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Singh RD, Dholariya S, Shekher A, Avadhesh, Parchwani D, Gupta SC. Role of IL-1 gene polymorphisms in common solid cancers. MULTIFACETED ROLE OF IL-1 IN CANCER AND INFLAMMATION 2023:1-69. [DOI: 10.1016/b978-0-12-824273-5.00002-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Cheng KJ, Mejia Mohammed EH, Khong TL, Mohd Zain S, Thavagnanam S, Ibrahim ZA. IL-1α and colorectal cancer pathogenesis: Enthralling candidate for anti-cancer therapy. Crit Rev Oncol Hematol 2021; 163:103398. [PMID: 34147647 DOI: 10.1016/j.critrevonc.2021.103398] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 06/08/2021] [Accepted: 06/09/2021] [Indexed: 01/04/2023] Open
Abstract
Inflammation has been well-established as a hallmark of colorectal cancer (CRC). Interleukin-1 alpha (IL-1α) is one of the primary inflammatory mediators driving the pathogenesis of inflammation-associated CRC. This systematic review presents the roles of IL-1α in the pathogenesis of the disease. Bibliographic databases PubMed, Science Direct, Scopus and Web of Science were systematically searched for articles that addresses the relationship between IL-1α and colorectal cancer. We highlighted various mechanisms by which IL-1α promotes the pathogenesis of CRC including enhancement of angiogenesis, metastasis, resistance to therapy, and inhibition of tumour suppressive genes. We also discussed the potential mechanisms by which IL-1α expression is induced or secreted in various studies. Beyond these, the systematic review also highlights several potential therapeutic strategies which should be further explored in the future; to target IL-1α and/or its associated pathways; paving our way in finding effective treatments for CRC patients.
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Affiliation(s)
- Kim Jun Cheng
- Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | | | - Tak Loon Khong
- Department of Surgery, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Shamsul Mohd Zain
- Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Surendran Thavagnanam
- Department of Paediatrics, Royal London Hospital, Whitechapel Rd, Whitechapel, E1 1FR London, United Kingdom
| | - Zaridatul Aini Ibrahim
- Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia.
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Karami S, Sarabandi S, Pourzand P, Tabasi F, Hashemi M, Bahari G. Lack of association between 4-base pair insertion/deletion (rs3783553) polymorphism within the 3′UTR of IL1A and breast cancer: A preliminary report. GENE REPORTS 2021. [DOI: 10.1016/j.genrep.2021.101067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Xia H, Chen Y, Meng J, Liang C. Effect of polymorphism on IL1A to cancer susceptibility: Evidence based on 34,016 subjects. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2019; 47:3138-3152. [PMID: 31359795 DOI: 10.1080/21691401.2019.1646750] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Haoran Xia
- Department of Urology, the First Affiliated Hospital of Anhui Medical University; Institute of Urology and Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, China
| | - Yiding Chen
- The First Clinical College of Anhui Medical University, Hefei, Anhui, China
| | - Jialin Meng
- Department of Urology, the First Affiliated Hospital of Anhui Medical University; Institute of Urology and Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, China
| | - Chaozhao Liang
- Department of Urology, the First Affiliated Hospital of Anhui Medical University; Institute of Urology and Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, China
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Ji H, Lu L, Huang J, Liu Y, Zhang B, Tang H, Sun D, Zhang Y, Shang H, Li Y, Lu H. IL1A polymorphisms is a risk factor for colorectal cancer in Chinese Han population: a case control study. BMC Cancer 2019; 19:181. [PMID: 30819119 PMCID: PMC6394039 DOI: 10.1186/s12885-019-5395-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Accepted: 02/20/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most common cancers worldwide, and genetic variations exert distinct roles in its pathogenesis. Single nucleotide polymorphisms (SNPs) in interleukin 1 alpha (IL1A) were reported to be correlated to the susceptibility of diverse cancers. The aim of this study was to assess the association of IL1A SNPs with the risk of colorectal cancer in a Chinese Han population. METHODS To evaluate the correlation between IL1A polymorphisms and CRC risk, Agena MassARRAY platform was used for genotype determination among 248 CRC patients and 463 controls. The relationships between IL1A variants and CRC susceptibility were examined by logistic regression analysis. Stratified analysis was conducted for the association detection in males and females. Haplotype construction and analysis were applied to evaluate the potential relationship between the genetic block and the risk of CRC. SNP functional exploration was performed with available bioinformatics datasets. RESULTS After adjusting for age and gender, the "AA" genotype of rs2856838 exhibited a risk association with colorectal cancer in the recessive model (adjusted OR = 1.98, 95% CI: 1.05-3.72, p = 0.036). With stratified analysis, the recessive models of rs3783550 (OR = 2.17, 95% CI: 1.03-4.60, p = 0.043), rs2856838 (OR = 2.58, 95% CI: 1.13-5.87, p = 0.024), rs1609682 (OR = 2.20, 95% CI: 1.04-4.65, p = 0.040), and rs3783521 (OR = 2.13, 95% CI: 1.01-4.49, p = 0.048) revealed significant relationships between these variants and an increased CRC risk only in females. Bioinformatics analysis also revealed the putative functions of the selected SNPs. CONCLUSIONS This study demonstrated that rs2856838 could influence the susceptibility to CRC in Chinese Han population from northwest China. IL1A variants rs3783550, rs2856838, rs1609682, and rs3783521 were associated with CRC risk only in females.
