@article{cedef63e1c5a4538bf02a25bf8d3bb38,
title = "Genetic variants in microRNAs and breast cancer risk in African American and European American women",
abstract = "MicroRNAs (miRNAs) are an integral part of the post-transcriptional machinery of gene expression and have been implicated in the carcinogenic cascade. Single nucleotide polymorphisms (SNPs) in miRNAs and risk of breast cancer have been evaluated in populations of European or Asian ancestry, but not among women of African ancestry. Here we examined 145 SNPs in six miRNA processing genes and in 78 miRNAs which target genes known to be important in breast cancer among 906 African American (AA) and 653 European American (EA) cases and controls enrolled in the Women's Circle of Health Study. Allele frequencies of most SNPs (87 %) differed significantly by race. We found a number of SNPs in miRNAs and processing genes in association with breast cancer overall or stratified by estrogen receptor (ER) status. Several associations were significantly different by race, with none of the associations being significant in both races. Using a polygenic risk score to combine the effects of multiple SNPs, we found significant associations with the score in each subgroup analysis. For ER-positive cancer, each unit increment of the risk score was associated with a 51 % increased risk in AAs (OR = 1.51, 95 % CI = 1.30-1.74, p = 3.3 × 10-8) and a 73 % increased risk in EAs (OR = 1.73, 95 % CI = 1.45-2.06, p = 1.4 × 10-9). These data show, for the first time, that miRNA-related genetic variations may underlie the etiology of breast cancer in both populations of African and European ancestries. Future studies are needed to validate our findings and to explore the underlying mechanisms.",
keywords = "Breast cancer, Epidemiology, Estrogen receptor, MicroRNA, Polygenic risk score, SNP",
author = "Song Yao and Kelly Graham and Jie Shen and Campbell, {Lara E Sucheston} and Prashant Singh and Gary Zirpoli and Michelle Roberts and Gregory Ciupak and Warren Davis and Helena Hwang and Thaer Khoury and Bovbjerg, {Dana H.} and Lina Jandorf and Pawlish, {Karen S.} and Bandera, {Elisa V.} and Song Liu and Ambrosone, {Christine B.} and Hua Zhao",
note = "Funding Information: Acknowledgments This work was supported by grants from the U.S. Army Medical Research and Material Command (USARMMC) (DAMD-17-01-1-0334 and W81XWH-08-1-0379), the National Cancer Institute (R01 CA100598, R01 CA136483 and R25 CA114101), the Breast Cancer Research Foundation and a gift from Philip L. Hubbell family. Samples were stored and managed by the RPCI DataBank and BioRepository (DBBR) and genotyping was performed in the RPCI Genomics Core Facility, both CCSG shared resources, supported by P30 CA016056-32. The New Jersey State Cancer Registry (NJSCR) is a participant in the Centers for Disease Control and Prevention{\textquoteright}s National Program of Cancer Registries (NPCR) and is a National Cancer Institute SEER Expansion Registry. The NJSCR is supported by the Centers for Disease Control and Prevention under cooperative agreement 1U58DP00039311-01 awarded to the New Jersey Department of Health. The collection of State of New Jersey cancer incidence data is also supported by the National Cancer Institute{\textquoteright}s Surveillance, Epidemiology, and End Results (SEER) Program under contract N01-PC-2010-00027 and the State of New Jersey. The funding agents played no role in design, in the collection, analysis, and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication. We are grateful to the women who participated in this study, and to colleagues, physicians, and clinical staff at participating hospitals in New York who facilitated identification and enrollment of cases into the study: Drs. Kandace Amend (i3 Drug Safety), Helena Furberg (Memorial Sloan-Kettering Cancer Center), Thomas Rohan and Joseph Sparano (Albert Einstein College of Medicine), Kitwaw De-missie (University of Medicine and Dentistry of New Jersey), Paul Tartter and Alison Estabrook (St. Luke{\textquoteright}s Roosevelt Hospital), James Reilly (Kings County Hospital Center), Benjamin Pace, George Raptis and Christina Weltz (Mount Sinai School of Medicine), Maria Castaldi (Jacob Medical Center), Sheldon Feldman (New York-Presbyterian), and Margaret Kemeny (Queens Hospital Center).",
year = "2013",
month = oct,
doi = "10.1007/s10549-013-2698-4",
language = "English (US)",
volume = "141",
pages = "447--459",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "3",
}