861 Genetic Susceptibility and Family History of Colorectal Cancer. Relevance of Single Nucleotide Polymorphisms in the Development of Preneoplastic Lesions in First-Degree Relatives of Patients With Colorectal Cancer

Abstract Background Gastric cancer is a malignant type of cancer associated with many factors such as environment, behavior, infection, and genetics, which include Single Nucleotide Polymorphism. A few studies revealed polymorphisms of the Mucin 1 gene have a role and significance as a susceptible factor contributing to gastric cancer. The aim of this research is to evaluate the association between Single Nucleotide Polymorphisms of the Mucin 1 gene and Vietnamese gastric cancer patients.Methods 302 gastric cancer patients and 304 controls were interviewed for social-economic characteristics, smoking and drinking status, personal and family history of gastric diseases. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism analysis. The association of Single Nucleotide Polymorphisms with gastric cancer was evaluated using multifactor regression models.Results AA genotype for rs4072037 was found to be highly associated with gastric cancer (OR: 2.07 (95% CI: 1.46-2.90). GG genotype for rs2070803 increased the risk of gastric cancer (OR:1.96 (95% CI: 1.37-2.78). These genotypes in combination with other factors such as old age, male gender, alcoholism and personal history of gastric disease also showed an increased risk of having gastric cancer.Conclusions rs4072037 and rs2070803 of Mucin 1 genes are two genotypic risk factors of gastric cancer. Those in combination with other factors such as gender, family history, smoking and drinking habits significantly increase the risk of gastric cancer.

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Γενετικοί πολυμορφισμοί προφλεγμονωδών και αντιφλεγμονωδών κυτταροκινών και ευπάθεια των νεογνών και βρεφών στην οξεία μέση ωτίτιδα

10.12681/eadd/38960 ◽

2014 ◽

Author(s):

Σταυρούλα Ηλία

Keyword(s):

Family History ◽

Single Nucleotide Polymorphisms ◽

Otitis Media ◽

Inflammatory Cytokine ◽

Early Infancy ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

History Of ◽

Anti Inflammatory ◽

Anti Inflammatory Cytokine

Background: Acute otitis media (AOM) is the most common childhood infection, and despite the lower prevalence in neonates and early infancy, serious complications can occur. Pathogenesis is multi-factorial and little is known on the immature host responses to pathogens during otitis media. Extensive studies on the complex cytokine network and its genetically determined regulation have highlighted the significance as determinants of susceptibility and outcome of AOM.Objective: In the current study we investigated the genetic predisposition of the immune host’s response as related to susceptibility, severity and outcome of AOM in early infancy. For this purpose we have chosen 8 single nucleotide polymorphisms (SNPs) of pro-inflammatory and anti-inflammatory cytokines: IL6 (-174 G→C), IL10 (-1082 G→A, -819 C→T, -592 C→A), TNFα (-308 G→A), INFγ (+874 A→T), TGFβ1 (codon 10 C→T, codon 25 G→C).Methods: Neonates and infants with AOM hospitalized in pediatric units of University Hospital and Venizeleion General Hospital, both in Heraklion, Crete, during 2005-2006 were included and followed-up for three consecutive years. Demographics, history, clinical manifestations, and relapses were recorded. Cytokine single nucleotide polymorphisms were determined by the polymerase chain reaction method. We studied predisposing clinical factors affecting severity and chronicity of the disease, as well as cytokine genotypes as related to susceptibility, clinical course and outcome of AOM. Gender, patient’s atopy, exposure to smoke, siblings, breast feeding, and family history of AOM or atopy were considered as potential covariates in the epidemiological analysis. Results: 96 infants were analyzed, 58 (60.4%) were boys, mean age at enrolment was 2.4 months (range 0.6-7.92), and 52 (54%) were younger than 3 months. At the end of follow-up period, 81 (84.4%) infants presented with recurrent AOM episodes. Gastro-esophageal regurgitation, patient’s atopy and positive family history of AOM were related to increased recurrence rates (p=0.01, p=0.01, and p=0.02 respectively). IL10 (-1082) A and TGFβ1 (codon 10) T minor alleles were related to older age of AOM onset than the wild-type genotypes (p=0.007 and p=0.0039 respectively). As compared to wild genotypes, IL10 (-592 C→A, -819 C→T, -1082 G→A) θαη TGFβ1 (codon 10 C→T) genotypes carrying the alternative gene were related to more AOM episodes (p<0.0001, p<0.0001, p<0.0001, and p=0.002, respectively) and need for tympanostomy tubes (p=0.021, p=0.021, p=0.036, and p=0.049, respectively). The associations remained significant for AOM onset and recurrence after adjusting for confounding factors (multiple regression analysis).Conclusions: Our findings suggest that anti-inflammatory cytokine IL10 and TGFβ1 genotypes influence AOM onset, number of recurrent episodes and tympanostomy tube placement. This evidence expands our understanding toward pathogenesis and outlines the anti-inflammatory cytokine implication in the middle ear inflammation. Immunomodulation of host gene expression and modification of certain polymorphisms could possibly play a significant role in susceptibility and outcome of AOM. Identification of genetically susceptible infants will allow for individualized treatment and prevention strategies.

