scholarly journals Characterising cis-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues

Gut ◽  
2017 ◽  
Vol 67 (3) ◽  
pp. 521-533 ◽  
Author(s):  
Mingfeng Zhang ◽  
Soren Lykke-Andersen ◽  
Bin Zhu ◽  
Wenming Xiao ◽  
Jason W Hoskins ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Cancer Risk ◽  
Regulatory Element ◽  
Pancreatic Tissue ◽  
The Cancer Genome Atlas ◽  
Eqtl Analysis ◽  
Data Set ◽  
Tissue Samples ◽  
Pancreatic Cancer Risk

ObjectiveTo elucidate the genetic architecture of gene expression in pancreatic tissues.DesignWe performed expression quantitative trait locus (eQTL) analysis in histologically normal pancreatic tissue samples (n=95) using RNA sequencing and the corresponding 1000 genomes imputed germline genotypes. Data from pancreatic tumour-derived tissue samples (n=115) from The Cancer Genome Atlas were included for comparison.ResultsWe identified 38 615 cis-eQTLs (in 484 genes) in histologically normal tissues and 39 713 cis-eQTL (in 237 genes) in tumour-derived tissues (false discovery rate <0.1), with the strongest effects seen near transcriptional start sites. Approximately 23% and 42% of genes with significant cis-eQTLs appeared to be specific for tumour-derived and normal-derived tissues, respectively. Significant enrichment of cis-eQTL variants was noted in non-coding regulatory regions, in particular for pancreatic tissues (1.53-fold to 3.12-fold, p≤0.0001), indicating tissue-specific functional relevance. A common pancreatic cancer risk locus on 9q34.2 (rs687289) was associated with ABO expression in histologically normal (p=5.8×10−8) and tumour-derived (p=8.3×10−5) tissues. The high linkage disequilibrium between this variant and the O blood group generating deletion variant in ABO (exon 6) suggested that nonsense-mediated decay (NMD) of the ‘O’ mRNA might explain this finding. However, knockdown of crucial NMD regulators did not influence decay of the ABO ‘O’ mRNA, indicating that a gene regulatory element influenced by pancreatic cancer risk alleles may underlie the eQTL.ConclusionsWe have identified cis-eQTLs representing potential functional regulatory variants in the pancreas and generated a rich data set for further studies on gene expression and its regulation in pancreatic tissues.

scholarly journals Deep learning-based gene selection in comprehensive gene analysis in pancreatic cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yasukuni Mori ◽  
Hajime Yokota ◽  
Isamu Hoshino ◽  
Yosuke Iwatate ◽  
Kohei Wakamatsu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Deep Learning ◽  
Gene Selection ◽  
Pancreatic Tissue ◽  
Expression Data ◽  
Tissue Samples ◽  
Normal Pancreatic Tissue ◽  
Model Training ◽  
Selection Of

AbstractThe selection of genes that are important for obtaining gene expression data is challenging. Here, we developed a deep learning-based feature selection method suitable for gene selection. Our novel deep learning model includes an additional feature-selection layer. After model training, the units in this layer with high weights correspond to the genes that worked effectively in the processing of the networks. Cancer tissue samples and adjacent normal pancreatic tissue samples were collected from 13 patients with pancreatic ductal adenocarcinoma during surgery and subsequently frozen. After processing, gene expression data were extracted from the specimens using RNA sequencing. Task 1 for the model training was to discriminate between cancerous and normal pancreatic tissue in six patients. Task 2 was to discriminate between patients with pancreatic cancer (n = 13) who survived for more than one year after surgery. The most frequently selected genes were ACACB, ADAMTS6, NCAM1, and CADPS in Task 1, and CD1D, PLA2G16, DACH1, and SOWAHA in Task 2. According to The Cancer Genome Atlas dataset, these genes are all prognostic factors for pancreatic cancer. Thus, the feasibility of using our deep learning-based method for the selection of genes associated with pancreatic cancer development and prognosis was confirmed.

Genetic variants in taste-related genes and risk of pancreatic cancer

Mutagenesis ◽  
2019 ◽  
Vol 34 (5-6) ◽  
pp. 391-394 ◽  
Author(s):  
Manuel Gentiluomo ◽  
Ye Lu ◽  
Federico Canzian ◽  
Daniele Campa
Keyword(s):  
Pancreatic Cancer ◽  
Genetic Variability ◽  
Cancer Risk ◽  
Genetic Variants ◽  
Regulatory Elements ◽  
Taste Receptors ◽  
Data Set ◽  
Pancreatic Cancer Risk ◽  
Validation Phase ◽  
The Impact

