This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Qu, S. Articles by Zheng, W. PubMed PubMed Citation Articles by Qu, S. Articles by Zheng, W.

Genetic Polymorphisms of Metastasis Suppressor Gene NME1 and Breast Cancer Survival

Authors' Affiliations: ¹ Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee and ² Department of Epidemiology, Shanghai Cancer Institute, Shanghai, People's Republic of China

Requests for reprints: Shimian Qu, Vanderbilt Epidemiology Center, Institute of Medicine and Public Health, Vanderbilt University School of Medicine, B2120 Medical Center North, 1161 21st Avenue South, Nashville, TN 37232. Phone: 615-936-5301; Fax: 615-322-1754; E-mail: Shimian.Qu{at}vanderbilt.edu.

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.