Genetic polymorphisms of metastasis suppressor gene NME1 and breast cancer survival.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
Promoter polymorphisms in the NME1 gene may alter its expression and influence breast cancer survival.
Qu
Shimian
S
Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. Shimian.Qu@vanderbilt.edu
Long
Jirong
J
Cai
Qiuyin
Q
Shu
Xiao-Ou
XO
Cai
Hui
H
Gao
Yu-Tang
YT
Zheng
Wei
W
D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D054778:NM23 Nucleoside Diphosphate Kinases / Q000096:biosynthesis* / Q000235:genetics*; D009362:Neoplasm Metastasis; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D016896:Treatment Outcome
D054778:NM23 Nucleoside Diphosphate Kinases; C517938:NME1 protein, human