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Affiliation(s)
- Hong Ji
- Department of General Surgery, The Second Affiliated Hospital, Xi’an Jiaotong University School of Medicine, #157, West fifth Road, Xi’an, 710004 Shaanxi People’s Republic of China
| | - Le Lu
- Department of General Surgery, The Second Affiliated Hospital, Xi’an Jiaotong University School of Medicine, #157, West fifth Road, Xi’an, 710004 Shaanxi People’s Republic of China
| | - Jingjing Huang
- Department of General Surgery, The Second Affiliated Hospital, Xi’an Jiaotong University School of Medicine, #157, West fifth Road, Xi’an, 710004 Shaanxi People’s Republic of China
| | - Yang Liu
- Department of Surgery, The People’s Hospital of Zhenba Country, Hanzhong, 723600 Shaanxi People’s Republic of China
| | - Binchao Zhang
- Department of General Surgery, The People’s Hospital of Shangzhou District, Shangluo, 726000 Shaanxi People’s Republic of China
| | - Hui Tang
- Department of General Surgery, The Second Affiliated Hospital, Xi’an Jiaotong University School of Medicine, #157, West fifth Road, Xi’an, 710004 Shaanxi People’s Republic of China
| | - Dangze Sun
- Department of General Surgery, The Second Affiliated Hospital, Xi’an Jiaotong University School of Medicine, #157, West fifth Road, Xi’an, 710004 Shaanxi People’s Republic of China
| | - Yafei Zhang
- Department of General Surgery, The Second Affiliated Hospital, Xi’an Jiaotong University School of Medicine, #157, West fifth Road, Xi’an, 710004 Shaanxi People’s Republic of China
| | - Hao Shang
- Department of General Surgery, The Second Affiliated Hospital, Xi’an Jiaotong University School of Medicine, #157, West fifth Road, Xi’an, 710004 Shaanxi People’s Republic of China
| | - Yiming Li
- Department of General Surgery, The Second Affiliated Hospital, Xi’an Jiaotong University School of Medicine, #157, West fifth Road, Xi’an, 710004 Shaanxi People’s Republic of China
| | - Hongwei Lu
- Department of General Surgery, The Second Affiliated Hospital, Xi’an Jiaotong University School of Medicine, #157, West fifth Road, Xi’an, 710004 Shaanxi People’s Republic of China
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Hashemi M, Tabasi F, Bahari G, Taheri M, Ansari H. An updated meta-analysis on the association between 4-bp insertion/deletion (rs3783553) polymorphism within the 3`UTR of IL1A and the risk of cancer. GENE REPORTS 2018. [DOI: 10.1016/j.genrep.2018.06.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Ma Q, Mao Z, Du J, Liao S, Zheng Y, Zhi M, Zhang J, Wang Y. Association between an insertion/deletion polymorphism in the interleukin-1α gene and the risk of colorectal cancer in a Chinese population. Int J Biol Markers 2018; 33:1724600818785069. [PMID: 30016900 DOI: 10.1177/1724600818785069] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Previous studies have reported that polymorphisms in the interleukin-1 gene may be involved in tumorigenesis and tumor progression. AIM The purpose of the present study was to evaluate whether an insertion/deletion polymorphism, rs3783553, located in the miR-122 target gene interleukin-1α, was associated with the risk of colorectal cancer. METHODS Genomic DNA was extracted from peripheral venous blood of 382 patients with colorectal cancer and 433 controls, and the polymorphism was genotyped using a polymerase chain reaction assay. RESULTS Significantly decreased colorectal cancer risk was observed to be associated with the interleukin-1α rs3783553 insertion/insertion genotype ( P=0.0001; OR=0.41; 95% CI 0.26, 0.65) and the insertion allele ( P<0.001; OR=0.68; 95% CI 0.55, 0.83). Stratification analysis based on clinical and pathological features also revealed that the "TTCA" insertion allele of rs3783553 contributes to slow the progression of colorectal cancer. CONCLUSION These results suggest that the rs3783553 polymorphism could be a useful genetic marker to predict the size/extent of colorectal cancer.
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Affiliation(s)
- Qizhao Ma
- 1 West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, P.R. China
| | - Zhigang Mao
- 2 Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China
| | - Jipei Du
- 1 West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, P.R. China
| | - Shiping Liao
- 1 West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, P.R. China
| | - Yanjiang Zheng
- 1 West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, P.R. China
| | - Maohui Zhi
- 1 West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, P.R. China
| | - Ji Zhang
- 1 West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, P.R. China
| | - Yufang Wang
- 1 West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, P.R. China
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Wang C, Sturgis EM, Chen X, Wei Q, Li G. A functional variant at miRNA-122 binding site in IL-1a 3' UTR predicts risk of recurrence in patients with oropharyngeal cancer. Oncotarget 2018; 7:34472-9. [PMID: 27121322 PMCID: PMC5085169 DOI: 10.18632/oncotarget.8908] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Accepted: 04/07/2016] [Indexed: 12/16/2022] Open
Abstract
IL-1α, an important regulator of immune and inflammation responses, has been implicated in cancer development and prognosis. An insertion (Ins)/deletion (Del) polymorphism (IL-1α rs3783553) in the 3′ UTR of IL-1α may disrupt a binding site for miRNA-122 and may affect its transcription level. Thus, this polymorphism may cause interindividual variation in immune and inflammation responses and thus may lead to different susceptibility to treatment response and prognosis of such patients. We evaluated the association of IL-1α rs3783553 polymorphism with risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP) in a cohort of 1008 patients. Log-rank test and univariate and multivariable Cox models were used to evaluate associations. Compared with patients with Del/Del homozygous genotype, the patients with Ins/Del+Ins/Ins variant genotypes had worse disease-free survival (log-rank P < 0.0001) and increased risk of SCCOP recurrence (HR, 2.4, 95% CI, 1.7-3.3) after multivariable adjustment. Furthermore, among patients with HPV16-positive tumors, the patients with Ins/Del+Ins/Ins variant genotypes of the IL-1α polymorphism had worse disease-free survival (log-rank P < 0.0001) and much higher recurrence risk than those with Del/Del homozygous genotype of this polymorphism (HR, 16.3, 95% CI, 5.0-52.7). Our findings suggest that IL-1α rs3783553 polymorphism may modulate the risk of SCCOP recurrence in patients, particularly for patients with HPV16-positive tumors. However, larger studies are needed to validate these results.
