scholarly journals Association analysis of miRNA-related genetic polymorphisms in miR-143/145 and KRAS  with colorectal cancer susceptibility and survival

2021 ◽  
Author(s):  
Danyang Wang ◽  
Qingmin Liu ◽  
Yanjun Ren ◽  
Yan Zhang ◽  
Xin Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Genetic Polymorphisms ◽  
Target Gene ◽  
Cancer Susceptibility ◽  
Gene Interaction ◽  
Tertiary Hospital ◽  
Cancer Tissue ◽  
Nucleotide Polymorphisms ◽  
Aberrant Expression ◽  
Genomic Regions

Background There is accumulating evidence of aberrant expression of miR-143 and miR-145 and their target gene KRAS in colorectal cancer (CRC). We hypothesize that single nucleotide polymorphisms (SNPs) within or near mRNA-miRNA binding sites may affect miRNA/target gene interaction, resulting in differential mRNA/protein expression and promoting the development and progression of CRC. Methods We conducted a case-control study of 507 patients with CRC recruited from a tertiary hospital and 497 population-based controls to assess the association of genetic polymorphisms in miR-143/145 and the KRAS 3′untranslated region (3′UTR) with susceptibility to CRC and patients’ survival. In addition, genetic variations of genomic regions located from 500 bp upstream to 500 bp downstream of the miR-143/miR-145 gene and the 3′UTR of KRAS were selected for analysis using the Haploview and HaploReg software. Results Using publicly available expression profiling data, we found that miR-143/145 and KRAS expression were all reduced in rectal cancer tissue compared to adjacent non-neoplastic large intestinal mucosa. The rs74693964 C/T variant located 65 bp downstream of miR-145 genomic regions was observed to be associated with susceptibility to CRC (adjusted odds ratio 2.414, 95% CI: 1.385–4.206). Cumulative effects of miR-143 and miR-145 on CRC risk were observed (Ptrend=0.03). Patients having CRC carrying variant genotype TT of KRAS rs712 had poorer survival (log-rank P=0.044, adjusted hazard ratio 4.328, 95% CI: 1.236–15.147). Conclusions Our results indicate that miRNA-related polymorphisms in miR-143/145 and KRAS are likely to be deleterious and represent potential biomarkers for susceptibility to CRC and  patients’ survival.

scholarly journals Association analysis of miRNA-related genetic polymorphisms in miR-143/145 and KRAS with colorectal cancer susceptibility and survival

2019 ◽  
Author(s):  
Danyang Wang ◽  
Qingmin Liu ◽  
Yanjun Ren ◽  
Yan Zhang ◽  
Xin Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Genetic Polymorphisms ◽  
Target Gene ◽  
Cancer Registration ◽  
Cancer Tissue ◽  
Aberrant Expression ◽  
Registration System ◽  
Increased Risk ◽  
Genomic Regions

Abstract Background MicroRNAs have important roles in tumorigenesis. There is accumulating evidence of aberrant expression of miR-143 and miR-145 and their target gene KRAS has been described in colorectal cancer (CRC). We hypothesize that single nucleotide polymorphisms (SNPs) within or near mRNA-miRNA binding sites may affect miRNA/target gene interaction, resulting in differential mRNA/protein expression and promoting the development and progression of CRC.Methods We conducted a case-control study of 507 CRC cases recruited from a tertiary hospital and 497 population-based controls to assess the association of genetic polymorphisms in miR-143/145 and the KRAS 3′ untranslated region (3′ UTR) with CRC susceptibility and survival. Deaths and causes of death among the CRC cases were identified using the Hangzhou Cancer Registration System and Death Surveillance System. Genetic variations of genomic regions located from 500 bp upstream to 500 bp downstream of the miR-143/miR-145 gene and the 3′ UTR of KRAS were selected using the Haploview and HaploReg software. Results Using publicly available expression profiling data, we found that miR-143/145 and KRAS expression were all reduced in rectal cancer tissue compared with adjacent normal mucosa. The Rs74693964 C/T variant located 65 bp downstream of miR-145 genomic regions was observed to be associated with CRC susceptibility (adjusted odds ratio 2.414, 95% CI: 1.385–4.206). Among non-smokers, the miR-143 rs41291957 GA genotype and miR-145 rs74693964 CT genotype were borderline significantly associated with an increased risk of rectal cancer. However, there was no interaction effect between selected SNPs and smoking status. Cumulative effects of miR-143 and miR-145 on CRC risk were observed (Ptrend=0.03). CRC cases carrying variant genotype TT of KRAS rs712 had poorer survival (log-rank P=0.044, adjusted hazard ratio 4.328, 95% CI: 1.236–15.147). Conclusions Our results indicate that miRNA-related polymorphisms in miR-143/145 and KRAS are likely to be deleterious and represent potential biomarkers for CRC susceptibility and survival.

