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The Combined Effects of Single-Nucleotide Polymorphisms, Tobacco Products, and Ethanol on Normal Resting Blood Mononuclear Cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
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2013 (English)In: Nicotine & tobacco research, ISSN 1462-2203, E-ISSN 1469-994X, Vol. 15, no 5, 890-895 p.Article in journal (Refereed) Published
Abstract [en]

Introduction: Tobacco and ethanol consumption are crucial factors in the development of various diseases including cancer. In this investigation, we evaluated the combined effects of a number of single nucleotide polymorphisms (SNPs), with ethanol and tobacco products on healthy individuals. Methods: Pure nicotine, cigarette smoke extract, and Swedish snuff (snus) extract were used. The effects were examined by means of in vitro cell cycle progression and cell death of peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. Results: After 3 days, in vitro, resting PBMCs entered the S and G2 stage in the presence of 100 mu M nicotine. The PBMCs only proceeded to S stage, in the presence of 0.2% ethanol. The nicotine- and ethanol-induced normal cell cycle progression correlated to a number of SNPs in the IL12RB2, Rad 52, XRCC2, P53, CCND3, and ABCA1 genes. Certain SNPs in Caspases 8, IL12RB2, Rad 52, MMP2, and MDM2 genes appeared to significantly influence the effects of EtOH-, snus-, and snus + EtOH-induced cell death. Importantly, the highest degree of cell death was observed in the presence of smoke + EtOH. The amount of cell death under this treatment condition also correlated to specific SNPs, located in the MDM2, ABCA1, or GASC1 genes. Conclusions: Cigarette smoke in combination with ethanol strongly induced massive cell death. Long-term exposure to smoke and ethanol could provoke chronic inflammation, and this could be the initiation of disease including the development of cancer at various sites.

Place, publisher, year, edition, pages
2013. Vol. 15, no 5, 890-895 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-200343DOI: 10.1093/ntr/nts207ISI: 000317796500004OAI: oai:DiVA.org:uu-200343DiVA: diva2:623627
Available from: 2013-05-28 Created: 2013-05-27 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Aspects on Head and neck Cancer with special reference to Salivary Gland Tumours and Single Nucleotide Polymorphism
Open this publication in new window or tab >>Aspects on Head and neck Cancer with special reference to Salivary Gland Tumours and Single Nucleotide Polymorphism
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A thesis on Head and neck cancer focusing on dose planning, salivary gland carcinoma and Single nucleotide polymorphism.

For dose planning PET/CT (Positron emissions tomography/computed tomography) with tracer gave more precise information in comparison dose planning with CT. More primary tumours and metastases were found with the acetate tracer than with glucose tracer. Acetate PET/CT also showed larger volume of tumours attributed to lipid metabolism.

In a retrospective study salivary gland cancer 5-year overall survival (OS) was 53 %. Salivary gland carcinoma consists of many histopathological groups, the two largest groups being mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ASCC). For ACC, having the best 5-year OS, it was 70 percent. Facial palsy, advanced stage disease, lymph node metastases worsened prognosis. ACC and polymorphous low grade carcinoma (PLGA) expressed c-myc and cyclin D1 to a larger extent than MEC.

In squamous cell carcinoma of the head and neck we examined the occurrence of Single Nucleotide polymorphism, SNP. We found that the SNPs in male and female patients differed from each other. In male patients the SNPs were associated with immune response while in female patients the association was to SNPs concerning inflammation. This means that different pathways were engaged in cancer development for men and women. We also found that the SNPs in patients were different from those expressed in the healthy controls.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 47 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1390
Keyword
salivary gland carcinoma, adenoid cystic, mucoepidermoid, polymorphous low-grade carinoma, c-myc, cyclin D1, perineural
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-332192 (URN)978-91-513-0130-3 (ISBN)
Public defence
2017-12-14, Skoogsalen, ingång 78/79 pl 1, Akademiska sjukhuset, Uppsala, 09:00 (Swedish)
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Available from: 2017-11-20 Created: 2017-10-25 Last updated: 2017-11-20

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Cederblad, LenaThunberg, UlfEngström, MatsLaytragoon-Lewin, Nongnit

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