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Affiliation(s)
- Chengyuan Wang
- Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.,Department of Otolaryngology-Head and Neck Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Erich M Sturgis
- Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.,Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Xingming Chen
- Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.,Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Qingyi Wei
- Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA
| | - Guojun Li
- Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.,Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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Cavalcante GC, Amador MAT, Ribeiro dos Santos AM, Carvalho DC, Andrade RB, Pereira EEB, Fernandes MR, Costa DF, Santos NPC, Assumpção PP, Ribeiro dos Santos Â, Santos S. Analysis of 12 variants in the development of gastric and colorectal cancers. World J Gastroenterol 2017; 23:8533-8543. [PMID: 29358861 PMCID: PMC5752713 DOI: 10.3748/wjg.v23.i48.8533] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Revised: 10/25/2017] [Accepted: 11/07/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the relation between 12 polymorphisms and the development of gastric cancer (GC) and colorectal cancer (CRC).
METHODS In this study, we included 125 individuals with GC diagnosis, 66 individuals with CRC diagnosis and 475 cancer-free individuals. All participants resided in the North region of Brazil and authorized the use of their samples. The 12 polymorphisms (in CASP8, CYP2E1, CYP19A1, IL1A, IL4, MDM2, NFKB1, PAR1, TP53, TYMS, UGT1A1 and XRCC1 genes) were genotyped in a single PCR for each individual, followed by fragment analysis. To avoid misinterpretation due to population substructure, we applied a previously developed set of 61 ancestry-informative markers that can also be genotyped by multiplex PCR. The statistical analyses were performed in Structure v.2.3.4, R environment and SPSS v.20.
RESULTS After statistical analyses with the control of confounding factors, such as genetic ancestry, three markers (rs79071878 in IL4, rs3730485 in MDM2 and rs28362491 in NFKB1) were positively associated with the development of GC. One of these markers (rs28362491) and the marker in the UGT1A1 gene (rs8175347) were positively associated with the development of CRC. Therefore, we investigated whether the joint presence of the deleterious alleles of each marker could affect the development of cancer and we obtained positive results in all analyses. Carriers of the combination of alleles RP1 + DEL (rs79071878 and rs28361491, respectively) are at 10-times greater risk of developing GC than carriers of other combinations. Similarly, carriers of the combination of DEL + RARE (rs283628 and rs8175347) are at about 12-times greater risk of developing CRC than carriers of other combinations.
CONCLUSION These findings are important for the comprehension of gastric and CRC development, particularly in highly admixed populations, such as the Brazilian population.
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Affiliation(s)
- Giovanna C Cavalcante
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66075-970, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Marcos AT Amador
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66075-970, Brazil
| | | | - Darlen C Carvalho
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66075-970, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Roberta B Andrade
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66075-970, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Esdras EB Pereira
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Marianne R Fernandes
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Danielle F Costa
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Ney PC Santos
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66075-970, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Paulo P Assumpção
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Ândrea Ribeiro dos Santos
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66075-970, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
| | - Sidney Santos
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66075-970, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Brazil
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Abdel-Hamed AR, Ghattas MH, Mesbah NM, Saleh SM, Abo-Elmatty DM. Association of interleukin-1A insertion/deletion gene polymorphism and possible high risk factors with non-alcoholic fatty liver disease in Egyptian patients. Arch Physiol Biochem 2017. [PMID: 28627263 DOI: 10.1080/13813455.2017.1339717] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
CONTEXT Interleukin-1A (IL-1A) is a cytokine involved in inflammatory process. IL-1A (rs3783553) gene polymorphism is comprised in the regulation of IL-1A expression. OBJECTIVE This study aims to evaluate association of IL-1A (I/D) gene polymorphism with NAFLD and its component traits among Egyptian populations. METHODS The study included 75 healthy subjects and 75 patients with NAFLD. Different genotypes of IL-1A (I/D) gene polymorphism were determined by PCR-PAGE technique, serum IL-1A level and other biochemical parameters were measured. RESULTS The major D allele was significantly associated with NAFLD patients (p = .002). DD genotype showed a significant increase in BMI and decrease in HDL-C. Also serum IL-1A was significantly correlated with the DD genotype. Serum IL-1A showed a significant positive correlation with BMI, triglycerides, total cholesterol, LDL-C, VLDL-C and FBG, and a significant negative correlation with HDL-C. CONCLUSIONS Major D allele of IL-1A (I/D) gene polymorphism is associated with NAFLD in the Egyptian population.
