title: Genetic variation in a hsa-let-7 binding site in RAD52 is associated with breast cancer susceptibility.
abstract: Genetic variants may influence miRNA-mRNA interaction through modulate binding affinity, creating or destroying miRNA-binding sites. Twenty-four single nucleotide polymorphisms (SNPs) that were predicted to affect the binding affinity of breast cancer-related miRNAs to 3'-untranslated regions (UTR) of known genes were genotyped in 878 breast cancer cases and 900 controls in Chinese women. Three promising SNPs (rs10494836, rs10857748 and rs7963551) were further validated in additional 914 breast cancer cases and 967 controls. The variant allele (C) of rs7963551 at 3'-UTR of RAD52 showed a consistently reduced breast cancer risk in two stages with a combined odds ratio (OR) of 0.84 [95% confidence interval (CI) = 0.75-0.95], which was more prominent among women with early age at first live birth (OR = 0.71, 95% CI = 0.58-0.87). A significant interaction was observed between rs7963551 and age at first live birth on breast cancer risk (P for interaction = 0.04). Luciferase activity assay showed a higher expression level for rs7963551 C allele as compared with A allele (P = 5.19 × 10(-3) for MCF-7 cell lines), which might be due to a reduced inhibition from a weakened binding capacity of miRNA to 3'-UTR of RAD52 harboring C allele. These findings indicate that rs7963551 located at hsa-let-7 binding site may alter expression of RAD52 through modulating miRNA-mRNA interaction and contribute to the development of breast cancer in Chinese women.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University,  Nanjing 210029,  China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Qin
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Guan
authors.forename: Yanru
authors.initials: Y
authors.lastname: Wang
authors.forename: Yisha
authors.initials: Y
authors.lastname: He
authors.forename: Jialei
authors.initials: J
authors.lastname: Xue
authors.forename: Xiao'an
authors.initials: X
authors.lastname: Liu
authors.forename: Jiaping
authors.initials: J
authors.lastname: Chen
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.forename: Shui
authors.initials: S
authors.lastname: Wang
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002460:Cell Line; D002681:China; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D034622:RNA Interference; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics* / Q000378:metabolism; D012306:Risk
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C497194:RAD52 protein, human; D051721:Rad52 DNA Repair and Recombination Protein; C487931:mirnlet7 microRNA, human