Common and Rare Sequence Variants Influencing Tumor Biomarkers in Blood.

Autor:	Olafsson S; deCODE genetics/AMGEN, Reykjavik, Iceland., Alexandersson KF; deCODE genetics/AMGEN, Reykjavik, Iceland., Gizurarson JGK; deCODE genetics/AMGEN, Reykjavik, Iceland., Hauksdottir K; deCODE genetics/AMGEN, Reykjavik, Iceland., Gunnarsson O; Department of Oncology, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland., Olafsson K; Department of Obstetrics and Gynecology, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland., Gudmundsson J; deCODE genetics/AMGEN, Reykjavik, Iceland., Stacey SN; deCODE genetics/AMGEN, Reykjavik, Iceland., Sveinbjornsson G; deCODE genetics/AMGEN, Reykjavik, Iceland., Saemundsdottir J; deCODE genetics/AMGEN, Reykjavik, Iceland., Bjornsson ES; Department of Medicine, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland.; Faculty of Medicine, University of Iceland, Reykjavik, Iceland., Olafsson S; Department of Medicine, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland.; Division of Gastroenterology and Hepatology, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland., Bjornsson S; Department of Medicine, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland.; The Medical Center, Glaesibae, Reykjavik, Iceland., Orvar KB; Department of Medicine, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland.; The Medical Center, Glaesibae, Reykjavik, Iceland., Vikingsson A; Department of Medicine, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland.; Thraut Fibromyalgia Clinic, Reykjavik, Iceland., Geirsson AJ; Department of Medicine, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland.; Center for Rheumatology Research, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland.; Icelandic Medical Center (Laeknasetrid), Laboratory in Mjodd (RAM), Reykjavik, Iceland., Arinbjarnarson S; The Laboratory of the Medical Clinic Glaesibae, Reykjavik, Iceland., Bjornsdottir G; deCODE genetics/AMGEN, Reykjavik, Iceland., Thorgeirsson TE; deCODE genetics/AMGEN, Reykjavik, Iceland., Sigurdsson S; deCODE genetics/AMGEN, Reykjavik, Iceland., Halldorsson GH; deCODE genetics/AMGEN, Reykjavik, Iceland., Magnusson OT; deCODE genetics/AMGEN, Reykjavik, Iceland., Masson G; deCODE genetics/AMGEN, Reykjavik, Iceland., Holm H; deCODE genetics/AMGEN, Reykjavik, Iceland., Jonsdottir I; deCODE genetics/AMGEN, Reykjavik, Iceland.; Faculty of Medicine, University of Iceland, Reykjavik, Iceland., Sigurdardottir O; Department of Clinical Biochemistry, Akureyri Hospital, Akureyri, Iceland., Eyjolfsson GI; Icelandic Medical Center (Laeknasetrid), Laboratory in Mjodd (RAM), Reykjavik, Iceland., Olafsson I; Department of Clinical Biochemistry, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland., Sulem P; deCODE genetics/AMGEN, Reykjavik, Iceland., Thorsteinsdottir U; deCODE genetics/AMGEN, Reykjavik, Iceland.; Faculty of Medicine, University of Iceland, Reykjavik, Iceland., Jonsson T; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.; Department of Surgery, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland., Rafnar T; deCODE genetics/AMGEN, Reykjavik, Iceland., Gudbjartsson DF; deCODE genetics/AMGEN, Reykjavik, Iceland. daniel.gudbjartsson@decode.is.; School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland., Stefansson K; deCODE genetics/AMGEN, Reykjavik, Iceland.; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Jazyk:	angličtina
Zdroj:	Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology [Cancer Epidemiol Biomarkers Prev] 2020 Jan; Vol. 29 (1), pp. 225-235. Date of Electronic Publication: 2019 Oct 30.
DOI:	10.1158/1055-9965.EPI-18-1060
Abstrakt:	Background: Alpha-fetoprotein (AFP), cancer antigens 15.3, 19.9, and 125, carcinoembryonic antigen, and alkaline phosphatase (ALP) are widely measured in attempts to detect cancer and to monitor treatment response. However, due to lack of sensitivity and specificity, their utility is debated. The serum levels of these markers are affected by a number of nonmalignant factors, including genotype. Thus, it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. Methods: We performed genome-wide association studies of serum levels of AFP ( N = 22,686), carcinoembryonic antigen ( N = 22,309), cancer antigens 15.3 ( N = 7,107), 19.9 ( N = 9,945), and 125 ( N = 9,824), and ALP ( N = 162,774). We also examined the correlations between levels of these biomarkers and the presence of cancer, using data from a nationwide cancer registry. Results: We report a total of 84 associations of 79 sequence variants with levels of the six biomarkers, explaining between 2.3% and 42.3% of the phenotypic variance. Among the 79 variants, 22 are cis (in- or near the gene encoding the biomarker), 18 have minor allele frequency less than 1%, 31 are coding variants, and 7 are associated with gene expression in whole blood. We also find multiple conditions associated with higher biomarker levels. Conclusions: Our results provide insights into the genetic contribution to diversity in concentration of tumor biomarkers in blood. Impact: Genetic correction of biomarker values could improve prediction algorithms and decision-making based on these biomarkers. (©2019 American Association for Cancer Research.)
Databáze:	MEDLINE
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