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

The International Journal of Biological Markers ◽

10.1177/172460080902400206 ◽

2009 ◽

Vol 24 (2) ◽

pp. 99-106 ◽

Cited By ~ 11

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.

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Real-Time Polymerase Chain Reaction as a Method of Express Genetic Typing of Patients with Uterine Leiomyoma: An Example of Three Genetic Polymorphisms

Doctor Ru ◽

10.31550/1727-2378-2021-20-8-7-11 ◽

2021 ◽

Vol 20 (8) ◽

pp. 7-11

Author(s):

M.V. Kuznetsova ◽

◽

K.A. Svirepova ◽

N.S. Sogoyan ◽

A.I. Nikiforova ◽

...

Keyword(s):

Family History ◽

Single Nucleotide Polymorphisms ◽

Real Time ◽

Real Time Pcr ◽

Uterine Leiomyoma ◽

Direct Sequencing ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

History Of ◽

Large Groups

Study Objective: To assess the efficacy of methods for DNA gene typing (direct sequencing and two variants of real-time PCR) for routine analysis of large groups; to compare the prevalence of genotypes of three single nucleotide polymorphisms in groups of women with uterine leiomyoma (with a separate analysis of a group with a family history of the disease) and in controls. Study Design: comparative study. Materials and Methods. Subjects were divided into groups using the case-control principle. DNA gene typing results for two groups of patients were analysed. Also, we analysed prevalence of genotypes in study group (patients with uterine leiomyoma) and in controls (patients without a history of uterine leiomyoma and a family history of the disease). The primary method used for genotyping was direct sequencing with genotype imaging. On the second stage, we tested two different PCR-based genotyping methods. Study Results. Patients with uterine leiomyoma were subject to genotyping using three single nucleotide polymorphisms (rs3020434, rs124577644, rs12637801) in ESR1, FBN2, and KCWMB2 introns. We have identified significant differences in prevalence of genotypes between the study group and controls. Polymorphism prevalence is statistically different between patients with leiomyomas, controls and women with a family history of the disease. It is demonstrated that the use of the two variants of real-time PCR testing instead of direct sequencing speeds up results; these methods are a less expensive and less labour-intensive tool for genotyping of single nucleotide polymorphisms in large groups. Conclusion. Real-time PCR testing can be used for express and efficient analysis of single nucleotide polymorphisms associated with uterine leiomyoma. Both methods (PCR genotyping with the use of oligonucleotide probes and analysis of high-resolution melting profiles) tested in this paper make it possible to get unambiguous results in 97–99% of samples. Keywords: uterine leiomyoma, single nucleotide polymorphisms, family proneness.

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Ability of known susceptibility SNPs to predict colorectal cancer risk for persons with and without a family history

10.1101/267666 ◽

2018 ◽

Author(s):

Mark A. Jenkins ◽

Aung K. Win ◽

James G. Dowty ◽

Robert J. MacInnis ◽

Enes Makalic ◽

...

Keyword(s):

Colorectal Cancer ◽

Family History ◽

Cancer Risk ◽

Colorectal Cancer Risk ◽

Clinical Genetics ◽

Nucleotide Polymorphisms ◽

Men And Women ◽

First Degree Relatives ◽

Risk Reclassification ◽

History Of

ABSTRACTBackgroundA number of single nucleotide polymorphisms (SNPs), which are common inherited genetic variants, have been identified that are associated with risk of colorectal cancer. The aim of this study was to determine the ability of these SNPs to estimate colorectal cancer (CRC) risk for persons with and without a family history of CRC, and the screening implications.MethodsWe estimated the association with CRC of a 45 SNP-based risk using 1,181 cases and 999 controls, and its correlation (r) with CRC risk predicted from detailed family history. We estimated the predicted change in the distribution across predefined risk categories, and implications for recommended age to commence screening, from adding SNP-based risk to family history.ResultsThe inter-quintile risk ratio for colorectal cancer risk of the SNP-based risk was 2.46 (95% CI 1.91 – 3.11). SNP-based and family history-based risks were not correlated (r = 0.02). For persons with no first-degree relatives with CRC, recommended screening would commence 2 years earlier for women (4 years for men) in the highest quintile of SNP-based risk, and 12 years later for women (7 years for men) in the lowest quintile. For persons with two first-degree relatives with CRC, recommended screening would commence 15 years earlier for men and women in the highest quintile, and 8 years earlier for men and women in the lowest quintile.ConclusionsRisk reclassification by 45 SNPs could inform targeted screening for CRC prevention, particularly in clinical genetics settings when mutations in high-risk genes cannot be identified.

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

Biomedicines ◽

10.3390/biomedicines9070808 ◽

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.

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