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Risk Factors for Sporadic Pancreatic Neuroendocrine Tumors: A Case-Control Study.

ABSTRACT: The current study examined risk factors for sporadic pancreatic neuroendocrine tumors (PNETs), including smoking, alcohol use, first-degree family history of any cancer (FHC), and diabetes in the Han Chinese ethnic group. In this clinic-based case-control analysis on 385 patients with sporadic PNETs and 614 age- and sex-matched controls, we interviewed subjects using a specific questionnaire on demographics and potential risk factors. An unconditional multivariable logistic regression analysis was used to estimate adjusted odds ratios (AORs). No significant differences were found between patients and controls in terms of demographic variables. Most of the patients with PNETs had well-differentiated PNETs (G1, 62.9%) and non-advanced European Neuroendocrine Tumor Society (ENETS) stage (stage I or II, 83.9%). Ever/heavy smoking, a history of diabetes and a first-degree FHC were independent risk factors for non-functional PNETs. Only heavy drinking was found to be an independent risk factor for functional PNETs (AOR?=?1.87; 95% confidence interval [CI], 1.01-3.51). Ever/heavy smoking was also associated with advanced ENETS staging (stage III or IV) at the time of diagnosis. This study identified first-degree FHC, ever/heavy smoking, and diabetes as risk factors for non-functional PNETs, while heavy drinking as a risk factor for functional PNETs.

SUBMITTER: Ben Q

PROVIDER: S-EPMC5080551 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Risk Factors for Sporadic Pancreatic Neuroendocrine Tumors: A Case-Control Study.

Ben Qiwen Q Zhong Jie J Fei Jian J Chen Haitao H Yv Lifen L Tan Jihong J Yuan Yaozong Y

Scientific reports 20161026

The current study examined risk factors for sporadic pancreatic neuroendocrine tumors (PNETs), including smoking, alcohol use, first-degree family history of any cancer (FHC), and diabetes in the Han Chinese ethnic group. In this clinic-based case-control analysis on 385 patients with sporadic PNETs and 614 age- and sex-matched controls, we interviewed subjects using a specific questionnaire on demographics and potential risk factors. An unconditional multivariable logistic regression analysis w ...[more]

PMID: 27782199

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Project description:BackgroundNonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) may be sporadic or inherited because of germline mutations associated with von Hippel-Lindau disease (VHL) or multiple endocrine neoplasia type 1 (MEN1). The clinical behavior of NFPanNETs is difficult to predict, even in tumors of the same stage and grade. The authors analyzed genotype-specific patterns of transcriptional messenger RNA (mRNA) levels of NFPanNETs to understand the molecular features that determine PanNET phenotype.MethodsThirty-two samples were included for genome-wide mRNA gene expression analysis (9 VHL-associated, 10 MEN1-associated, and 9 sporadic NFPanNETs and 4 purified normal islet cell [NIC] samples). Validation of genes was performed by real-time polymerase chain reaction analysis and immunohistochemistry. Gene expression profiles were analyzed by tumor genotype, and pathway analysis was curated.ResultsConsensus clustering of mRNA expression revealed separate clustering of NICs, VHL-associated NFPanNETs, and MEN1-associated NFPanNETs; whereas some sporadic tumors clustered with MEN1. Four of 5 MEN1-like sporadic PanNET subtypes had loss of heterozygosity at the MEN1 gene locus. Pathway analysis demonstrated subtype-specific pathway activation, comprising angiogenesis and immune response in VHL; neuronal development in MEN1; protein ubiquitination in the new MEN1/sporadic subtype; and cytokinesis and cilium/microtubule development in sporadic NFPanNETs. Among many genes, platelet-derived growth factor receptor β (PDGFRB), lymphoid enhancer-binding factor-1 (Lef-1), cyclin-dependent kinase 4 (CDK4), and CDK6 were upregulated in VHL or MEN1 NFPanNETs, providing potential subtype-specific treatment targets.ConclusionsDistinct mRNA expression patterns were identified in sporadic-associated, VHL-associated, and MEN1-associated NFPanNETs. The current results uncover new pathways involved in NFPanNETs that are subtype-specific and provide potential new diagnostic or therapeutic targets based on tumor subtype. Cancer 2018;124:636-47. © 2017 American Cancer Society.

Dataset Information

Risk Factors for Sporadic Pancreatic Neuroendocrine Tumors: A Case-Control Study.

Publications

Risk Factors for Sporadic Pancreatic Neuroendocrine Tumors: A Case-Control Study.

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