we used CIBERSORT, EPIC, and the ESTIMATE algorithm to investigate the association between CDR1as expression and the tumor microenvironment. Our data strongly suggest that CDR1as may play a specific role in immune and stromal cell infiltration in tumor tissue, especially those of CD8+ T cells, activated NK cells, M2 macrophages, cancer-associated fibroblasts (CAFs) and endothelial cells. Generally, systematic and comprehensive analyses of CDR1as were conducted to shed light on its underlying pro-cancerous mechanism. CDR1as regulates the TGF-β signaling pathway and ECM-receptor interaction to serve as a mediator in alteration of the tumor microenvironment.

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Association of miRNA biosynthesis genes DROSHA and DGCR8 polymorphisms with cancer susceptibility: a systematic review and meta-analysis

Bioscience Reports ◽

10.1042/bsr20180072 ◽

2018 ◽

Vol 38 (3) ◽

Cited By ~ 4

Author(s):

Jing Wen ◽

Zhi Lv ◽

Hanxi Ding ◽

Xinxin Fang ◽

Mingjun Sun

Keyword(s):

Cancer Risk ◽

Genetic Model ◽

Cancer Susceptibility ◽

Meta Analysis ◽

Population Based ◽

Nucleotide Polymorphisms ◽

Case Control Studies ◽

Exclusion Criteria ◽

Single Nucleotide ◽

Stratified Analysis

Single nucleotide polymorphisms (SNPs) in miRNA biosynthesis genes DROSHA and DGCR8 were indicated to be correlated with cancer risk. We comprehensively reviewed and analyzed the effect of DROSHA and DGCR8 polymorphisms on cancer risk. Eligible articles were selected according to a series of inclusion and exclusion criteria. Consequently, ten case–control studies (from nine citations) with 4265 cancer cases and 4349 controls were involved in a meta-analysis of seven most prevalent SNPs (rs10719 T/C, rs6877842 G/C, rs2291109 A/T, rs642321 C/T, rs3757 G/A, rs417309 G/A, rs1640299 T/G). Our findings demonstrated that the rs417309 SNP in DGCR8 was significantly associated with an elevated risk of overall cancer in every genetic model. In stratified analysis, correlations of DROSHA rs10719 and rs6877842 SNPs were observed in Asian and laryngeal cancer subgroups, respectively. Moreover, associations of the rs417309 SNP could also be found in numerous subgroups including: Asian and Caucasian population subgroups; laryngeal and breast cancer subgroups; population-based (PB) and hospital-based (HB) subgroups. In conclusion, the DROSHA rs10719, rs6877842 SNPs, and DGCR8 rs417309 SNP play pivotal roles in cancerogenesis and may be potential biomarkers for cancer-forewarning.

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Diet and cancer in Mediterranean countries: carbohydrates and fats

Public Health Nutrition ◽

10.1017/s1368980009990425 ◽

2009 ◽

Vol 12 (9A) ◽

pp. 1595-1600 ◽

Cited By ~ 39

Author(s):

Cristina Bosetti ◽

Claudio Pelucchi ◽

Carlo La Vecchia

Keyword(s):

Cancer Risk ◽

Olive Oil ◽

Digestive Tract ◽

Mediterranean Diet ◽

A Priori ◽

Glycaemic Index ◽

Case Control Studies ◽

Mediterranean Countries ◽

Increased Risk ◽

The Mediterranean

AbstractObjectiveSeveral aspects of the diet characteristic of the Mediterranean countries are considered favourable not only on cardiovascular disease, but also on cancer risk. We considered some aspects of the Mediterranean diet (including, in particular, the consumption of olive oil and carbohydrates) on cancer risk.Design, Setting and SubjectsData were derived from a series of case-control studies, conducted in Italy since the early 1990s, on over 10 000 cases of thirteen cancer sites and over 17 000 controls.ResultsOlive oil, and other mono- and unsaturated fats, appear to be favourable indicators of breast, ovarian, colorectal, but mostly of upper aero-digestive tract cancers. Whole grain foods are also related to reduced risk of upper aero-digestive tract and various other cancers. In contrast, refined grain intake and, consequently, glycaemic index and glycaemic load were associated to increased risk for several cancer sites. Fish, and hence a diet rich in n-3 polyunsaturated fatty acids, tended to be another favourable diet indicator, while frequent red meat intake was directly related to some common neoplasms. An a priori defined Mediterranean diet score was inversely related to upper digestive and respiratory tract cancers.ConclusionsThese data provide additional evidence that major characteristics of the Mediterranean diet favourably affect cancer risk.

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