title: Potentially functional variants in lncRNAs are associated with breast cancer risk in a Chinese population.
abstract: Long non-coding RNAs (lncRNAs) participate in the development of breast cancer. Genetic variants in lncRNAs may be involved in their abnormal expressions and associated with cancer risk. In the present study, we performed RNA sequencing on five paired breast cancer tumor and adjacent non-cancerous tissues to obtain differentially expressed lncRNAs. We systematically selected potential regulatory variants of these lncRNAs and investigated the associations between these variants and breast cancer susceptibility in 1486 breast cancer cases and 1519 cancer-free controls in a Chinese population. Eleven lncRNAs were significantly differentially expressed between breast cancer tumor and normal tissues (false discovery rate (FDR) ≤0.05 and fold-change ≥2), including two known lncRNAs HOTAIR and UCA1. We subsequently genotyped 20 variants located on these lncRNAs and identified two variants (rs11471161 in AC104135.3 and rs3751232 in RP11-1060J15.4) associated with breast cancer risk. Logistic regression analysis indicated that the variant allele of rs11471161 was significantly associated with a decreased breast cancer risk (additive model: OR = 0.84, 95%CI = 0.74-0.94, P = 0.004), while the variant allele of rs3751232 showed an increased risk of breast cancer (additive model: OR = 1.20, 95%CI = 1.02-1.40, P = 0.027). Further co-expression analysis indicated that AC104135.3 associated with ERBB2, which promotes the development and progression of breast cancer through overexpression. Together, these results suggest that genetic variants rs11471161 and rs3751232 in AC104135.3, and RP11-1060J15.4, respectively, may influence the susceptibility to breast cancer in the Chinese population. Further functional evaluations and larger studies are warranted to validate these findings.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.|Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Yue
authors.identifier: 0000-0002-7725-272X
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.|Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Fangzhi
authors.initials: F
authors.lastname: Du
authors.affiliation: Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.|Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.|Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.|Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.|Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.|Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Zhening
authors.initials: Z
authors.lastname: Pu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.|Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.|Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Jiaping
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.|Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.|Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.|Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Guangfu
authors.identifier: 0000-0003-0249-5337
authors.initials: G
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.|Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.|Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D044466:Asian People / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000235:genetics*; D012334:RNA, Neoplasm; D038621:Regulatory Sequences, Ribonucleic Acid; D012307:Risk Factors; D017423:Sequence Analysis, RNA
chemical_list: D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm; D038621:Regulatory Sequences, Ribonucleic Acid
keywords: breast cancer; genetic variants; lncRNAs; susceptibility