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Affiliation(s)
- Asmaa R Abdel-Hamed
- a Department of Biochemistry, Faculty of Pharmacy , Suez Canal University , Ismailia , Egypt
| | - Maivel H Ghattas
- b Department of Medical Biochemistry, Faculty of Medicine , Port Said University , Port Said , Egypt
| | - Noha M Mesbah
- a Department of Biochemistry, Faculty of Pharmacy , Suez Canal University , Ismailia , Egypt
| | - Samy M Saleh
- a Department of Biochemistry, Faculty of Pharmacy , Suez Canal University , Ismailia , Egypt
| | - Dina M Abo-Elmatty
- a Department of Biochemistry, Faculty of Pharmacy , Suez Canal University , Ismailia , Egypt
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Abdel-Hamed AR, Mesbah NM, Ghattas MH, Abo-elmatty DM, Saleh SM. Serum miRNA-122 expression in non-alcoholic fatty liver disease among Egyptian patients and its correlation with interleukin-1A gene polymorphism. Meta Gene 2017. [DOI: 10.1016/j.mgene.2017.07.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
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12
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Hashemi M, Bahari G, Sarhadi S, Eskandari E, Narouie B, Taheri M, Ghavami S. 4‐bp insertion/deletion (rs3783553) polymorphism within the 3′UTR of IL1A contributes to the risk of prostate cancer in a sample of Iranian population. J Cell Biochem 2017; 119:2627-2635. [DOI: 10.1002/jcb.26427] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2017] [Accepted: 10/10/2017] [Indexed: 12/20/2022]
Affiliation(s)
- Mohammad Hashemi
- Cellular and Molecular Research CenterZahedan University of Medical SciencesZahedanIran
- Department of Clinical Biochemistry, School of MedicineZahedan University of Medical SciencesZahedanIran
| | - Gholamreza Bahari
- Department of Clinical Biochemistry, School of MedicineZahedan University of Medical SciencesZahedanIran
| | - Shamim Sarhadi
- Faculty of Advanced Medical Sciences, Department of Medical BiotechnologyTabriz University of Medical SciencesTabrizIran
| | - Ebrahim Eskandari
- Department of Clinical Biochemistry, School of MedicineZahedan University of Medical SciencesZahedanIran
| | - Behzad Narouie
- Urology and Nephrology Research Center; Department of Urology, Shahid Labbafinejad Medical CenterShahid Beheshti University of Medical SciencesTehranIran
| | - Mohsen Taheri
- Genetics of Non Communicable Disease Research CenterZahedan University of Medical SciencesZahedanIran
| | - Saeid Ghavami
- Department of Human Anatomy and Cell Science, College of Medicine, Faculty of Health SciencesUniversity of ManitobaWinnipegCanada
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Choi WS, Kim O, Yoon JH, Park YG, Nam SW, Lee JY, Park WS. Association of IL-17A/F polymorphisms with the risk of gastritis and gastric cancer in the Korean population. Mol Cell Toxicol 2016; 12:327-336. [DOI: 10.1007/s13273-016-0037-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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14
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Jia ZF, Zhang SL, Cao XY, Zhou BS, Jiang J. Interaction between Helicobacter pylori and host genetic variants in gastric carcinogenesis. Future Oncol 2016; 12:2127-34. [PMID: 27324311 DOI: 10.2217/fon-2016-0233] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Helicobacter pylori (H. pylori) is the definite carcinogen of gastric cancer. H. pylori infection induces chronic inflammation, causes DNA damage and aberrant methylation of genes and these pathways are involved in H. pylori-related gastric carcinogenesis. Polymorphisms of the genes involved in these pathways could alter susceptibility to gastric cancer. In this mini review, we focused on the role of polymorphisms in these genes on the susceptibility to gastric cancer, with a particular emphasis on their possible interactions with H. pylori infection. We found that many studies on this theme did not simultaneously report H. pylori infection and the interactions remained inconclusive.
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Affiliation(s)
- Zhi-Fang Jia
- Division of Clinical Research, First Hospital of Jilin University, Changchun 130021, China.,Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110112, China
| | - Song-Ling Zhang
- Department of Gynecological Oncology, First Hospital of Jilin University, Changchun 130021, China
| | - Xue-Yuan Cao
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun 130021, China
| | - Bao-Sen Zhou
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110112, China
| | - Jing Jiang
- Division of Clinical Research, First Hospital of Jilin University, Changchun 130021, China
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Abstract
PURPOSE Alarmins are constitutively present endogenous molecules that essentially act as early warning signals for the immune system. We provide a brief overview of major alarmins and highlight their roles in tumor immunity. METHODS We searched PubMed up to January 10, 2016, using alarmins and/or damage-associated molecular patterns (DAMPs), as key words. We selected and reviewed articles that focused on the discovery and functions of alarmin and their roles in tumor immunity. FINDINGS Alarmins are essentially endogenous immunostimulatory DAMP molecules that are exposed in response to danger (eg, infection or tissue injury) as a result of degranulation, cell death, or induction. They are sensed by chemotactic receptors and pattern recognition receptors to induce immune responses by promoting the recruitment and activation of leukocytes, particularly antigen-presenting cells. IMPLICATIONS Accumulating data suggest that certain alarmins, High-mobility group nucleosome-binding protein 1 (HMGN1) in particular, contribute to the generation of antitumor immunity. Some alarmins can also be used as cancer biomarkers. Therefore, alarmins can potentially be applied for our fight against cancers.
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Affiliation(s)
- Yingjie Nie
- Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick National Laboratory for Cancer Research, Frederick, Maryland; Guizhou Provincial Peoples' Hospital, Guiyang, Guizhou Province, China
| | - De Yang
- Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick National Laboratory for Cancer Research, Frederick, Maryland; Basic Research Program, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, Maryland
| | - Joost J Oppenheim
- Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick National Laboratory for Cancer Research, Frederick, Maryland.
