Shimian Qu1, Jirong Long, Qiuyin Cai, Xiao-Ou Shu, Hui Cai, Yu-Tang Gao, Wei Zheng. 1. Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. Shimian.Qu@vanderbilt.edu
Abstract
PURPOSE: Ample evidence supports an important role of tumor metastasis suppressor genes in cancer metastatic processes. We evaluated the association of genetic polymorphisms of metastasis suppressor gene NME1 with breast cancer prognosis in a follow-up study of patients with primary breast cancer and further investigated the functions of these polymorphisms. EXPERIMENTAL DESIGN: NME1 genotypes were analyzed in a cohort of 1,134 breast cancer patients recruited as part of the Shanghai Breast Cancer Study who were followed for a median of 7.1 years. In vitro biochemical analyses were carried out to examine the function of NME1 gene polymorphisms. RESULTS: Single nucleotide polymorphisms (SNP) in the promoter region of the NME1 gene were found to be associated with breast cancer prognosis. Patients carrying the C allele in rs16949649 were associated with higher breast cancer-specific mortality [hazard ratio (HR), 1.4; 95% confidence interval (95% CI), 1.1-1.9] compared with those carrying the wild-type allele, and the association was more evident in patients with an early-stage cancer (HR, 1.7; 95% CI, 1.2-2.5). SNP rs2302254 was also associated with breast cancer prognosis, and the association was statistically significant for the risk of breast cancer relapse, metastasis, and death (HR, 1.3; 95% CI, 1.0-1.6). In vitro biochemical analyses showed that minor alleles in rs2302254 and rs3760468, which is in strong linkage disequilibrium with rs16949646, altered nuclear proteins binding capacity and reduced NME1 promoter activity, supporting the results from an association study of these SNPs with breast cancer survival. CONCLUSION: Promoter polymorphisms in the NME1 gene may alter its expression and influence breast cancer survival.
PURPOSE: Ample evidence supports an important role of tumor metastasis suppressor genes in cancer metastatic processes. We evaluated the association of genetic polymorphisms of metastasis suppressor gene NME1 with breast cancer prognosis in a follow-up study of patients with primary breast cancer and further investigated the functions of these polymorphisms. EXPERIMENTAL DESIGN:NME1 genotypes were analyzed in a cohort of 1,134 breast cancerpatients recruited as part of the Shanghai Breast Cancer Study who were followed for a median of 7.1 years. In vitro biochemical analyses were carried out to examine the function of NME1 gene polymorphisms. RESULTS: Single nucleotide polymorphisms (SNP) in the promoter region of the NME1 gene were found to be associated with breast cancer prognosis. Patients carrying the C allele in rs16949649 were associated with higher breast cancer-specific mortality [hazard ratio (HR), 1.4; 95% confidence interval (95% CI), 1.1-1.9] compared with those carrying the wild-type allele, and the association was more evident in patients with an early-stage cancer (HR, 1.7; 95% CI, 1.2-2.5). SNP rs2302254 was also associated with breast cancer prognosis, and the association was statistically significant for the risk of breast cancer relapse, metastasis, and death (HR, 1.3; 95% CI, 1.0-1.6). In vitro biochemical analyses showed that minor alleles in rs2302254 and rs3760468, which is in strong linkage disequilibrium with rs16949646, altered nuclear proteins binding capacity and reduced NME1 promoter activity, supporting the results from an association study of these SNPs with breast cancer survival. CONCLUSION: Promoter polymorphisms in the NME1 gene may alter its expression and influence breast cancer survival.
Authors: Christine E Horak; Jong Heun Lee; Abdel G Elkahloun; Mathieu Boissan; Sylvie Dumont; Tara K Maga; Sandrine Arnaud-Dabernat; Diane Palmieri; William G Stetler-Stevenson; Marie-Lise Lacombe; Paul S Meltzer; Patricia S Steeg Journal: Cancer Res Date: 2007-08-01 Impact factor: 12.701
Authors: Taoufik Ouatas; Susan E Clare; Melanie T Hartsough; Abel De La Rosa; Patricia S Steeg Journal: Clin Exp Metastasis Date: 2002 Impact factor: 5.150
Authors: P S Steeg; G Bevilacqua; L Kopper; U P Thorgeirsson; J E Talmadge; L A Liotta; M E Sobel Journal: J Natl Cancer Inst Date: 1988-04-06 Impact factor: 13.506
Authors: Y T Gao; X O Shu; Q Dai; J D Potter; L A Brinton; W Wen; T A Sellers; L H Kushi; Z Ruan; R M Bostick; F Jin; W Zheng Journal: Int J Cancer Date: 2000-07-15 Impact factor: 7.396
Authors: Michelle R Roberts; Lara E Sucheston-Campbell; Gary R Zirpoli; Michael Higgins; Jo L Freudenheim; Elisa V Bandera; Christine B Ambrosone; Song Yao Journal: Mol Carcinog Date: 2016-09-21 Impact factor: 4.784
Authors: Ying Gao; Nan Hu; XiaoYou Han; Carol Giffen; Ti Ding; Alisa Goldstein; Philip Taylor Journal: BMC Cancer Date: 2009-08-05 Impact factor: 4.430