title: Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry.
abstract: MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR = 0.69, 95 % CI: 0.55-0.88, P = 0.003), ESR1 rs523736 (OR = 0.88, 95 % CI: 0.82-0.95, P = 3.99 × 10(-4)), and ZCCHC11 rs114101502 (OR = 1.33, 95 % CI: 1.11-1.59, P = 0.002), and one SNP in primary miRNA sequence (rs116159732 in miR-6826, OR = 0.74, 95 % CI: 0.63-0.89, P = 0.001) were found to have significant associations in both discovery and validation phases. In a subgroup analysis, two SNPs were associated with risk of estrogen receptor (ER)-negative breast cancer, and three SNPs were associated with risk of ER-positive breast cancer. Several variants in miRNA and miRNA biogenesis pathway genes were associated with breast cancer risk. Risk associations varied by ER status, suggesting potential new mechanisms in etiology.
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Qian
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: Yonglan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria.
authors.forename: Temidayo O
authors.initials: TO
authors.lastname: Ogundiran
authors.affiliation: Center for Population and Reproductive Health, College of Medicine, University of Ibadan, Ibadan, Nigeria.
authors.forename: Oladosu
authors.initials: O
authors.lastname: Ojengbede
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
authors.forename: William
authors.initials: W
authors.lastname: Blot
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
authors.affiliation: Cancer Prevention Institute of California, Fremont, CA, USA.|Department of Health Research and Policy (Epidemiology) and Stanford Cancer Institute, Stanford University School of Medicine Stanford, Stanford, CA, USA.
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
authors.affiliation: Division of Cancer Etiology, Department of Population Science, Beckman Research Institute, City of Hope, Duarte, CA, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.affiliation: Sylvester Comprehensive Cancer Center and Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Hu
authors.affiliation: Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, DC, USA.
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Nyante
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors.forename: Elisa V
authors.initials: EV
authors.lastname: Bandera
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: Sue A
authors.initials: SA
authors.lastname: Ingles
authors.affiliation: Department of Pathology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Press
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Nathanson
authors.affiliation: Chronic Disease Research Centre and Tropical Medicine Research Institute, University of the West Indies, Bridgetown, Barbados.
authors.forename: Anselm
authors.initials: A
authors.lastname: Hennis
authors.affiliation: Department of Preventive Medicine, State University of New York at Stony Brook, Stony Brook, NY, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Nemesure
authors.affiliation: Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ambs
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.affiliation: Department of Public Health Sciences, University of Chicago, 5841 S. Maryland Ave., MC 2007, Chicago, IL, 60637, USA. dhuo@health.bsd.uchicago.edu.
authors.forename: Dezheng
authors.initials: D
authors.lastname: Huo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044383:Black People; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043244:Ribonuclease III / Q000235:genetics*; D012307:Risk Factors
chemical_list: D004268:DNA-Binding Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D035683:MicroRNAs; C511130:TUT4 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III