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Amador MAT, Cavalcante GC, Santos NPC, Gusmão L, Guerreiro JF, Ribeiro-dos-Santos Â, Santos S. Distribution of allelic and genotypic frequencies of IL1A, IL4, NFKB1 and PAR1 variants in Native American, African, European and Brazilian populations. BMC Res Notes 2016; 9:101. [PMID: 26879815 PMCID: PMC4754858 DOI: 10.1186/s13104-016-1906-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Accepted: 02/02/2016] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The inflammatory response plays a key role at different stages of cancer development. Allelic variants of the interleukin 1A (IL1A), interleukin 4 (IL4), nuclear factor kappa B1 (NFKB1) and protease-activated receptor 1 (PAR1) genes may influence not only the inflammatory response but also susceptibility to cancer development. Among major ethnic or continental groups, these polymorphic variants present different allelic frequencies. In admixed populations, such as the Brazilian population, data on distribution of these polymorphisms are limited. Here, we collected samples of cancer-free individuals from the north, northeast, midwest, south and southeast regions of Brazil and from the three main groups that gave rise to the Brazilian population: Native Americans from the Brazilian Amazon, Africans and Europeans. We describe the allelic distributions of four IL1A (rs3783553), IL4 (rs79071878), NFKB1 (rs28362491) and PAR1 (rs11267092) gene polymorphisms, which the literature describes as polymorphisms with a risk of cancer or worse prognosis for cancer. RESULTS The genotypic distribution of the four polymorphisms was statistically distinct between Native Americans, Africans and Europeans. For the allelic frequency of these polymorphisms, the Native American population was the most distinct among the three parental populations, and it included the greatest number of alleles with a risk of cancer or worse prognosis for cancer. The PAR1 gene polymorphism allelic distribution was similar among all Brazilian regions. For the other three markers, the northern region population was statistically distinct from other Brazilian region populations. CONCLUSION The IL1A, IL4, NFKB1 and PAR1 gene polymorphism allelic distributions are homogeneous among the regional Brazilian populations, except for the northern region, which significantly differs from the other four Brazilian regions. Among the parental populations, the Native American population exhibited a higher incidence of alleles with risk of cancer or worse prognosis for cancer, which can indicate greater susceptibility to this disease. These genetic data may be useful for future studies on the association between these polymorphisms and cancer in the investigated populations.
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Affiliation(s)
- Marcos A T Amador
- Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Cidade Universitária Prof. José da Silveira Netto, Rua Augusto Corrêa, 01 - Guamá, Belém, PA, CEP: 66.075-110, Brazil.
| | - Giovanna C Cavalcante
- Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Cidade Universitária Prof. José da Silveira Netto, Rua Augusto Corrêa, 01 - Guamá, Belém, PA, CEP: 66.075-110, Brazil.
| | - Ney P C Santos
- Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Cidade Universitária Prof. José da Silveira Netto, Rua Augusto Corrêa, 01 - Guamá, Belém, PA, CEP: 66.075-110, Brazil.
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Brazil.
| | - Leonor Gusmão
- Laboratório de Diagnóstico por DNA, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
- Instituto de Patologia e Imunologia Molecular, Universidade do Porto, Porto, Portugal.
| | - João F Guerreiro
- Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Cidade Universitária Prof. José da Silveira Netto, Rua Augusto Corrêa, 01 - Guamá, Belém, PA, CEP: 66.075-110, Brazil.
| | - Ândrea Ribeiro-dos-Santos
- Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Cidade Universitária Prof. José da Silveira Netto, Rua Augusto Corrêa, 01 - Guamá, Belém, PA, CEP: 66.075-110, Brazil.
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Brazil.
| | - Sidney Santos
- Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Cidade Universitária Prof. José da Silveira Netto, Rua Augusto Corrêa, 01 - Guamá, Belém, PA, CEP: 66.075-110, Brazil.
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Brazil.
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Zhang J, Shi H, Xue M, Yu Q, Yang L, Zheng S, Zhou C. An insertion/deletion polymorphism in the interleukin-1A 3'untranslated region confers risk for gastric cancer. Cancer Biomark 2016; 16:359-365. [PMID: 26889982 DOI: 10.3233/cbm-160574] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE The aim of the study was to evaluate whether the insertion/deletion polymorphism (rs3783553) locating in the 3' untranslated region (3'UTRs) of IL-1A was related to the risk of gastric cancer (GC) in a Chinese population and explore the possible molecular mechanism. METHODS Genomic DNA was extracted from peripheral venous blood of 519 GC patients and 536 healthy control individuals. The IL-1A rs3783553 polymorphism was genotyped by using a polymerase chain reaction assay. The vectors containing the insertion or deletion allele were constructed, and luciferase assay was used to detect the effect of the polymorphism on the transcriptional activity of IL-1A. RESULTS Strong evidence of association was observed between the IL-1A rs3783553 polymorphism and susceptibility to GC in the study. In addition, the `TTCA' insertion allele of rs3783553 disrupts the binding site for miR-122 and miR-378, thereby increasing transcription of IL-1α in vitro. CONCLUSION These findings suggest that functional polymorphism rs3783553 in IL-1A could contribute to GC susceptibility, possibly or at least partially through affecting the transcriptional activity of IL-1A.
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Ma L, Zhou N. Association between an insertion/deletion polymorphism in IL-1A gene and cancer risk: a meta-analysis. Onco Targets Ther 2015; 9:1-6. [PMID: 26719711 PMCID: PMC4690651 DOI: 10.2147/ott.s95887] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Purpose Previous studies have reported the association of an insertion/deletion (Ins/Del) polymorphism (rs3783553) in the 3′ untranslated region of interleukin-1A (IL-1A) with the risk of cancer, such as oral squamous cell carcinoma, nasopharyngeal carcinoma, and cervical carcinoma. However, the results are still inconsistent. The present meta-analysis aimed to clarify the association of IL-1A rs3783553 polymorphism with cancer risk. Methods All eligible studies were selected from PubMed, Web of Science, and Chinese National Knowledge Infrastructure up to September 2, 2015. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate cancer risk. Results A total of ten case–control studies with 4,514 cases and 6,689 controls were included this meta-analysis. We found that IL-1A rs3783553 polymorphism was significantly associated with cancer risk (Ins/Ins + Ins/Del vs Del/Del: OR =0.79, 95% CI =0.67–0.92; Ins/Ins vs Del/Del: OR =0.61, 95% CI =0.47–0.79; Ins/Ins vs Ins/Del + Del/Del: OR =0.67, 95% CI =0.55–0.83; Ins vs Del: OR =0.81, 95% CI =0.72–0.92). In the stratified analyses, significant effects were found among Asian populations (Ins/Ins + Ins/Del vs Del/Del: OR =0.81, 95% CI =0.69–0.95) and cervical carcinoma (Ins/Ins vs Del/Del: OR =0.51, 95% CI =0.34–0.76; Ins/Ins vs Ins/Del + Del/Del: OR =0.52, 95% CI =0.35–0.78). Conclusion Our meta-analysis suggests that the IL-1A rs3783553 polymorphism contributes to susceptibility to cancer. However, well-designed studies with larger sample sizes are required to verify the results.
