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Cancer Epidemiol Biomarkers Prev. 2019 Oct 30. pii: cebp.1060.2018. doi: 10.1158/1055-9965.EPI-18-1060. [Epub ahead of print]

Common and rare sequence variants influencing tumor biomarkers in blood.

Author information

1
deCODE genetics/AMGEN.
2
Statistics, deCODE genetics/AMGEN.
3
Population Genetics, deCODE genetics/AMGEN.
4
Hematology and Oncology, Landspitali, The National University Hospital of Iceland.
5
Department of Medicine, Landspitali - The National University Hospital of Iceland.
6
Cancer, deCODE Genetics (Iceland).
7
Faculty of medicine, University of Iceland.
8
Medicine, Landspitali, The National University Hospital of Iceland.
9
Glæsibær, The Laboratory of the Medical Clinic Glaesibae.
10
Population Genomics, CNS dpt, deCODE genetics/AMGEN.
11
Population genomics, deCODE Genetics (Iceland).
12
Genetics, deCODE genetics/AMGEN.
13
Department of Clinical Biochemistry, Akureyri Hospital.
14
Icelandic Medical Center (Laeknasetrid), Laboratory in Mjodd (RAM).
15
Department of Clinical Biochemistry, Landspitali, The National University Hospital of Iceland.
16
Statistics, deCODE Genetics (Iceland).
17
deCODE genetics/AMGEN daniel.gudbjartsson@decode.is.

Abstract

BACKGROUND:

Alpha-fetoprotein, cancer antigens 15.3, 19.9, 125, carcinoembryonic antigen and alkaline phosphatase 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 non-malignant 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 alpha-fetoprotein (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 alkaline phosphatase (N = 162,774). We also examined the correlations between levels of these biomarkers and the presence of cancer, using data from a nation-wide 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.

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