rs15869 at miRNA binding site in BRCA2 is associated with breast cancer susceptibility.
BRCA1 and BRCA2 mutations confer an increased lifetime risk of breast cancer; however, the associations of microRNA (miRNA) binding site single nucleotide polymorphisms (SNPs) in 3' untranslated region (3'-UTR) of BRCA1 and BRCA2 with breast cancer (BC) risk were rarely reported. In this case-control study (498 BC patients and 498 matched controls), three SNPs (rs8176318, rs12516 and rs15869) were selected in the 3'-UTR of BRCA1 and BRCA2 genes, which were within miRNA-binding seed regions and might have potential function to regulate the expression of BRCA1/BRCA2. Unconditional logistic regression model was used to analyze the association between three SNPs and BC risk with adjustment of reproductive factors, and Student's t test was performed to assess relative expression of BRCA2 in human breast cancer cell lines. Multifactor dimensionality reduction method was applied to calculate gene-reproductive factors interactions. A novel finding showed that AC [odds ratio (OR) 1.524; 95% confidence interval (CI) 1.141-2.035] genotype of rs15869 in BRCA2 could increase the risk of BC and recombinant plasmid-pGenesil-1-miR-627 could negatively regulate the expression of BRCA2 in MCF-7 and MDA-MB-231 cells. Gene-reproductive factors interactions analysis revealed that rs15869 together with age at menarche and number of pregnancy could increase the risk of BC by 2.39-fold and TT genotype (OR 0.316; 95% CI 0.130-0.767) of rs8176318 had a significant association with progesterone receptor status in BC patients. Our findings suggest that the miRNA-binding SNPs in BRCA1/BRCA2 and their interaction with reproductive factors might contribute to BC risk, and miR-627 might down-regulate BRCA2 expression in MCF-7 and MDA-MB-231 cells.
Department of Epidemiology and Statistics, College of Public health, Zhengzhou University, Zhengzhou, 450001, Henan Province, People's Republic of China.
Jingjing
J
Cao
Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, 79968, USA.
Chenglin
C
Luo
Department of Epidemiology and Statistics, College of Public health, Zhengzhou University, Zhengzhou, 450001, Henan Province, People's Republic of China.
Rui
R
Yan
Department of Epidemiology and Statistics, College of Public health, Zhengzhou University, Zhengzhou, 450001, Henan Province, People's Republic of China.
Rui
R
Peng
Department of Epidemiology and Statistics, College of Public health, Zhengzhou University, Zhengzhou, 450001, Henan Province, People's Republic of China.|Henan Key Laboratory of Tumor Epidemiology, Zhengzhou, 450001, Henan, People's Republic of China.
Kaijuan
K
Wang
Department of Epidemiology and Statistics, College of Public health, Zhengzhou University, Zhengzhou, 450001, Henan Province, People's Republic of China.|Henan Key Laboratory of Tumor Epidemiology, Zhengzhou, 450001, Henan, People's Republic of China.
Peng
P
Wang
Department of Epidemiology and Statistics, College of Public health, Zhengzhou University, Zhengzhou, 450001, Henan Province, People's Republic of China.|Henan Key Laboratory of Tumor Epidemiology, Zhengzhou, 450001, Henan, People's Republic of China.
Hua
H
Ye
Department of Epidemiology and Statistics, College of Public health, Zhengzhou University, Zhengzhou, 450001, Henan Province, People's Republic of China. sch16@zzu.edu.cn.|Henan Key Laboratory of Tumor Epidemiology, Zhengzhou, 450001, Henan, People's Republic of China. sch16@zzu.edu.cn.
Chunhua
C
Song
D020413:3' Untranslated Regions; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001665:Binding Sites; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D020413:3' Untranslated Regions; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004273:DNA, Neoplasm; C583638:MIRN627 microRNA, human; D035683:MicroRNAs
BRCA; Breast cancer; Genetic susceptibility; Interaction; miRNA binding site; miRNA-627