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Affiliation(s)
- Ling Ma
- Department of Stomatology, No 454 Hospital, PLA, Nanjing, Jiangsu, People's Republic of China
| | - Ning Zhou
- Department of Anesthesiology, No 454 Hospital, PLA, Nanjing, Jiangsu, People's Republic of China
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Interleukin-16 polymorphisms as new promising biomarkers for risk of gastric cancer. Tumour Biol 2015; 37:2119-26. [PMID: 26346169 DOI: 10.1007/s13277-015-4013-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2015] [Accepted: 08/28/2015] [Indexed: 12/27/2022] Open
Abstract
Gastric cancer (GC) is the second cause of cancer-related death worldwide. Interleukin (IL)-16 has a vital role in the development and homeostasis of the immune system. In the present study, we evaluated an exon variant rs4072111 C/T polymorphism and 3' UTR variant rs1131445 C/T within the miRNA binding with gastric cancer susceptibility in Iranian population. Genomic DNA was isolated from peripheral blood samples according to phenol chloroform extraction. The genotypes of IL-16 polymorphisms rs1131445 T/C and rs4072111 T/C were determined by polymerase chain reaction-restriction fragment length polymorphism method. In this case control study, a total of 256 patients with gastric cancer (238 cases (92.9 %) non-cardia and 18 cases (7.1 %) cardia) and 300 healthy control subjects were evaluated. In the present study, we found a significant association between rs4072111 of IL-16 gene and risk of GC in Iranian population. Individuals with CT genotype showed a significant association with 1.79-fold increased risk of GC (P = 0.008; adjusted OR 1.792; 95 % CI 1.164-2.759). The significant association was also detected for T allele of rs4072111 and increased risk of GC (P < 0.001; adjusted OR 1.981; 95 % CI 1.354-2.900). We also observed statistically a significant relationship between rs1131445 of IL-16 CT genotype and GC risk. Carriers of IL-16 CT genotype compared with TT genotype had 1.44 times higher increased likelihood of GC (P = 0.048; adjusted OR 1.445; 95 % CI 1.003-2.084). After stratification according to gender, we observed that in rs1131445, CT and CC male carriers had a higher risk of GC than females (P = 0.08; adjusted OR 1.608; 95 % CI 0.945-2.737 and P = 0.08; adjusted OR 2.186; 95 % CI 0.897-5.325, respectively). We also observed that for male carriers with C allele in rs1131445, there was a 1.53-fold higher risk of GC risk than female subjects (P = 0.029; adjusted OR 1.53; 95 % CI 1.04.4-2.248). We found that the rs1131445 T/C and rs4072111 T/C variants of IL-16 were significantly associated with increased risk of GC in Iranian population.
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Carvalho DC, Wanderley AV, Amador MAT, Fernandes MR, Cavalcante GC, Pantoja KBCC, Mello FAR, de Assumpção PP, Khayat AS, Ribeiro-Dos-Santos Â, Santos S, Dos Santos NPC. Amerindian genetic ancestry and INDEL polymorphisms associated with susceptibility of childhood B-cell Leukemia in an admixed population from the Brazilian Amazon. Leuk Res 2015; 39:S0145-2126(15)30361-1. [PMID: 26321572 DOI: 10.1016/j.leukres.2015.08.008] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2015] [Revised: 07/14/2015] [Accepted: 08/15/2015] [Indexed: 12/29/2022]
Abstract
Acute lymphoblastic leukemia (ALL) is a malignant tumor common in children. Studies of genetic susceptibility to cancer using biallelic insertion/deletion (INDEL) type polymorphisms associated with cancer development pathways may help to clarify etymology of ALL. In this study, we investigate the role of eight functional INDEL polymorphisms and influence of genetic ancestry to B-cell ALL susceptibility in children of Brazilian Amazon population, which has a high degree of inter-ethnic admixture. Ancestry analysis was estimated using a panel of 48 autosomal ancestry informative markers. 130 B-cell ALL patients and 125 healthy controls were included in this study. The odds ratios and 95% confidence intervals were adjusted for confounders. The results indicated an association between the investigated INDEL polymorphisms in CASP8 (rs3834129), CYP19A1 (rs11575899) e XRCC1 (rs3213239) genes in the development of B-cell ALL. The carriers of Insertion/Insertion (Ins/Ins) genotype of the polymorphism in CASP8 gene presented reduced chances of developing B-cell ALL (P=0.001; OR=0.353; 95% CI=0.192-0.651). The Deletion/Deletion (Del/Del) genotype of the polymorphism in CYP19A1 gene was associated to a lower chance of developing B-cell ALL (P=3.35×10-6; OR=0.121; 95% CI=0.050-0.295), while Del/Del genotype of the polymorphism in XRCC1 gene was associated to a higher chance of developing B-cell ALL (P=2.01×10-4; OR=6.559; 95% CI=2.433-17.681). We also found that Amerindian ancestry correlates with the risk of B-cell ALL. For each increase of 10% in the Amerindian ancestry results in 1.4-fold chances of developing B-cell ALL (OR=1.406; 95% IC=1.123-1.761), while each increase of 10% in the European ancestry presents a protection effect in the development of B-cell ALL (OR=0.666; 95% IC=0.536-0.827). The results suggest that genetic factors influence leukemogenesis and might be explored in the stratification of B-cell ALL risk in admixed populations.
