ArticlePLoS genetics2019
A region-based gene association study combined with a leave-one-out sensitivity analysis identifies SMG1 as a pancreatic cancer susceptibility gene.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- The causal relationship between 179 lipid species and urolithiasis: a bidirectional and multivariable Mendelian randomization study combined with meta-analysis.Lipids in health and disease · 2025Pooled it
- Investigating the Impact of Curcumin on the Methylation of DNMT1, CDH1, SMG1, and WT1 Genes in the MIAPaCa2 Cell Line Using High-Resolution Melting Analysis Compared to Methylation-Specific PCR.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- Established Cancer Predisposition Genes in Single and Multiple Cancer Diagnoses.JAMA oncology · 2025Article
- Age at first sexual intercourse, age at menarche, and age at menopause: a mendelian randomization study on lung cancer risk.Translational lung cancer research · 2024Article
- Association of obstructive sleep apnea syndrome with polycystic ovary syndrome through bidirectional Mendelian randomization.Frontiers in medicine · 2024Article
- Association of Barrett's esophagus with obstructive sleep apnea syndrome: a bidirectional analysis of Mendelian randomization.Frontiers in psychiatry · 2023Article
- Aberrant DNA Methylation Status and mRNA Expression Level of SMG1 Gene in Chronic Myeloid Leukemia: A Case-Control Study.Cell journal · 2022Article
- Intra-Tumoral CD8+ T-Cell Infiltration and PD-L1 Positivity in Homologous Recombination Deficient Pancreatic Ductal Adenocarcinoma.Frontiers in oncology · 2022Article
- The genetics of ductal adenocarcinoma of the pancreas in the year 2020: dramatic progress, but far to go.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Review
- Circular RNA VMA21 ameliorates sepsis-associated acute kidney injury by regulating miR-9-3p/SMG1/inflammation axis and oxidative stress.Journal of cellular and molecular medicine · 2020Article
- Identification of NovelFrontiers in genetics · 2020Article
- Circulating metabolites mediate the effects of lipids on Alzheimer's disease: A Mendelian randomization and mediation analysis.Journal of Alzheimer's disease reportsArticle
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Authors and funding
24 authors at 10 institutions in 2 countries.
Funding
Abstract
Pancreatic adenocarcinoma (PC) is a lethal malignancy that is familial or associated with genetic syndromes in 10% of cases. Gene-based surveillance strategies for at-risk individuals may improve clinical outcomes. However, familial PC (FPC) is plagued by genetic heterogeneity and the genetic basis for the majority of FPC remains elusive, hampering the development of gene-based surveillance programs. The study was powered to identify genes with a cumulative pathogenic variant prevalence of at least 3%, which includes the most prevalent PC susceptibility gene, BRCA2. Since the majority of known PC susceptibility genes are involved in DNA repair, we focused on genes implicated in these pathways. We performed a region-based association study using the Mixed-Effects Score Test, followed by leave-one-out characterization of PC-associated gene regions and variants to identify the genes and variants driving risk associations. We evaluated 398 cases from two case series and 987 controls without a personal history of cancer. The first case series consisted of 109 patients with either FPC (n = 101) or PC at ≤50 years of age (n = 8). The second case series was composed of 289 unselected PC cases. We validated this discovery strategy by identifying known pathogenic BRCA2 variants, and also identified SMG1, encoding a serine/threonine protein kinase, to be significantly associated with PC following correction for multiple testing (p = 3.22x10-7). The SMG1 association was validated in a second independent series of 532 FPC cases and 753 controls (p<0.0062, OR = 1.88, 95%CI 1.17-3.03). We showed segregation of the c.4249A>G SMG1 variant in 3 affected relatives in a FPC kindred, and we found c.103G>A to be a recurrent SMG1 variant associating with PC in both the discovery and validation series. These results suggest that SMG1 is a novel PC susceptibility gene, and we identified specific SMG1 gene variants associated with PC risk.
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Registered trials
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