The Role of Genetically Determined Glycemic Traits in Breast Cancer: A Mendelian Randomization Study

Su Yon Jung; Nicholas Mancuso; Sihao Han; Zuo-Feng Zhang

doi:10.3389/fgene.2020.540724

The Role of Genetically Determined Glycemic Traits in Breast Cancer: A Mendelian Randomization Study

Front Genet. 2020 Sep 16:11:540724. doi: 10.3389/fgene.2020.540724. eCollection 2020.

Authors

Su Yon Jung¹, Nicholas Mancuso^{2

3

4}, Sihao Han⁵, Zuo-Feng Zhang^{5

6}

Affiliations

¹ Translational Sciences Section, Jonsson Comprehensive Cancer Center, School of Nursing, University of California, Los Angeles, Los Angeles, CA, United States.
² Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
³ Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
⁴ Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, United States.
⁵ Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, United States.
⁶ Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.

Abstract

Background: Circulating glycemic traits (GTs) have been considered a risk factor for breast cancer, but studies using GT-associated genetic variants as an instrumental variable are limited and inconclusive.

Methods: Our Mendelian Randomization analysis used the most recent genome-wide datasets focusing on European women.

Results: Of 44 single-nucleotide polymorphisms (SNPs) with GTs, 38 fasting-glucose and 6 fasting-insulin SNPs showed heterogeneous associations with breast cancer, without significant directional pleiotropy observed.

Conclusion: Our findings indicate a null association between genetically determined GTs and breast cancer risk among European women. Our findings may contribute to more complete characterizing of metabolic pathways in GTs and breast cancer.

Keywords: Mendelian randomization; breast cancer; diabetes; genetically determined glucose and insulin; obesity.

Grants and funding

K01 NR017852/NR/NINR NIH HHS/United States