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Affiliation(s)
- Darlen C Carvalho
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Belém, Pará, PA, Brazil.
| | - Alayde V Wanderley
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Hospital Ophir Loyola, Departamento de Pediatria, Belém, Pará, PA, Brazil.
| | - Marcos A T Amador
- Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Belém, Pará, PA, Brazil.
| | - Marianne R Fernandes
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Belém, Pará, PA, Brazil.
| | - Giovanna C Cavalcante
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Belém, Pará, PA, Brazil.
| | - Karla B C C Pantoja
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Belém, Pará, PA, Brazil.
| | - Fernando A R Mello
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil.
| | - Paulo P de Assumpção
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA, Brazil.
| | - André S Khayat
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil.
| | - Ândrea Ribeiro-Dos-Santos
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Belém, Pará, PA, Brazil.
| | - Sidney Santos
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Belém, Pará, PA, Brazil.
| | - Ney P C Dos Santos
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Belém, Pará, PA, Brazil.
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Zhang Z, Zhou B, Gao Q, Wu Y, Zhang K, Pu Y, Song Y, Zhang L, Xi M. A polymorphism at miRNA-122-binding site in the IL-1α 3'UTR is associated with risk of epithelial ovarian cancer. Fam Cancer 2015; 13:595-601. [PMID: 25195148 DOI: 10.1007/s10689-014-9739-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
We aimed to investigate the association between rs3783553 polymorphism and susceptibility to epithelial ovarian cancer in a Chinese population and discussed the risk factors associated with survival time. In a case-control study, 301 patients diagnosed with epithelial ovarian cancer and 240 healthy controls were genotyped for rs3783553 polymorphism. Survival time of ovarian cancer patients was explored by Kaplan-Meier analysis and Cox proportional hazards modeling. The distributions of genotype and allele frequencies were significantly different between cases and controls. The variant homozygote (ins/ins) was associated with a significantly reduced risk of ovarian cancer. The patients with del/ins polymorphism seemed to be diagnosed "earlier" (FIGO stage I-II) and be more likely to achieve optimal cytoreductive surgery. Advanced FIGO stage (stages III-IV) and non-optimal cytoreductive surgery (residual tumor <1 cm) were poor prognostic factors in the univariate analysis. However, optimal cytoreductive surgery was found to be the only independent significant prognostic factor. This study suggests that rs3783553 polymorphism may be involved in the susceptibility to epithelial ovarian cancer. It may also be related with the tumor stage and the ability to achieve optimal tumor surgery, while the latter predicts the clinical outcomes for patients as the only independent prognostic factor.
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Affiliation(s)
- Zhu Zhang
- Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, No. 20, 3rd Section, South Renmin Road, Chengdu, 610041, Sichuan, China,
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Zhang Y, Sturgis EM, Sun Y, Sun C, Wei Q, Huang Z, Li G. A functional variant at miRNA-122 binding site in IL-1α 3' UTR predicts risk and HPV-positive tumours of oropharyngeal cancer. Eur J Cancer 2015; 51:1415-23. [PMID: 25981582 PMCID: PMC4768464 DOI: 10.1016/j.ejca.2015.04.016] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Revised: 04/17/2015] [Accepted: 04/19/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND Genetic polymorphisms in the 3' untranslated regions (3' UTRs) targeted by miRNAs alter the strength of miRNA binding in a manner that affects the behaviour of individual miRNAs. An insertion (Ins)/deletion (Del) polymorphism (rs3783553) in the 3' UTR of IL-1α may disrupt a binding site for miRNA-122. IL-1α plays an important role in inflammation, immunity and defense against infection. Thus, we hypothesised that the rs3783553 polymorphism affects individual susceptibility to human papillomavirus (HPV)-associated oral squamous cell carcinoma (OSCC). METHODS We genotyped the rs3783553 polymorphism; and determined HPV16 L1 serology, tumour HPV16 DNA and serum IL-1α expression. Univariate/multivariable logistic regression models were used to calculate associations. RESULTS We found that HPV16 L1 seropositivity alone was associated with an increased risk of OSCC (Odds ratio (OR), 3.1; 95% confidence interval (CI), 2.1-4.6), and the risk of HPV16-associated OSCC was modified by the rs3783553 polymorphism. Patients with both HPV16 L1 seropositivity and Del/Del genotype for the rs3783553 had the highest risk of OSCC when using patients with HPV16 L1 seronegativity and Ins/Del+Ins/Ins genotypes as a comparison group. Notably, that effect modification was particularly pronounced in several subgroups (e.g. SCCOP, never-smokers and never-drinkers). The patients with Del/Del genotype were approximately 3.0 times more likely to have HPV16-positive squamous cell carcinoma of the oropharynx (SCCOP) tumours compared to those patients with Ins/Del+Ins/Ins genotypes. Additionally, functional relevance of this variant was characterised to explore the genotype-phenotype correlation. CONCLUSION These results suggest that IL-1α 3' UTR rs3783553 polymorphism may be functional and influence susceptibility to HPV16-associated OSCC, particularly for SCCOP. Validation of our findings is warranted.
