Shuya Huang1,2, Liyuan Liu1,2, Yujuan Xiang1,2, Fei Wang1,2, Lixiang Yu1,2, Fei Zhou1,2, Shude Cui3, Fuguo Tian4, Zhimin Fan5, Cuizhi Geng6, Xuchen Cao7, Zhenlin Yang8, Xiang Wang9, Hong Liang10, Shu Wang11, Hongchuan Jiang12, Xuening Duan13, Haibo Wang14, Guolou Li15, Qitang Wang16, Jianguo Zhang17, Feng Jin18, Jinhai Tang19, Liang Li20, Shiguang Zhu21, Wenshu Zuo22, Chunmiao Ye1, Wenzhong Zhou1, Gengshen Yin1, Zhongbing Ma1,2, Zhigang Yu1,2. 1. Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong, People's Republic of China. 2. Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong, People's Republic of China. 3. Department of Breast Surgery, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China. 4. Department of Breast Surgery, Shanxi Cancer Hospital, Taiyuan, Shanxi, People's Republic of China. 5. Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China. 6. Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China. 7. Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China. 8. Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, People's Republic of China. 9. Department of Breast Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China. 10. Department of General Surgery, Linyi People's Hospital, Linyi, Shandong, People's Republic of China. 11. Department of Breast Disease Center, Peking University People's Hospital, Beijing, People's Republic of China. 12. Department of General Surgery, Beijing Chaoyang Hospital, Beijing, People's Republic of China. 13. Department of Breast Disease Center, Peking University First Hospital, Beijing, People's Republic of China. 14. Department of Breast Center, Qingdao University Affiliated Hospital, Qingdao, Shandong, People's Republic of China. 15. Department of Breast and Thyroid Surgery, Weifang Traditional Chinese Hospital, Weifang, Shandong, People's Republic of China. 16. Department of Breast Surgery, The Second Affiliated Hospital of Qingdao Medical College, Qingdao Central Hospital, Qingdao, Shandong, People's Republic of China. 17. Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China. 18. Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China. 19. Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, People's Republic of China. 20. Department of Breast and Thyroid Surgery, Zibo Central Hospital, Zibo, Shandong, People's Republic of China. 21. Department of Breast Surgery, Yantai Yuhuangding Hospital, Yantai, Shandong, People's Republic of China. 22. Department of Breast Cancer Center, Shandong Cancer Hospital, Jinan, Shandong, People's Republic of China.
Abstract
BACKGROUND: Breast cancer (BC) risk, development, and prognosis were closely related to obesity, diabetes mellitus, and metabolic syndrome. Protein tyrosine phosphatase, non-receptor type 1 (PTPN1) located on chromosome 20q13, could negatively regulate insulin and leptin signaling. In this study, we determined the association of PTPN1 polymorphisms with BC risk. METHODS: We analyzed the distribution of 11 selected PTPN1 single nucleotide polymorphisms in Chinese female patients with BC (n = 953) and healthy controls (n = 963) based on a multicenter case-control study. The association of PTPN1 genotypes and haplotypes frequencies with BC risk were determined by logistic regression analysis. Analyses were further stratified by body mass index (BMI), waist-hip rate (WHR), diabetes mellitus history, and fasting plasma glucose level. The eQTL (expression Quantitative Trait Loci) analysis for PTPN1 was conducted by GTEx database. RESULTS: There were significant differences between BC cases and control groups in menopausal status, number of births, and BMI. Four single nucleotide polymorphisms (SNPs; rs3215684, rs3787345, rs718049, and rs718050) decreased overall BC risk, and other seven SNPs showed no significant association with BC risk. In multivariate analysis, BMI and rs3215684 DT + DD genotype were identified as independent risk factors for BC, and mutated genotypes of rs3215684 were correlated with increased PTPN1 expression. There are no haplotypes showed different frequencies between cases and controls. In the stratified analysis, rs2206656 showed a significant association with decreased BC risk in the subgroup of BMI ≤ 24 kg/m 2 , while rs3215684 and rs718049 showed lower BC risk in the subgroup of WHR > 0.85. Seven SNPs showed lower BC risk in the subgroup with diabetes mellitus history and/or fasting plasma glucose level ≥ 7 mM, while rs754118 decreased BC risk in the subgroup of fasting plasma glucose level < 7 mM. CONCLUSION: Our findings suggest that PTPN1 SNPs associated with BC susceptibility in Chinese females, which also suggested a novel mechanism between obesity, diabetes mellitus, and BC risk.
BACKGROUND:Breast cancer (BC) risk, development, and prognosis were closely related to obesity, diabetes mellitus, and metabolic syndrome. Protein tyrosine phosphatase, non-receptor type 1 (PTPN1) located on chromosome 20q13, could negatively regulate insulin and leptin signaling. In this study, we determined the association of PTPN1 polymorphisms with BC risk. METHODS: We analyzed the distribution of 11 selected PTPN1 single nucleotide polymorphisms in Chinese female patients with BC (n = 953) and healthy controls (n = 963) based on a multicenter case-control study. The association of PTPN1 genotypes and haplotypes frequencies with BC risk were determined by logistic regression analysis. Analyses were further stratified by body mass index (BMI), waist-hip rate (WHR), diabetes mellitus history, and fasting plasma glucose level. The eQTL (expression Quantitative Trait Loci) analysis for PTPN1 was conducted by GTEx database. RESULTS: There were significant differences between BC cases and control groups in menopausal status, number of births, and BMI. Four single nucleotide polymorphisms (SNPs; rs3215684, rs3787345, rs718049, and rs718050) decreased overall BC risk, and other seven SNPs showed no significant association with BC risk. In multivariate analysis, BMI and rs3215684 DT + DD genotype were identified as independent risk factors for BC, and mutated genotypes of rs3215684 were correlated with increased PTPN1 expression. There are no haplotypes showed different frequencies between cases and controls. In the stratified analysis, rs2206656 showed a significant association with decreased BC risk in the subgroup of BMI ≤ 24 kg/m 2 , while rs3215684 and rs718049 showed lower BC risk in the subgroup of WHR > 0.85. Seven SNPs showed lower BC risk in the subgroup with diabetes mellitus history and/or fasting plasma glucose level ≥ 7 mM, while rs754118 decreased BC risk in the subgroup of fasting plasma glucose level < 7 mM. CONCLUSION: Our findings suggest that PTPN1 SNPs associated with BC susceptibility in Chinese females, which also suggested a novel mechanism between obesity, diabetes mellitus, and BC risk.