scholarly journals Genetic Polymorphisms of FOXO3a Gene in Colorectal Cancer among North Indian Population

2021 ◽  
Author(s):  
Laraib Uroog ◽  
Zafar Iqbal Bhat ◽  
Bushra Zeya ◽  
Khalid Imtiyaz ◽  
Rauf AHMAD Wani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Polymerase Chain Reaction ◽  
Cancer Patients ◽  
Statistical Significance ◽  
Incidence Rates ◽  
Risk Haplotype ◽  
Chain Reaction ◽  
Increased Risk ◽  
Polymerase Chain ◽  
Colorectal Cancer Patients

Abstract Background Colorectal cancer (CRC) heritability is determined by the composite relations between inherited variants and environmental factors. In developing countries like India CRC incidence rates have been increasing specially. In the present study, we focused on the distribution of FOXO3a gene polymorphisms in North Indian colorectal cancer patients. Methods A case–control study was conducted on 900 samples including 450 colorectal cancer patients and 450 age matched controls. We genotyped the SNPs rs2253310 and rs4946936 via Polymerase Chain Reaction-Restriction fragment length polymorphism (RFLP) analysis and Polymerase Chain Reaction- single stranded conformation polymorphism (SSCP) procedure followed by sequence detection. Results A significantly increased risk of CRC was observed with rs4946936 genotype (P= 0.0393; OR= 1.405 CI=1.051-1.879). GT haplotype although not reaching statistical significance appeared to be at higher “risk” haplotype (OR- 1.164, 95%CI= 0.967~1.401), while as other haplotypes CC (OR- 0.893, 95% CI=0.665~1.200]), CT (OR- 0.806, 95%CI= 0.616~1.055) and GC (OR- 0.994, 95%CI= 0.809~1.221) were found to be “protective” for developing colorectal cancer. Conclusion This study lends support for an increased risk of CRC associated with the rs4946936 polymorphism. Nevertheless, statistically significant association between rs2253310 genotypes and CRC risk was not observed.

scholarly journals The association of a single-nucleotide variant in the microRNA-146a with advanced colorectal cancer prognosis

Tumor Biology ◽  
2020 ◽  
Vol 42 (5) ◽  
pp. 101042832092385
Author(s):  
Jéssica Silva dos Santos ◽  
Gabriella Lucatto Zunta ◽  
Amanda Binatto Negrini ◽  
Marina Silva Guinda Ribeiro ◽  
Carlos Augusto Real Martinez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Polymerase Chain Reaction ◽  
Cancer Patients ◽  
Untranslated Region ◽  
Single Nucleotide Variant ◽  
Chain Reaction ◽  
Single Nucleotide ◽  
Polymerase Chain ◽  
Colorectal Cancer Patients ◽  
Ht 29

The aim of this study was to evaluate the association of single-nucleotide variant n.60G>C (rs2910164) of microRNA (miR)-146a, related to suppressing of BRCA1/2 DNA repair protein, with the risk and survival of colorectal cancer patients, as well as miR-146a and BRCA1/2 levels and miR binding efficiency. The genotypes were identified in 125 colorectal cancer patients and 276 controls using TaqMan polymerase chain reaction assay. The miR-146a and BRCA1/2 levels were assessed by quantitative–polymerase chain reaction protocols. Primary precursor of miR-146a containing G (wild-type) and C (variant) allele were cloned into pcDNA.3.3 vector and co-transfected in HT-29 colorectal cancer cell line. Luciferase reporter assay was performed to assess miR-146a binding to BRCA2 3′-untranslated region in HT-29. The differences between groups were calculated using chi-square or Fisher’s exact test, logistic regression, and Mann–Whitney test. The prognostic impact of single-nucleotide variant genotypes on overall survival was evaluated by Kaplan–Meier estimate and Cox regression. The GC or CC genotypes prevalence was similar in patients and controls (50.4% vs 50.7%, p = 0.74). However, patients with tumors in advanced stage with miR-146a GG genotype had 2.41 more chance of dying than GC or CC genotypes. In addition, tumor tissues of patients with GG genotype presented higher miR-146a ( p = 0.02) and lower BRCA1 ( p = 0.01) and BRCA2 ( p < 0.0001) levels when compared to those with GC or CC genotypes. In fact, pcDNA.3.3-miR-146a-G presented increased binding capacity to the 3′-untranslated region of BRCA2 ( p = 0.001) compared to pcDNA.3.3-miR-146a-C. In addition, the G allele altered the binding affinity between miR-146a and its BRCA2 3′-untranslated region target ( p < 0.001), thus enhancing suppression of BRCA2 expression. Our results suggest that single-nucleotide variant rs2910164 does not influence the colorectal cancer risk in Brazilian patients; however, the GG genotype could act as a factor of worse prognosis in patients with advanced disease due to suppression of BRCA1/2 modulated by miR-146a.

Baseline lymphopenia as a prognostic marker for colorectal carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14107-e14107
Author(s):  
Dilek Erdem ◽  
Idris Yucel ◽  
Bahiddin Yilmaz ◽  
Guzin Demirag ◽  
Yasemin Kemal ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Lymphocyte Count ◽  
Statistical Significance ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Hematological Toxicity ◽  
Free Survival ◽  
Increased Risk ◽  
Colorectal Cancer Patients

e14107 Background: Baseline lymphopenia has been proved to be a marker for poor prognosis, chemotherapy-induced toxicity and increased risk of febrile neutropenia, trombocytopenia and anemia in advanced solid neoplasms. This study aims to evaluate the effect of pretreatment lymphopenia on prognosis and hematological toxicity in colorectal cancer patients who received first line systemic chemotherapy. Methods: Lymphocyte count was evaluated in 386 pretreated colorectal cancer patients who do not have a seconder malignancy, HIV infection, bone involvement and primary G-CSF prophylaxis. Overall survival, progression free survival and disease free survival were calculated from date of diagnosis to date of relapse, progression and death. Kaplan-Meier, chi-square and Student-t test were used. Results: Mean follow-up was 30 months (range 1-180 months). Mean age was 57.4±12.5 years. Of all patients, 160 (41 %) were women. Rectum ( 26.2 %) and transvers colon (4.7 %) were the most and the least common anatomic locations, respectively. Mean lymphocyte count before treatment was 1964/µl (170-7000/µl). There were no relationship between lymphopenia and age, sex, performans status, presence of initial metastasis, adjuvant or palliative chemotherapy and hematological toxicity (p>0.05). Grade 3-4 hematological toxicity was found in 40 patients and was significantly higher in patients receiving bi- or tri-chemotherapy regimen (p:0.017). Among 208 patients with relapse or progression, 40 patients had lymphopenia (19.2 %). 1, 3 and 5-year OS were significantly lower in lymphopenic patients (p:0.033). DFS was longer in non-lymphopenic patients but this data didn’t have statistical significance (p>0.05). Conclusions: This study support that lymphocyte number prior to chemotherapy may be a simple but useful prognostic and predictive marker in untreated colorectal cancer patients. Patients with lower pretreatment lymphopenia have lower OS when compared to others (p<0.05). This study has the highest colorectal cancer population in the literature.

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