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Affiliation(s)
- Yang Zhang
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Beijing Institute of Otolaryngology, Beijing 100730, China; Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Erich M Sturgis
- Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yan Sun
- Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Otorhinolaryngology and Head and Neck Surgery, Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Chuanzheng Sun
- Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Head and Neck Surgery, The Tumor Hospital of Yunnan Province, Kunming 650118, China
| | - Qingyi Wei
- Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA
| | - Zhigang Huang
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Beijing Institute of Otolaryngology, Beijing 100730, China; Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
| | - Guojun Li
- Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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Wang JF, Xie Y, Hu L, Li CR, Li HL. Detection of gastric juice microRNAs for screening and diagnosis of gastric cancer. Shijie Huaren Xiaohua Zazhi 2015; 23:2562-2567. [DOI: 10.11569/wcjd.v23.i16.2562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs (miRNAs) are a group of noncoding small RNA molecules (21-25 nucleotides long) which are found in plants and animals. They can regulate the expression of target genes by cleaving and degrading or repressing the translation of target miRNAs. Many studies have confirmed that body fluid miRNAs are closely related to tumor development. This paper introduces the structure, function, characteristics and detection of gastric juice miRNAs, highlighting their role in the screening and diagnosis of gastric cancer.
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Huang J, Ni S, Li D, He Y. An insertion/deletion polymorphism at miRNA-122 binding site in the IL1A is associated with a reduced risk of cervical squamous cell carcinoma. Genet Test Mol Biomarkers 2015; 19:331-4. [PMID: 25955681 DOI: 10.1089/gtmb.2015.0015] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE Previous studies have shown that miRNA plays a key role in cervical carcinogenesis. Interleukin (IL)-1α can promote tumor growth, invasion, migration, and angiogenesis. An insertion/deletion polymorphism (rs3783553) in the IL1A 3' untranslated region may disrupt a binding site for miR-122 and miR-378 and thus change the transcription of IL-1α. The purpose of this study was to evaluate the association between the rs3783553 polymorphism and the risk of cervical squamous cell carcinoma (CSCC). METHODS Polymerase chain reaction was used to genotype the IL1A rs3783553 polymorphism in 235 patients with CSCC and 326 controls. RESULTS We found that the ins/ins genotype had a decreased risk to develop CSCC (odds ratio [OR]=0.48, 95% confidence interval [CI], 0.25-0.95). However, no significant association was observed between the IL1A rs3783553 genotype and clinical features. CONCLUSION These findings indicate that the IL1A rs3783553 polymorphism may be associated with the etiology of CSCC.
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Affiliation(s)
- Juan Huang
- 1 Department of Obstetrics and Gynecology, Chengdu Women's and Children's Central Hospital , Chengdu, People's Republic of China
| | - Shanshan Ni
- 2 Department of Obstetrics and Gynecology, Tianjin Central Hospital of Gynecology Obstetrics , Tianjin, People's Republic of China
| | - Danqing Li
- 3 Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University , Chengdu, People's Republic of China
| | - Yuedong He
- 3 Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University , Chengdu, People's Republic of China
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Nikolić ZZ, Pavićević DLS, Romac SP, Brajušković GN. Genetic variants within endothelial nitric oxide synthase gene and prostate cancer: a meta-analysis. Clin Transl Sci 2014; 8:23-31. [PMID: 25164276 DOI: 10.1111/cts.12203] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Several variants within gene-encoding endothelial isoform of nitric oxide synthase have been reported to confer prostate cancer (PCa) susceptibility and/or progression. Nevertheless, studies referring to this issue have yielded inconsistent results. In order to elucidate the involvement of these variants in prostate carcinogenesis, we have conducted a meta-analysis of previously published case-control and relevant case-only studies. Eleven studies comprising in total 3,806 cases and 4,466 controls were included in the meta-analysis which yielded evidence of association of rs2070744 (ORCC = 1.43, 95% CI 1.04-1.97; p = 0.03) and intron 4a/b variant (ORab+aa = 1.47, 95% CI 1.00-2.14; p = 0.05) with PCa risk under recessive and dominant model, respectively. Furthermore, PCa patients carrying 4a/b a allele were found to have an increased risk of cancer progression to a less differentiated form, characterized by a high Gleason score (OR = 2.29, 95% CI 1.51-3.49; p < 0.01) and to higher TNM stage (OR = 2.55, 95% CI 1.71-3.81; p < 0.01). These results support the involvement of NOS3 variants in molecular pathogenesis of PCa.
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Gao L, Zhu X, Li Z, Li L, Wang T, Hu H, Guo W, Chen P, Zhu J, Zhang L. Association between a functional insertion/deletion polymorphism in IL1A gene and risk of papillary thyroid carcinoma. Tumour Biol 2014; 35:3861-5. [PMID: 24453029 DOI: 10.1007/s13277-013-1512-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Accepted: 12/03/2013] [Indexed: 02/03/2023] Open
Abstract
The aim of this study was to evaluate whether an insertion/deletion polymorphism (rs3783553) locating in the miR-122 target gene IL1A 3' untranslated region was related to the risk of papillary thyroid carcinoma (PTC). Genomic DNA was extracted from peripheral venous blood of 273 patients with PTC and 509 controls. The IL1A rs3783553 polymorphism was genotyped by using a polymerase chain reaction assay. No significant difference of the distribution of the IL1A rs3783553 polymorphism was observed between PTC patients and controls. However, patients carrying the IL1A rs3783553 ins/ins genotype and ins allele had significantly decreased risks for developing T3 and T4 when compared with patients carrying the IL1A rs3783553 del/del genotype and del allele (ins/ins vs. del/del: OR = 0.22, 95% confidence interval (CI), 0.09-0.54; ins vs. del: OR = 0.58, 95% CI, 0.41-0.83, respectively). These results suggest that the rs3783553 polymorphism may be used as a genetic marker to predict the size/extension of PTC.
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Affiliation(s)
- Linbo Gao
- Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China
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