TY - JOUR
T1 - Common and rare sequence variants influencing tumor biomarkers in blood
AU - Olafsson, Sigurgeir
AU - Alexandersson, Kristjan F.
AU - Gizurarson, Johann G.K.
AU - Hauksdottir, Katrin
AU - Gunnarsson, Orvar
AU - Olafsson, Karl
AU - Gudmundsson, Julius
AU - Stacey, Simon N.
AU - Sveinbjornsson, Gardar
AU - Saemundsdottir, Jona
AU - Bjornsson, Einar S.
AU - Olafsson, Sigurdur
AU - Bjornsson, Sigurdur
AU - Orvar, Kjartan B.
AU - Vikingsson, Arnor
AU - Geirsson, Arni J.
AU - Arinbjarnarson, Sturla
AU - Bjornsdottir, Gyda
AU - Thorgeirsson, Thorgeir E.
AU - Sigurdsson, Snaevar
AU - Halldorsson, Gisli H.
AU - Magnusson, Olafur T.
AU - Masson, Gisli
AU - Holm, Hilma
AU - Jonsdottir, Ingileif
AU - Sigurdardottir, Olof
AU - Eyjolfsson, Gudmundur I.
AU - Olafsson, Isleifur
AU - Sulem, Patrick
AU - Thorsteinsdottir, Unnur
AU - Jonsson, Thorvaldur
AU - Rafnar, Thorunn
AU - Gudbjartsson, Daniel F.
AU - Stefansson, Kari
N1 - The authors would like to acknowledge the work of the staff of the genotyping and informatics facilities in deCODE Genetics and of the Icelandic Cancer registry, without whom this study would not have been possible. This study was funded by deCODE Genetics/Amgen and supported in part by the National Institute of Dental and Craniofacial Research of the National Institutes of Health, under award number R01DE022905, awarded to K. Stefansson. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Publisher Copyright: © 2020 American Association for Cancer Research.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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 ¼ 22,686), carcinoembryonic antigen (N ¼ 22,309), cancer antigens 15.3 (N ¼ 7,107), 19.9 (N ¼ 9,945), and 125 (N ¼ 9,824), and ALP (N ¼ 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.
AB - 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 ¼ 22,686), carcinoembryonic antigen (N ¼ 22,309), cancer antigens 15.3 (N ¼ 7,107), 19.9 (N ¼ 9,945), and 125 (N ¼ 9,824), and ALP (N ¼ 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.
KW - Krabbameinslækningar
UR - https://www.scopus.com/pages/publications/85077925851
U2 - 10.1158/1055-9965.EPI-18-1060
DO - 10.1158/1055-9965.EPI-18-1060
M3 - Article
C2 - 31666285
SN - 1055-9965
VL - 29
SP - 225
EP - 235
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
ER -
