scholarly journals Risk Model for Colorectal Cancer in Spanish Population Using Environmental and Genetic Factors: Results from the MCC-Spain study

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Gemma Ibáñez-Sanz ◽  
Anna Díez-Villanueva ◽  
M. Henar Alonso ◽  
Francisco Rodríguez-Moranta ◽  
Beatriz Pérez-Gómez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Model ◽  
Vegetable Consumption ◽  
Environmental Data ◽  
Average Risk ◽  
Nucleotide Polymorphisms ◽  
Genetic Score ◽  
Single Nucleotide ◽  
Risk Alleles ◽  
History Of

Abstract Colorectal cancer (CRC) screening of the average risk population is only indicated according to age. We aim to elaborate a model to stratify the risk of CRC by incorporating environmental data and single nucleotide polymorphisms (SNP). The MCC-Spain case-control study included 1336 CRC cases and 2744 controls. Subjects were interviewed on lifestyle factors, family and medical history. Twenty-one CRC susceptibility SNPs were genotyped. The environmental risk model, which included alcohol consumption, obesity, physical activity, red meat and vegetable consumption, and nonsteroidal anti-inflammatory drug use, contributed to CRC with an average per factor OR of 1.36 (95% CI 1.27 to 1.45). Family history of CRC contributed an OR of 2.25 (95% CI 1.87 to 2.72), and each additional SNP contributed an OR of 1.07 (95% CI 1.04 to 1.10). The risk of subjects with more than 25 risk alleles (5th quintile) was 82% higher (OR 1.82, 95% CI 1.11 to 2.98) than subjects with less than 19 alleles (1st quintile). This risk model, with an AUROC curve of 0.63 (95% CI 0.60 to 0.66), could be useful to stratify individuals. Environmental factors had more weight than the genetic score, which should be considered to encourage patients to achieve a healthier lifestyle.

E-Cadherin and Metalloproteinase-1 and -7 Polymorphisms in Colorectal Cancer

2009 ◽  
Vol 24 (2) ◽  
pp. 99-106 ◽  
Author(s):  
Jacqueline Miranda de Lima ◽  
Lessileia Gomes de Souza ◽  
Ismael Dale Cotrim Guerreiro da Silva ◽  
Nora Manoukian Forones
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Metastatic Disease ◽  
Fragment Length Polymorphism ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
History Of ◽  
Polymerase Chain ◽  
Marginal Risk ◽  
E Cadherin

Purpose E-cadherin (CDH1) and metalloproteinase (MMP) polymorphisms could play a crucial role in cancer invasion. Our aim was to investigate the influence of the -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 polymorphisms on the frequency and progression of colorectal cancer (CRC). Experimental design A total of 130 patients with CRC and 130 noncancer controls were studied. The -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Results Patients with the 1G allele and a family history of CRC showed a six times higher risk of developing CRC (OR: 6.45, 95%CI: 2.02–20.6, p=0.001). The A/A CDH1 genotype was associated with a higher risk of metastatic disease (OR: 3.43, 95%CI: 1.27–9.27, p=0.023). A higher marginal risk of metastatic disease was observed for MMP-1 genotypes 1G/1G and 1G/2G (OR: 2.97, 95%CI: 0.93–9.47, p=0.098). Conclusions The -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 single nucleotide polymorphisms did not modify the risk of CRC development. Patients with the 1G/1G or 1G/2G genotype and a family history of CRC presented a higher risk of CRC. The AA CDH1 and 1G/1G and 1G/2G MMP-1 genotypes might be associated with advanced metastatic disease, but are not markers of lymphatic metastasis.

scholarly journals Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 808
Author(s):  
Laura Pérez-Lago ◽  
Teresa Aldámiz-Echevarría ◽  
Rita García-Martínez ◽  
Leire Pérez-Latorre ◽  
Marta Herranz ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Evolutionary Dynamics ◽  
Viral Evolution ◽  
Special Focus ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
New Variant ◽  
History Of ◽  
Evolution Dynamics ◽  
The Uk

A successful Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant, B.1.1.7, has recently been reported in the UK, causing global alarm. Most likely, the new variant emerged in a persistently infected patient, justifying a special focus on these cases. Our aim in this study was to explore certain clinical profiles involving severe immunosuppression that may help explain the prolonged persistence of viable viruses. We present three severely immunosuppressed cases (A, B, and C) with a history of lymphoma and prolonged SARS-CoV-2 shedding (2, 4, and 6 months), two of whom finally died. Whole-genome sequencing of 9 and 10 specimens from Cases A and B revealed extensive within-patient acquisition of diversity, 12 and 28 new single nucleotide polymorphisms, respectively, which suggests ongoing SARS-CoV-2 replication. This diversity was not observed for Case C after analysing 5 sequential nasopharyngeal specimens and one plasma specimen, and was only observed in one bronchoaspirate specimen, although viral viability was still considered based on constant low Ct values throughout the disease and recovery of the virus in cell cultures. The acquired viral diversity in Cases A and B followed different dynamics. For Case A, new single nucleotide polymorphisms were quickly fixed (13–15 days) after emerging as minority variants, while for Case B, higher diversity was observed at a slower emergence: fixation pace (1–2 months). Slower SARS-CoV-2 evolutionary pace was observed for Case A following the administration of hyperimmune plasma. This work adds knowledge on SARS-CoV-2 prolonged shedding in severely immunocompromised patients and demonstrates viral viability, noteworthy acquired intra-patient diversity, and different SARS-CoV-2 evolutionary dynamics in persistent cases.

