Associations between genetically predicted circulating protein concentrations and endometrial cancer risk

Zhu J, O’mara TA, Liu D, Setiawan VW, Glubb D, Spurdle AB, Fasching P, Lambrechts D, Buchanan D, Kho PF, Cook LS, Friedenreich C, Lacey JV, Chen C, Wentzensen N, De Vivo I, Sun Y, Long J, Du M, Shu XO, Zheng W, Wu L, Yu H (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Cancers MDPI

Book Volume: 13

Article Number: 2088

Journal Issue: 9

DOI: 10.3390/cancers13092088

Abstract

Endometrial cancer (EC) is the leading female reproductive tract malignancy in developed countries. Currently, genome-wide association studies (GWAS) have identified 17 risk loci for EC. To identify novel EC-associated proteins, we used previously reported protein quantitative trait loci for 1434 plasma proteins as instruments to evaluate associations between genetically predicted circulating protein concentrations and EC risk. We studied 12,906 cases and 108,979 controls of European descent included in the Endometrial Cancer Association Consortium, the Epidemiology of Endometrial Cancer Consortium, and the UK Biobank. We observed associations between genetically predicted concentrations of nine proteins and EC risk at a false discovery rate of <0.05 (p-values range from 1.14 × 10−10 to 3.04 × 10−4). Except for vascular cell adhesion protein 1, all other identified proteins were independent from known EC risk variants identified in EC GWAS. The respective odds ratios (95% confidence intervals) per one standard deviation increase in genetically predicted circulating protein concentrations were 1.21 (1.13, 1.30) for DNA repair protein RAD51 homolog 4, 1.27 (1.14, 1.42) for desmoglein-2, 1.14 (1.07, 1.22) for MHC class I polypeptide-related sequence B, 1.05 (1.02, 1.08) for histo-blood group ABO system transferase, 0.77 (0.68, 0.89) for intestinal-type alkaline phosphatase, 0.82 (0.74, 0.91) for carbohydrate sulfotransferase 15, 1.07 (1.03, 1.11) for D-glucuronyl C5-epimerase, and 1.07 (1.03, 1.10) for CD209 antigen. In conclusion, we identified nine potential EC-associated proteins. If validated by additional studies, our findings may contribute to understanding the pathogenesis of endometrial tumor development and identifying women at high risk of EC along with other EC risk factors and biomarkers.

Authors with CRIS profile

Peter Fasching Professur für Translationale Frauenheilkunde und Geburtshilfe

Involved external institutions

University of Hawaiʻi at Mānoa US United States (USA) (US) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) AU Australia (AU) Keck School of Medicine of USC US United States (USA) (US) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven BE Belgium (BE) The University of Melbourne AU Australia (AU) University of New Mexico (UNM) / Universidad de Nuevo México US United States (USA) (US) Alberta Health Services (AHS) CA Canada (CA) City of Hope Medical Center US United States (USA) (US) Fred Hutchinson Cancer Research Center US United States (USA) (US) National Cancer Institute (NCI) US United States (USA) (US) Harvard T.H. Chan School of Public Health US United States (USA) (US) Vanderbilt University Medical Center US United States (USA) (US) Memorial Sloan Kettering Cancer Center US United States (USA) (US)

How to cite

APA:

Zhu, J., O’mara, T.A., Liu, D., Setiawan, V.W., Glubb, D., Spurdle, A.B.,... Yu, H. (2021). Associations between genetically predicted circulating protein concentrations and endometrial cancer risk. Cancers, 13(9). https://doi.org/10.3390/cancers13092088

MLA:

Zhu, Jingjing, et al. "Associations between genetically predicted circulating protein concentrations and endometrial cancer risk." Cancers 13.9 (2021).

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