scholarly journals Genetic polymorphisms in XRCC1 genes and colorectal cancer susceptibility

2015 ◽  
Vol 13 (1) ◽  
Author(s):  
Yi Huang ◽  
Xiaohua Li ◽  
Jing He ◽  
Lin Chen ◽  
Huaxing Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Genetic Polymorphisms ◽  
Cancer Susceptibility

scholarly journals Genetic Polymorphisms in the Vitamin D Pathway and Non-small Cell Lung Cancer Survival

2019 ◽  
Vol 26 (3) ◽  
pp. 1709-1715 ◽  
Author(s):  
Jinyu Kong ◽  
Xiaojie Chen ◽  
Jian Wang ◽  
Jingxin Li ◽  
Fangxiu Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Vitamin D ◽  
Small Cell Lung Cancer ◽  
Genetic Polymorphisms ◽  
Cell Lung Cancer ◽  
Cancer Survival ◽  
Cancer Susceptibility ◽  
Small Cell ◽  
Nucleotide Polymorphisms ◽  
Small Cell Lung

Abstract Various genetic polymorphisms have been linked to lung cancer susceptibility and survival outcomes. Vitamin D (VD) regulates cell proliferation and differentiation, inhibits tumor growth and induces apoptosis. Observations from several previous studies including our own suggest that genetic polymorphisms in the VD pathway may be associated with lung cancer risk. The aim of this study is to assess if genetic polymorphisms in the VD pathway are associated with the prognosis of non-small cell lung cancer (NSCLC). Nine single nucleotide polymorphisms (SNPs) in five genes in the VD pathway were genotyped with the TaqMan assays in 542 patients with primary NSCLC, and the relationships between these SNPs and overall survival were evaluated. We found that SNP rs10741657 in the CYP2R1 gene was associated with the prognosis of NSCLC, especially in elderly patients and not being treated with chemotherapy. Some of the VD pathway-related genetic polymorphisms may influence the prognosis of NSCLC. More research is needed to further confirm the finding and test if VD supplements can be used for NSCLC treatment.

scholarly journals Single Nucleotide Polymorphism in hsa-mir-196a-2 and Breast Cancer Risk: A Case Control Study

2011 ◽  
Vol 14 (5) ◽  
pp. 417-421 ◽  
Author(s):  
Dominik J. Jedlinski ◽  
Plamena N. Gabrovska ◽  
Stephen R. Weinstein ◽  
Robert A. Smith ◽  
Lyn R. Griffiths
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Case Control ◽  
Cancer Tissue ◽  
Transcriptional Level ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

microRNAs are small, non-coding RNAs that influence gene expression on a post-transcriptional level. They participate in diverse biological pathways and may act as either tumor suppressor genes or oncogenes. As they may have an effect on thousands of target mRNAs, single-nucleotide polymorphisms in microRNA genes might have major functional consequences, because the microRNA's properties and/or maturation may change. miR-196a has been reported to be aberrantly expressed in breast cancer tissue. Additionally, the SNP rs11614913 in hsa-mir-196a-2 has been found to be associated with breast cancer risk in some studies although not in others. This study evaluated the association between rs11614913 and breast cancer risk in a Caucasian case-control cohort in Queensland, Australia. Results do not support an association of the tested hsa-mir-196a-2 polymorphism with breast cancer susceptibility in this cohort. As there is a discrepancy between our results and previous findings, it is important to assess the role of rs11614913 in breast cancer by further larger studies investigating different ethnic groups.