Abstract Pancreatic ductal adenocarcinoma is an aggressive and relatively rare cancer with a dismal 5-year survival rate and a clear genetic background. Genetic variants in taste receptors and taste-related genes have been associated with a variety of human traits and phenotypes among which several cancer types and pancreatic cancer risk factors. In this study, we analysed 2854 single-nucleotide polymorphisms in 50 taste-related genes, including 37 taste receptors. To cover all the genetic variability of the selected genes and to include also regulatory elements, we added 5000 nucleotides to both ends of each gene. We used a two-phase approach, with the PanScan data set (3314 cases and 3431 controls) as the discovery phase and PanC4 (3893 cases and 3632 controls) as validation phase, for a total of 7207 cases and 7063 controls. The datasets were downloaded from the NCBI database of genotypes and phenotypes (dbGaP). We observed that the taste 1 receptor member 2 (TAS1R2)-rs11261087 variant was associated with pancreatic cancer risk in both phases independently, with a consistent association of the T allele with decreased risk of developing the disease [phase 1 odds ratio (OR) = 0.89, 95% confidence interval (CI) 0.80–0.98; phase 2 OR = 0.91, 95% CI 0.83–0.99; all subjects together OR = 0.90, 95% CI 0.84–0.96, P = 0.002]. However, neither the association observed in the validation phase nor those observed in the joint analysis were statistically significant considering multiple testing. Functional studies are warranted to better understand the impact of the genetic variability of TAS1R2 on PDAC risk.

scholarly journals A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer

2020 ◽  
Vol 112 (10) ◽  
pp. 1003-1012 ◽  
Author(s):  
Jun Zhong ◽  
Ashley Jermusyk ◽  
Lang Wu ◽  
Jason W Hoskins ◽  
Irene Collins ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Cancer Risk ◽  
Association Study ◽  
Association Studies ◽  
Tissue Expression ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Pancreatic Cancer Risk ◽  
Genome Wide

Abstract Background Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. Methods To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74–421 samples). Results We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate &lt; .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at six known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction. Conclusions By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.

Identification of genetic variants in m6A modification genes associated with pancreatic cancer risk in the Chinese population

2021 ◽  
Vol 95 (3) ◽  
pp. 1117-1128
Author(s):  
Pingting Ying ◽  
Yao Li ◽  
Nan Yang ◽  
Xiaoyang Wang ◽  
Haoxue Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Risk ◽  
Genetic Variants ◽  
Chinese Population ◽  
Pancreatic Cancer Risk

scholarly journals Traditional and Novel Adiposity Indicators and Pancreatic Cancer Risk: Findings from the UK Women’s Cohort Study

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1036
Author(s):  
Sangeetha Shyam ◽  
Darren Greenwood ◽  
Chun-Wai Mai ◽  
Seok Shin Tan ◽  
Barakatun Nisak Mohd Yusof ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cohort Study ◽  
Cancer Risk ◽  
Reverse Causality ◽  
Hip Circumference ◽  
Primary Analysis ◽  
Pancreatic Cancer Risk ◽  
Obesity Indices ◽  
The Uk

(1) Background: We studied the association of both conventional (BMI, waist and hip circumference and waist–hip ratio) and novel (UK clothing sizes) obesity indices with pancreatic cancer risk in the UK women’s cohort study (UKWCS). (2) Methods: The UKWCS recruited 35,792 women from England, Wales and Scotland from 1995 to 1998. Cancer diagnosis and death information were obtained from the National Health Service (NHS) Central Register. Cox’s proportional hazards regression was used to evaluate the association between baseline obesity indicators and pancreatic cancer risk. (3) Results: This analysis included 35,364 participants with a median follow-up of 19.3 years. During the 654,566 person-years follow up, there were 136 incident pancreatic cancer cases. After adjustments for age, smoking, education and physical activity, each centimetre increase in hip circumference (HR: 1.03, 95% CI: 1.01–1.05, p = 0.009) and each size increase in skirt size (HR: 1.12, 95% CI: 1.02–1.23, p = 0.041) at baseline increased pancreatic cancer risk. Baseline BMI became a significant predictor of pancreatic cancer risk (HR: 1.04, 95% CI: 1.00–1.08, p = 0.050) when latent pancreatic cancer cases were removed. Only baseline hip circumference was associated with pancreatic cancer risk (HR: 1.03, 95% CI: 1.00–1.05, p = 0.017) when participants with diabetes at baseline were excluded to control for reverse causality. (4) Conclusion: Hip circumference and skirt size were significant predictors of pancreatic cancer risk in the primary analysis. Thus, hip circumference is useful to assess body shape relationships. Additionally, standard skirt sizes offer an economical and objective alternative to conventional obesity indices for evaluating pancreatic cancer risk in women.

scholarly journals MDM2 Promoter Polymorphism and Pancreatic Cancer Risk and Prognosis

2008 ◽  
Vol 14 (12) ◽  
pp. 4010-4015 ◽  
Author(s):  
Kofi Asomaning ◽  
Amy E. Reid ◽  
Wei Zhou ◽  
Rebecca S. Heist ◽  
Rihong Zhai ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Risk ◽  
Promoter Polymorphism ◽  
Pancreatic Cancer Risk
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