scholarly journals NLRP1 influences the systemic sclerosis phenotype: a new clue for the contribution of innate immunity in systemic sclerosis-related fibrosing alveolitis pathogenesis

2010 ◽  
Vol 70 (4) ◽  
pp. 668-674 ◽  
Author(s):  
P Dieudé ◽  
M Guedj ◽  
J Wipff ◽  
B Ruiz ◽  
G Riemekasten ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Systemic Sclerosis ◽  
Potential Role ◽  
Additive Model ◽  
Nucleotide Polymorphisms ◽  
Fibrosing Alveolitis ◽  
Single Nucleotide ◽  
Risk Alleles ◽  
Caucasian Origin

BackgroundRecent evidence has highlighted a potential role of interleukin 1β (IL-1β) in systemic sclerosis (SSc). NLRP1 provides a scaffold for the assembly of the inflammasome that promotes the processing and maturation of pro-IL-1β. In addition, NLRP1 variants were found to confer susceptibility to autoimmune disorders.ObjectiveTo study a possible association of the NLRP1 rs6502867, rs2670660 and rs8182352, rs12150220 and rs4790797 with SSc in the European Caucasian population.MethodsNLRP1 single nucleotide polymorphisms were genotyped in 3227 individuals comprising a discovery set (870 SSc patients and 962 controls) and a replication set including individuals from Germany (532 SSc patients and 324 controls) and Italy (527 SSc patients and 301 controls), all individuals being of European Caucasian origin.ResultsConditional analyses revealed a significant association for the NLRP1 rs8182352 variant with both anti-topoisomerase-positive and SSc-related fibrosing alveolitis (FA) subsets under an additive model: p=0.0042, OR 1.23 (95% CI 1.07 to 1.41) and p=0.0065 OR 1.19 (95% CI 1.05 to 1.36), respectively. Logistic regression analysis showed an additive effect of IRF5 rs2004640, STAT4 rs7574865 and NLRP1 rs8182352 risk alleles on SSc-related FA.ConclusionsOur results establish NLRP1 as a new genetic susceptibility factor for SSc-related pulmonary fibrosis and anti-topoisomerase-positive SSc phenotypes. This provides new insights into the pathogenesis of SSc, underlining the potential role of innate immunity in particular in the FA-positive SSc subphenotype, which represents a severe subset of the disease.

scholarly journals Single nucleotide polymorphisms in Wnt signaling and cell death pathway genes and susceptibility to colorectal cancer

2010 ◽  
Vol 31 (8) ◽  
pp. 1381-1386 ◽  
Author(s):  
B. Frank ◽  
M. Hoffmeister ◽  
N. Klopp ◽  
T. Illig ◽  
J. Chang-Claude ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Single Nucleotide Polymorphisms ◽  
Wnt Signaling ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Cell Death Pathway

scholarly journals Single Nucleotide Polymorphism in SMAD7 and CHI3L1 and Colorectal Cancer Risk

2018 ◽  
Vol 2018 ◽  
pp. 1-23 ◽  
Author(s):  
Amal Ahmed Abd El-Fattah ◽  
Nermin Abdel Hamid Sadik ◽  
Olfat Gamil Shaker ◽  
Amal Mohamed Kamal
Keyword(s):  
Colorectal Cancer ◽  
Genetic Variation ◽  
Sequence Variation ◽  
Regulatory Protein ◽  
Nucleotide Polymorphisms ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
The Third ◽  
Common Cancer ◽  
Cancer Initiation