scholarly journals lncRNA-PCAT1 rs2632159 polymorphism could be a biomarker for colorectal cancer susceptibility

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Ming-li Yang ◽  
Zhe Huang ◽  
Li-na Wu ◽  
Rong Wu ◽  
Han-xi Ding ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Bioinformatic Analysis ◽  
Recessive Model ◽  
Eqtl Analysis ◽  
Nucleotide Polymorphisms ◽  
Colon Cancer Risk

AbstractBackground: Single-nucleotide polymorphisms (SNPs) in lncRNAs could be biomarkers for susceptibility to colorectal cancer (CRC), but the association of PCAT1 polymorphisms and CRC susceptibility is yet to be studied. Methods: Five tagSNPs covering the PCAT1 gene were detected through Kompetitive Allele-Specific PCR among 436 CRC patients and 510 controls. An expression quantitative trait locus (eQTL) bioinformatic analysis was then performed. Results: In the present study, PCAT1 rs2632159 polymorphism increased CRC risk by 1.37-fold and 2.19-fold in the dominant and recessive models, respectively (P=0.040 and 0.041). When the CRC cases were divided into colon cancer and rectal cancer, we found that this polymorphism affected colon cancer risk under the dominant model (P=0.022, OR = 1.51) and affected rectal cancer susceptibility under the recessive model (P=0.009, OR = 3.03). A more pronounced effect was observed in the male subgroup in that PCAT1 rs2632159 SNP increased rectal cancer risk by 3.97-fold (P=0.017). When PCAT1 rs2632159 was present, epistatic effects were observed with rs1902432 and rs785005 (P=0.011 and 0.008, respectively). eQTL analysis showed that rs2632159 could influence binding with the transcription factors EBF, LUN-1, and TCF12. Conclusion:PCAT1 rs2632159 SNP could be a biomarker for CRC risk. And the rs1902432 SNP might only have potential to be a biomarker for colon cancer risk.

scholarly journals In-silico analysis of MHC genes in hereditary colorectal cancer shows identical by state SNP sharing affecting HLA-DQB1 binding groove

2016 ◽  
Author(s):  
Mahmoud Koko ◽  
Suleiman Hussein Suleiman ◽  
Mohammed Omar Elsiddieg Abdallah ◽  
Muhallab Saad ◽  
Muntaser Ibrahim
Keyword(s):  
Colorectal Cancer ◽  
In Silico ◽  
Cancer Susceptibility ◽  
Human Leukocyte ◽  
Hereditary Colorectal Cancer ◽  
The Cancer Genome Atlas ◽  
Exome Capture ◽  
Nucleotide Polymorphisms ◽  
Mhc Ii ◽  
Binding Groove

Background: The role of Human Leukocyte Antigen (HLA) alleles in colorectal cancer susceptibility, development and progression is the focus of ongoing scrutiny. MHC polymorphisms in a Sudanese family with hereditary colorectal cancer were studied using an in silico approach and the results were verified using The Cancer Genome Atlas (TCGA). In this family study, we tested for sharing of nucleotide polymorphisms identified by whole exome capture in major histocompatibility complex region and carried out in-silico prediction of their effects in tumor and control samples. SNPs were analyzed to highlight identical by state sharing, to identify runs of homozygosity, as well as to predict structural and functional effects using homology modeling, damaging effect predictions, and regulatory changes prediction. Results: MHC II area showed significantly high degree of homozygosity in tumor samples. Non-synonymous SNPs shared identical by state (IBS) between tumor samples were predicted to affect HLA-DQB1 binding groove. A similar haplotype of these SNPs was identified in a TCGA colonic adenocarcinoma tumor sample. No significant regulatory effects (in the form of transcription factor or miRNA binding site variants) were predicted. Conclusions: The results demonstrate IBS SNP sharing of markers affecting HLA-DQB1 binding specificity and probable loss of heterozygosity in MHC II region in colorectal cancer.

scholarly journals Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mengting Sun ◽  
Tingting Wang ◽  
Peng Huang ◽  
Jingyi Diao ◽  
Senmao Zhang ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Genetic Polymorphisms ◽  
Congenital Heart ◽  
Septal Defect ◽  
Ductus Arteriosus ◽  
Gene Interaction ◽  
Mthfr Gene ◽  
Nucleotide Polymorphisms ◽  
Locus Model

