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Common and Rare Sequence Variants Influencing Tumor Biomarkers in Blood.


ABSTRACT:

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.

SUBMITTER: Olafsson S 

PROVIDER: S-EPMC6954334 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Common and Rare Sequence Variants Influencing Tumor Biomarkers in Blood.

Olafsson Sigurgeir S   Alexandersson Kristjan F KF   Gizurarson Johann G K JGK   Hauksdottir Katrin K   Gunnarsson Orvar O   Olafsson Karl K   Gudmundsson Julius J   Stacey Simon N SN   Sveinbjornsson Gardar G   Saemundsdottir Jona J   Bjornsson Einar S ES   Olafsson Sigurdur S   Bjornsson Sigurdur S   Orvar Kjartan B KB   Vikingsson Arnor A   Geirsson Arni J AJ   Arinbjarnarson Sturla S   Bjornsdottir Gyda G   Thorgeirsson Thorgeir E TE   Sigurdsson Snaevar S   Halldorsson Gisli H GH   Magnusson Olafur T OT   Masson Gisli G   Holm Hilma H   Jonsdottir Ingileif I   Sigurdardottir Olof O   Eyjolfsson Gudmundur I GI   Olafsson Isleifur I   Sulem Patrick P   Thorsteinsdottir Unnur U   Jonsson Thorvaldur T   Rafnar Thorunn T   Gudbjartsson Daniel F DF   Stefansson Kari K  

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20191030 1


<h4>Background</h4>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  ...[more]

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