Variants in SNAI1, AMDHD1 and CUBN in vitamin D pathway genes are associated with breast cancer risk: a large-scale analysis of 14 GWASs in the DRIVE study.


Vitamin D has a potential anticarcinogenic role, possibly through regulation of cell proliferation and differentiation, stimulation of apoptosis, immune modulation and regulation of estrogen receptor levels. Because breast cancer (BC) risk varies among individuals exposed to similar risk factors, we hypothesize that genetic variants in the vitamin D pathway genes are associated with BC risk. To test this hypothesis, we performed a larger meta-analysis using 14 published GWAS datasets in the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Study. We assessed associations between 2,994 (237 genotyped in the DRIVE study and 2,757 imputed from the 1000 Genomes Project) single nucleotide polymorphisms (SNPs) in 33 vitamin D pathway genes and BC risk. In unconditional logistic regression analysis, we found 11 noteworthy SNPs to be associated with BC risk after multiple comparison correction by the Bayesian false-discovery probability method (<0.80). In stepwise logistic regression analysis, with adjustment for age, principal components and previously published SNPs in the same study populations, we identified three independent SNPs (SNAI1 rs1047920 C>T, AMDHD1 rs11826 C>T and CUBN rs3914238 C>T) to be associated with BC risk (P = 0.0014, 0.0020 and 0.0022, respectively). Additional expression quantitative trait loci analysis revealed that the rs73276407 A allele, in a high LD with the rs1047920 T allele, was associated with decreased SNAI1 mRNA expression levels, while the rs11826 T allele was significantly associated with elevated AMDHD1 mRNA expression levels. Once replicated by other investigators and additional mechanistic studies, these genetic variants may serve as new biomarkers for susceptibility to BC.







Sheng Luo

Professor of Biostatistics & Bioinformatics

Tomi Akinyemiju

Professor in Population Health Sciences

Area of Expertise: Epidemiology

Dr. Akinyemiju is a Professor of Population Health Sciences, Global Health and Ob/Gyn with expertise in cancer epidemiology, cancer biology, global health, and health disparities.  Her research expertise and accomplishments have focused on articulating and innovating conceptual and empirical approaches for cancer health disparities research, specifically, disentangling the role of race as a social construct and race-associated biological mechanisms that contribute to cancer disparities. Dr. Akinyemiju also serves as the Vice-Chair for Diversity, Equity, and Inclusion at the Department of Population Health Sciences, and Associate Director for Community Outreach, Engagement, and Equity at the Duke Cancer Institute. Dr. Akinyemiju’s leadership centers around building cross-enterprise, multi-stakeholder coalitions to advance health equity, promote inclusion and diversity, and mentor the next generation of diverse, talented clinical research scholars. Dr. Akinyemiju has received numerous awards, including the 2023 Michelle Winn Inclusive Excellence Award

Dr. Akinyemiju has published over 150 peer-reviewed publications, and her research program has been continuously funded by the National Institutes of Health, Susan G. Komen and the V Foundation. She has mentored (formally and informally) at least 50 trainees and junior faculty, over 50% of whom are URM. Dr. Akinyemiju works extensively with diverse stakeholders, including community-based organizations, policy makers, providers, health system leadership, and leaders from diverse communities to develop impactful, evidence-based interventions to advance health equity 


Qingyi Wei

Professor Emeritus in Population Health Sciences

Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally recognized epidemiologist focused on the molecular and genetic epidemiology of head and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and genetic determinants for the DNA repair deficient phenotype and variations in cell death. He is Editor-in-Chief of the open access journal "Cancer Medicine" and Associate Editor-in-Chief of the International Journal of Molecular Epidemiology and Genetics.

Area of Expertise: Epidemiology

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