ArticleCarcinogenesis2014
Axonal guidance signaling pathway interacting with smoking in modifying the risk of pancreatic cancer: a gene- and pathway-based interaction analysis of GWAS data.
Article in Carcinogenesis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- Genetic variants in the platelet-derived growth factor subunit B gene associated with pancreatic cancer risk.International journal of cancer · 2018Pooled it
- Associations between Nine Polymorphisms in EXO1 and Cancer Susceptibility: A Systematic Review and Meta-Analysis of 39 Case-control Studies.Scientific reports · 2016Pooled it
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- Causal Relationships Between Environmental Exposures, Iron Metabolism, Hematuria Markers, and Rheumatoid Arthritis: An Investigation Using Mendelian Randomization.Biomedicines · 2025Article
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- Prognostic evaluation of pancreatic cancer based on the model of chemo-radiotherapy resistance-related genes.Journal of gastrointestinal oncology · 2023Article
- Identification of novel susceptibility methylation loci for pancreatic cancer in a two-phase epigenome-wide association study.Epigenetics · 2022Article
- ROBO1 protein expression is independently associated with biochemical recurrence in prostate cancer patients who underwent radical prostatectomy in Asian patients.Gland surgery · 2021Article
- Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3.Cancer research · 2021Article
- Incorporating multiple sets of eQTL weights into gene-by-environment interaction analysis identifies novel susceptibility loci for pancreatic cancer.Genetic epidemiology · 2020Article
- Multi-omics Data Analyses Construct TME and Identify the Immune-Related Prognosis Signatures in Human LUAD.Molecular therapy. Nucleic acids · 2020Article
- Genome-Wide Gene-Diabetes and Gene-Obesity Interaction Scan in 8,255 Cases and 11,900 Controls from PanScan and PanC4 Consortia.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Article
- ZBED2 is an antagonist of interferon regulatory factor 1 and modifies cell identity in pancreatic cancer.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- A powerful and data-adaptive test for rare-variant-based gene-environment interaction analysis.Statistics in medicine · 2019Article
- Molecular mechanisms of Ellis‑van Creveld gene variations in ventricular septal defect.Molecular medicine reports · 2018Article
- Incorporation of Biological Knowledge Into the Study of Gene-Environment Interactions.American journal of epidemiology · 2017Article
- Validity of using ad hoc methods to analyze secondary traits in case-control association studies.Genetic epidemiology · 2016Article
- Genome-wide association studies and epigenome-wide association studies go together in cancer control.Future oncology (London, England) · 2016Article
- Influence of a single-nucleotide polymorphism of the DNA mismatch repair-related gene exonuclease-1 (rs9350) with prostate cancer risk among Chinese people.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
Corrections and comments
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Authors and funding
23 authors at 19 institutions in 11 countries.
Funding
Abstract
Cigarette smoking is the best established modifiable risk factor for pancreatic cancer. Genetic factors that underlie smoking-related pancreatic cancer have previously not been examined at the genome-wide level. Taking advantage of the existing Genome-wide association study (GWAS) genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study in 2028 cases and 2109 controls to examine gene-smoking interactions at pathway/gene/single nucleotide polymorphism (SNP) level. Using the likelihood ratio test nested in logistic regression models and ingenuity pathway analysis (IPA), we examined 172 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, 3 manually curated gene sets, 3 nicotine dependency gene ontology pathways, 17 912 genes and 468 114 SNPs. None of the individual pathway/gene/SNP showed significant interaction with smoking after adjusting for multiple comparisons. Six KEGG pathways showed nominal interactions (P < 0.05) with smoking, and the top two are the pancreatic secretion and salivary secretion pathways (major contributing genes: RAB8A, PLCB and CTRB1). Nine genes, i.e. ZBED2, EXO1, PSG2, SLC36A1, CLSTN1, MTHFSD, FAT2, IL10RB and ATXN2 had P interaction < 0.0005. Five intergenic region SNPs and two SNPs of the EVC and KCNIP4 genes had P interaction < 0.00003. In IPA analysis of genes with nominal interactions with smoking, axonal guidance signaling $$\left(P=2.12\times 1{0}^{-7}\right)$$ and α-adrenergic signaling $$\left(P=2.52\times 1{0}^{-5}\right)$$ genes were significantly overrepresented canonical pathways. Genes contributing to the axon guidance signaling pathway included the SLIT/ROBO signaling genes that were frequently altered in pancreatic cancer. These observations need to be confirmed in additional data set. Once confirmed, it will open a new avenue to unveiling the etiology of smoking-associated pancreatic cancer.
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