Frontiers in Oncology (Feb 2022)
Single-Nucleotide Polymorphisms in LEP and LEPR Associated With Breast Cancer Risk: Results From a Multicenter Case–Control Study in Chinese Females
- Liang Li,
- Liang Li,
- Liang Li,
- Liang Li,
- Xingchen Meng,
- Xingchen Meng,
- Liyuan Liu,
- Liyuan Liu,
- Liyuan Liu,
- Yujuan Xiang,
- Yujuan Xiang,
- Yujuan Xiang,
- Fei Wang,
- Fei Wang,
- Fei Wang,
- Lixiang Yu,
- Lixiang Yu,
- Lixiang Yu,
- Fei Zhou,
- Fei Zhou,
- Fei Zhou,
- Chao Zheng,
- Chao Zheng,
- Chao Zheng,
- Wenzhong Zhou,
- Wenzhong Zhou,
- Wenzhong Zhou,
- Shude Cui,
- Fuguo Tian,
- Zhimin Fan,
- Cuizhi Geng,
- Xuchen Cao,
- Zhenlin Yang,
- Xiang Wang,
- Hong Liang,
- Shu Wang,
- Hongchuan Jiang,
- Xuening Duan,
- Haibo Wang,
- Guolou Li,
- Qitang Wang,
- Jianguo Zhang,
- Feng Jin,
- Jinhai Tang,
- Liang Li,
- Shiguang Zhu,
- Wenshu Zuo,
- Chunmiao Ye,
- Chunmiao Ye,
- Gengshen Yin,
- Gengshen Yin,
- Zhongbing Ma,
- Zhongbing Ma,
- Zhongbing Ma,
- Shuya Huang,
- Shuya Huang,
- Shuya Huang,
- Zhigang Yu,
- Zhigang Yu,
- Zhigang Yu
Affiliations
- Liang Li
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Liang Li
- School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Liang Li
- Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, China
- Liang Li
- Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease, Jinan, China
- Xingchen Meng
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Xingchen Meng
- School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Liyuan Liu
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Liyuan Liu
- Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, China
- Liyuan Liu
- Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease, Jinan, China
- Yujuan Xiang
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Yujuan Xiang
- Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, China
- Yujuan Xiang
- Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease, Jinan, China
- Fei Wang
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Fei Wang
- Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, China
- Fei Wang
- Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease, Jinan, China
- Lixiang Yu
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Lixiang Yu
- Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, China
- Lixiang Yu
- Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease, Jinan, China
- Fei Zhou
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Fei Zhou
- Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, China
- Fei Zhou
- Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease, Jinan, China
- Chao Zheng
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Chao Zheng
- Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, China
- Chao Zheng
- Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease, Jinan, China
- Wenzhong Zhou
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Wenzhong Zhou
- Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, China
- Wenzhong Zhou
- Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease, Jinan, China
- Shude Cui
- Department of Breast Surgery, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, China
- Fuguo Tian
- Department of Breast Surgery, Shanxi Cancer Hospital, Taiyuan, China
- Zhimin Fan
- Department of Breast Surgery, The First Hospital of Jilin University, Changchun, China
- Cuizhi Geng
- Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
- Xuchen Cao
- Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- Zhenlin Yang
- 0Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Binzhou Medical University, Binzhou, China
- Xiang Wang
- 1Department of Breast Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Hong Liang
- 2Department of General Surgery, Linyi People’s Hospital, Linyi, China
- Shu Wang
- 3Department of Breast Disease Center, Peking University People’s Hospital, Beijing, China
- Hongchuan Jiang
- 4Department of General Surgery, Beijing Chaoyang Hospital, Beijing, China
- Xuening Duan
- 5Department of Breast Disease Center, Peking University First Hospital, Beijing, China
- Haibo Wang
- 6Department of Breast Center, Qingdao University Affiliated Hospital, Qingdao, China
- Guolou Li
- 7Department of Breast and Thyroid Surgery, Weifang Traditional Chinese Hospital, Weifang, China
- Qitang Wang
- 8Department of Breast Surgery, The Second Affiliated Hospital of Qingdao Medical College, Qingdao Central Hospital, Qingdao, China
- Jianguo Zhang
- 9Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
- Feng Jin
- 0Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
- Jinhai Tang
- 1Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China
- Liang Li
- 2Department of Breast and Thyroid Surgery, Zibo Central Hospital, Zibo, China
- Shiguang Zhu
- 3Department of Breast Surgery, Yantai Yuhuangding Hospital, Yantai, China
- Wenshu Zuo
- 4Department of Breast Cancer Center, Shandong Cancer Hospital, Jinan, China
- Chunmiao Ye
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Chunmiao Ye
- School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Gengshen Yin
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Gengshen Yin
- School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Zhongbing Ma
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Zhongbing Ma
- Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, China
- Zhongbing Ma
- Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease, Jinan, China
- Shuya Huang
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shuya Huang
- Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, China
- Shuya Huang
- Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease, Jinan, China
- Zhigang Yu
- Department of Breast Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Zhigang Yu
- Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, China
- Zhigang Yu
- Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease, Jinan, China
- DOI
- https://doi.org/10.3389/fonc.2022.809570
- Journal volume & issue
-
Vol. 12
Abstract
BackgroundLeptin (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.MethodsIn 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 (BMI), waist–hip rate (WHR), 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.ResultsThere 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/m2 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.ConclusionOur 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.
Keywords
