Diverse associations between ESR1 polymorphism and breast cancer development and progression.
OBJECTIVE
To test the hypothesis that polymorphisms of ESR1, the gene encoding estrogen receptor alpha (ERalpha), are associated with susceptibility, clinical phenotype, and progression of breast cancer.


METHODS
A case-control study was done on 940 patients with incident breast cancer and 1,547 healthy female controls. Fifteen single-nucleotide polymorphisms (SNP) selected from chr6:152,170,379-152,466,100 (exons 1-8 of the ESR1 gene, excluding flanking sequences), reflecting major polymorphisms of this gene, were genotyped. Frequencies of SNPs were compared between cases and controls to identify SNPs associated with cancer susceptibility and between cases with different clinical phenotypes to determine the role of ESR1 polymorphism in cancer progression.


RESULTS
SNPs located in one cluster in intron 1 and one haplotype, based on these SNPs, showed a significant association with breast cancer susceptibility. The tumorigenic contribution of these intron 1 SNPs was more obvious in combination with reproductive risk factors (P for interaction <0.05). One of these intron 1 SNPs was also significantly associated with low ERalpha expression in tumors. Interestingly, the same intron 1 SNPs showed a correlation with worse clinical phenotypes, including poor differentiation of tumor cells and a late stage. These intron 1 SNPs also showed a significant association with the 5-year breast cancer-specific survival rate of patients, but had opposite effects in ERalpha-negative and ERalpha-positive early-stage patients.


CONCLUSIONS
Our findings provide support for diverse roles of ESR1 polymorphism in determining susceptibility in different stages of breast cancer. The differences between the important ESR1 SNPs identified in Chinese women in this study and those identified in studies on Western women with breast cancer suggest different roles of ERalpha in these two populations.
Ding
Shian-ling
SL
Department of Nursing, Kang-Ning Junior College of Medical Care and Management, Taipei, Taiwan. slding@knjc.edu.tw
Yu
Jyh-Cherng
JC
Chen
Shou-Tung
ST
Hsu
Giu-Cheng
GC
Hsu
Huan-Ming
HM
Ho
Jar Yi
JY
Lin
Yu Hsin
YH
Chang
Chien-Ching
CC
Fann
Cathy S J
CS
Cheng
Chun-Wen
CW
Wu
Pei-Ei
PE
Shen
Chen-Yang
CY
D044466:Asian People; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D018450:Disease Progression; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha