机构：[1]Shandong Univ, Hosp 2, Cheeloo Coll Med, Dept Breast Surg, Jinan, Peoples R China[2]Shandong Univ, Cheeloo Coll Med, Sch Med, Jinan, Peoples R China[3]Shandong Univ, Inst Translat Med Breast Dis Prevent & Treatment, Jinan, Peoples R China[4]Shandong Prov Engn Lab Translat Res Prevent & Tre, Jinan, Peoples R China[5]Zhengzhou Univ, Dept Breast Surg, Affiliated Tumor Hosp, Zhengzhou, Peoples R China河南省肿瘤医院[6]Shanxi Canc Hosp, Dept Breast Surg, Taiyuan, Peoples R China[7]First Hosp Jilin Univ, Dept Breast Surg, Changchun, Peoples R China[8]Hebei Med Univ, Dept Breast Ctr, Hosp 4, Shijiazhuang, Hebei, Peoples R China临床科室外一科河北医科大学第四医院[9]Tianjin Med Univ Canc Inst & Hosp, Dept Breast Surg, Tianjin, Peoples R China[10]Binzhou Med Univ, Dept Thyroid & Breast Surg, Affiliated Hosp 1, Binzhou, Peoples R China[11]Chinese Acad Med Sci, Canc Hosp, Dept Breast Surg, Beijing, Peoples R China[12]Linyi Peoples Hosp, Dept Gen Surg, Linyi, Shandong, Peoples R China[13]Peking Univ Peoples Hosp, Dept Breast Dis Ctr, Beijing, Peoples R China[14]Beijing Chaoyang Hosp, Dept Gen Surg, Beijing, Peoples R China北京朝阳医院[15]Peking Univ First Hosp, Dept Breast Dis Ctr, Beijing, Peoples R China[16]Qingdao Univ, Dept Breast Ctr, Affiliated Hosp, Qingdao, Peoples R China[17]Weifang Tradit Chinese Hosp, Dept Breast & Thyroid Surg, Weifang, Peoples R China[18]Qingdao Cent Hosp, Qingdao Med Coll, Dept Breast Surg, Affiliated Hosp 2, Qingdao, Peoples R China[19]Harbin Med Univ, Dept Gen Surg, Affiliated Hosp 2, Harbin, Peoples R China[20]China Med Univ, Dept Breast Surg, Affiliated Hosp 1, Shenyang, Peoples R China[21]Nanjing Med Univ, Canc Inst Jiangsu Prov, Dept Gen Surg, Affiliated Canc Hosp, Nanjing, Peoples R China[22]Zibo Cent Hosp, Dept Breast & Thyroid Surg, Zibo, Peoples R China[23]Yantai Yuhuangding Hosp, Dept Breast Surg, Yantai, Peoples R China[24]Shandong Canc Hosp, Dept Breast Canc Ctr, Jinan, Peoples R China
Background: Leptin (LEP) plays a physiological role through its specific receptor (LEPR) and is involved in the occurrence and development of breast cancer. Our current study aimed at determining the influence of single-nucleotide polymorphisms (SNPs) in the genes coding for LEP and LEPR on breast cancer risk. Methods: In the present study, 963 breast cancer cases and 953 controls were enrolled. Five SNPs of LEP and two of LEPR were chosen to evaluate the correlation of selected SNPs with breast cancer susceptibility among women in northern and eastern China. Analyses were further stratified by body mass index (EMI), waist-hip rate (VVHR), estrogen receptor, and progesterone receptor status. The expression patterns of risk variant- associated genes were detected by expression quantitative trait locus (eQTL) analysis with eQTLGen and The Cancer Genome Atlas database. Results: There were significant differences between breast cancer cases and control groups in the menopausal status and family history of breast cancer. Two SNPs (rs1137101 and rs4655555) of the LEPR gene decreased overall breast cancer risk, and other five SNPs showed no significant association with breast cancer risk. rs1137101 (GA vs. GG; adjusted OR = 0.719, 95% CI = 0.578-0.894, p = 0.003) and rs4655555 (TT vs. AA; adjusted OR = 0.574, 95% CI = 0.377-0.873, p = 0.009) significantly decreased breast cancer risk after Bonferroni correction for multiple testing. In subgroup analyses, the GA and GA + AA genotypes of LEPR rs1137101 associated with decreased breast cancer risk in the subgroup of BMI <= 24 kg/m(2) or WHR 0.85 after Bonferroni correction. Furthermore, we found that the expressions of rs4655555-associated gene LEPR and leptin receptor overlapping transcript (LEPROT) were upregulated in breast cancer tumor tissues compared with adjacent normal tissues, and a higher expression of LEPR in tumor tissues was correlated with poor prognosis of breast cancer patients using The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) data. Conclusion: Our study demonstrated that the polymorphisms rs1137101 and rs4655555 located in the LEPR gene decreased breast cancer risk in Chinese females, which might be a research-worthy bio-diagnostic marker and applied for early prediction and risk assessment of breast cancer.
基金：
National Natural Science Foundation of China [82072914]; Natural Science Foundation of Shandong Province [ZR2019PH016]; National Key Research and Development Program of China [2016YFC0901300]
第一作者机构：[1]Shandong Univ, Hosp 2, Cheeloo Coll Med, Dept Breast Surg, Jinan, Peoples R China[2]Shandong Univ, Cheeloo Coll Med, Sch Med, Jinan, Peoples R China[3]Shandong Univ, Inst Translat Med Breast Dis Prevent & Treatment, Jinan, Peoples R China[4]Shandong Prov Engn Lab Translat Res Prevent & Tre, Jinan, Peoples R China[22]Zibo Cent Hosp, Dept Breast & Thyroid Surg, Zibo, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Shandong Univ, Hosp 2, Cheeloo Coll Med, Dept Breast Surg, Jinan, Peoples R China[3]Shandong Univ, Inst Translat Med Breast Dis Prevent & Treatment, Jinan, Peoples R China[4]Shandong Prov Engn Lab Translat Res Prevent & Tre, Jinan, Peoples R China
推荐引用方式(GB/T 7714)：
Li Liang,Meng Xingchen,Liu Liyuan,et al.Single-Nucleotide Polymorphisms in LEP and LEPR Associated With Breast Cancer Risk: Results From a Multicenter Case-Control Study in Chinese Females[J].FRONTIERS IN ONCOLOGY.2021,12:doi:10.3389/fonc.2022.809570.
APA：
Li, Liang,Meng, Xingchen,Liu, Liyuan,Xiang, Yujuan,Wang, Fei...&Yu, Zhigang.(2021).Single-Nucleotide Polymorphisms in LEP and LEPR Associated With Breast Cancer Risk: Results From a Multicenter Case-Control Study in Chinese Females.FRONTIERS IN ONCOLOGY,12,
MLA：
Li, Liang,et al."Single-Nucleotide Polymorphisms in LEP and LEPR Associated With Breast Cancer Risk: Results From a Multicenter Case-Control Study in Chinese Females".FRONTIERS IN ONCOLOGY 12.(2021)