Colorectal cancer (CRC) is one of the leading cancers throughout the world. It represents the third most common cancer and the fourth in mortality. Most of CRC are sporadic, arise with no known high-penetrant genetic variation and with no previous family history. The etiology of sporadic CRC is considered to be multifactorial and arises from the interaction of genetic variants of low-penetrant genes and environmental risk factors. The most common well-studied genetic variation is single nucleotide polymorphisms (SNPs). SNP arises as a point mutation. If the frequency of the sequence variation reaches 1% or more in the population, it is referred to as polymorphism, but if it is lower than 1%, the allele is typically considered as a mutation. Lots of SNPs have been associated with CRC development and progression, for example, genes of TGF-β1 and CHI3L1 pathways. TGF-β1 is a pleiotropic cytokine with a dual role in cancer development and progression. TGF-β1 mediates its actions through canonical and noncanonical pathways. The most important negative regulatory protein for TGF-β1 activity is termed SMAD7. The production of TGF-βcan be controlled by another protein called YKL-40. YKL-40 is a glycoprotein with an important role in cancer initiation and metastasis. YKL-40 is encoded by the CHI3L1 gene. The aim of the present review is to give a brief introduction of CRC, SNP, and examples of some SNPs that have been documented to be associated with CRC. We also discuss two important signaling pathways TGF-β1 and CHI3L1 that influence the incidence and progression of CRC.

scholarly journals Genome-wide profiling in colorectal cancer identifies PHF19 and TBC1D16 as oncogenic super enhancers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qing-Lan Li ◽  
Xiang Lin ◽  
Ya-Li Yu ◽  
Lin Chen ◽  
Qi-Xin Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Cancer Patient ◽  
Nucleotide Polymorphisms ◽  
Rna Seq ◽  
Motif Analysis ◽  
Single Nucleotide ◽  
Super Enhancer ◽  
Genome Wide ◽  
Functional Factors ◽  
Cancer Tissues

AbstractColorectal cancer is one of the most common cancers in the world. Although genomic mutations and single nucleotide polymorphisms have been extensively studied, the epigenomic status in colorectal cancer patient tissues remains elusive. Here, together with genomic and transcriptomic analysis, we use ChIP-Seq to profile active enhancers at the genome wide level in colorectal cancer paired patient tissues (tumor and adjacent tissues from the same patients). In total, we sequence 73 pairs of colorectal cancer tissues and generate 147 H3K27ac ChIP-Seq, 144 RNA-Seq, 147 whole genome sequencing and 86 H3K4me3 ChIP-Seq samples. Our analysis identifies 5590 gain and 1100 lost variant enhancer loci in colorectal cancer, and 334 gain and 121 lost variant super enhancer loci. Multiple key transcription factors in colorectal cancer are predicted with motif analysis and core regulatory circuitry analysis. Further experiments verify the function of the super enhancers governing PHF19 and TBC1D16 in regulating colorectal cancer tumorigenesis, and KLF3 is identified as an oncogenic transcription factor in colorectal cancer. Taken together, our work provides an important epigenomic resource and functional factors for epigenetic studies in colorectal cancer.

Presence of CAT genetic markers as an indicator of accelerated rate of liver fibrosis progression in patients with chronic hepatitis

2021 ◽  
Vol 1 (5) ◽  
pp. 39-43
Author(s):  
I. A. Bulatova ◽  
T. P. Shevlyukova ◽  
A. P. Shchekotova ◽  
A. V. Krivtsov
Keyword(s):  
Chronic Hepatitis ◽  
Liver Fibrosis ◽  
Genetic Markers ◽  
Rapid Progression ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Risk Alleles ◽  
Slow Progression ◽  
Polymerase Chain ◽  
Number Of Individuals

Goal. To evaluate the genetic profi le of patients with chronic hepatitis C (CHC) by the CAT gene polymorphism in the region-262G/A (rs1001179), GPX4 in the region-718C/T (rs713041), IL28B in the region C/T (rs12979860) and VEGFA in the region- 634G/C (rs2010963) to analyze the association of the rate of progression of liver fi brosis with polymorphic genetic markers.Materials and methods. We examined 36 patients with CHC with a rapidly progressive rate of fi brosis (up to 10 years) and 56 patients with a slowly progressive course of the disease (more than 10 years). The study of single- nucleotide polymorphisms of genes was carried out by the method of polymerase chain reaction.Results. In the group with rapid progression of liver fi brosis, individuals with multiple risk alleles for the studied polymorphisms were more common, which confi rms the association of the risk of liver fi brosis progression with the genetic markers CAT in the region-262G/A (rs1001179) and GPX4 in the region-718C/T (rs713041) with their combined carrier. Among patients with rapid progression of fi brosis, a greater number of individuals had simultaneously 4–6 risk alleles in 27.5%, while patients with slow progression of the process only in 11% of cases.Conclusion. This set of genetic markers can be used as genetic testing of patients with liver fibrosis to determine the prognosis of the disease.

Deletion and Single Nucleotide Polymorphisms in Common Glutathione-S Transferases Contribute to Colorectal Cancer Development

2019 ◽  
Vol 25 (4) ◽  
pp. 1579-1587 ◽  
Author(s):  
Milica Lj. Stojkovic Lalosevic ◽  
Vesna M. Coric ◽  
Tatjana D. Pekmezovic ◽  
Tatjana P. Simic ◽  
Marija S. Pljesa Ercegovac ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Cancer Development ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Glutathione S Transferases
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