Abstract Background Although many studies showed that the risk of congenital heart disease (CHD) was closely related to genetic factors, the exact pathogenesis is still unknown. Our study aimed to comprehensively assess the association of single nucleotide polymorphisms (SNPs) of maternal MTHFR gene with risk of CHD and its three subtypes in offspring. Methods A case–control study involving 569 mothers of CHD cases and 652 health controls was conducted. Thirteen SNPs were detected and analyzed. Results Our study showed that genetic polymorphisms of maternal MTHFR gene at rs4846052 and rs1801131 were significantly associated with risk of CHD in the homozygote comparisons (TT vs. CC at rs4846052: OR = 7.62 [95%CI 2.95–19.65]; GG vs. TT at rs1801131: OR = 5.18 [95%CI 2.77–9.71]). And six haplotypes of G–C (involving rs4846048 and rs2274976), A–C (involving rs1801133 and rs4846052), G–T (involving rs1801133 and rs4846052), G–T–G (involving rs2066470, rs3737964 and rs535107), A–C–G (involving rs2066470, rs3737964 and rs535107) and G–C–G (involving rs2066470, rs3737964 and rs535107) were identified to be significantly associated with risk of CHD. Additionally, we observed that a two-locus model involving rs2066470 and rs1801131 as well as a three-locus model involving rs227497, rs1801133 and rs1801131 were significantly associated with risk of CHD in the gene–gene interaction analyses. For three subtypes including atrial septal defect, ventricular septal defect and patent ductus arteriosus, similar results were observed. Conclusions Our study indicated genetic polymorphisms of maternal MTHFR gene were significantly associated with risk of fetal CHD in the Chinese population. Additionally, there were significantly interactions among different SNPs on risk of CHD. However, how these SNPs affect the development of fetal heart remains unknown, and more studies in different ethnic populations and with a larger sample are required to confirm these findings.

scholarly journals Polymorphisms of a novel long non-coding RNA RP11-108K3.2 with colorectal cancer susceptibility and their effects on its expression

2019 ◽  
Vol 35 (1) ◽  
pp. 3-9
Author(s):  
Danjie Jiang ◽  
Mingjuan Jin ◽  
Ding Ye ◽  
Yingjun Li ◽  
Fangyuan Jing ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Susceptibility ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Chinese Populations ◽  
Lncrna Transcript ◽  
Validated Questionnaire ◽  
Non Coding Rna ◽  
Validation Set ◽  
Long Non Coding Rna

Background: RP11-108K3.2 was recently identified as a novel long non-coding RNA (lncRNA) transcript, and several single nucleotide polymorphisms (SNPs) have been identified in its coding region. This study aimed to explore the associations of tagSNPs in RP11-108K3.2 with the risk of colorectal cancer and their effects on its expression. Methods: A total of 821 colorectal cancer cases and 857 healthy controls were enrolled into this two-stage case-control study. Demographic characteristics and lifestyle information were collected by a validated questionnaire. Six tagSNPs were genotyped by using Sequenom MassARRAY platform. A total of 71 additional colorectal cancer cases were recruited, of which the genotypes of potential polymorphisms and the RP11-108K3.2 expression levels were determined. Results: In the discovery set, only the rs2470151 C/T polymorphism was found to have a promising association with the risk of colorectal cancer, and this polymorphism was further replicated in the validation set with a significantly decreased risk of colorectal cancer (adjusted odds ratio 0.73; 95% confidence interval 0.55, 0.97). Combined discovery set and validation set together, this negative association was found both in the heterozygote codominant model and the dominant model. Furthermore, colorectal cancer patients carrying rs2470151 CT/TT genotypes had a marginally lower RNA expression of RP11-108K3.2 than those carrying the CC genotype. Stratified analyses showed the association between rs2470151 and the risk of colorectal cancer were influenced by family history of cancer, smoking, alcohol consumption, and tea drinking. Conclusions: These findings suggest that RP11-108K3.2 rs2470151 had a significant association with the risk of colorectal cancer; this may help to predict the susceptibility of colorectal cancer in Chinese populations.

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