Limits...
Significance of rs1271572 in the estrogen receptor beta gene promoter and its correlation with breast cancer in a southwestern Chinese population.

Chen L, Liang Y, Qiu J, Zhang L, Chen X, Luo X, Jiang J - J. Biomed. Sci. (2013)

Bottom Line: The rs1271572 G→T SNP abrogated YY1 binding and reduced the transcription activity of the promoter 0 N in the ERβ gene in vitro.TT genotype of rs1271572 inhibited expression of ERβ gene by down regulating transcriptional activity of the promoter 0 N in the ERβ gene.Our data revealed that the TT genotype of rs1271572 resulted in loss of the YY1 binding site and reduced the transcription activity of the promoter 0 N in the ERβ gene.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: To characterize single nucleotide polymorphisms (SNPs) within the promoter region of the estrogen receptor beta (ERβ) gene and to analyze the association of ERβ SNPs with susceptibility to breast cancer. Genotype frequencies of five SNPs (rs3020449, rs3020450, rs2987983, rs1271572 and rs1887994) in the promoter region of the ERβ gene in 873 women with breast cancer, 645 women with fibroadenoma and 700 healthy women were determined using an allele-specific tetra-primer polymerase chain reaction (PCR). Kaplan-Meier survival analysis was performed to evaluate the association of selected rs1271572 with prognosis in breast cancer. Electrophoretic mobility-shift assays were conducted to explore the binding of SNP rs1271572 containing probes to transcriptional factor Ying Yang 1 (YY1).

Results: Women with the homozygous TT genotype of rs1271572 had a significantly higher risk in developing breast cancer. Breast cancer patients with the TT genotype of rs1271572 had lower five-year survival rates than those with other genotypes and were more likely to suffer brain metastases. The rs1271572 G→T SNP abrogated YY1 binding and reduced the transcription activity of the promoter 0 N in the ERβ gene in vitro.

Conclusions: TT genotype of rs1271572 is associated with increased risk for breast cancer in Chinese women and is associated with unfavored prognosis in Chinese breast cancer patients. TT genotype of rs1271572 inhibited expression of ERβ gene by down regulating transcriptional activity of the promoter 0 N in the ERβ gene. Our data revealed that the TT genotype of rs1271572 resulted in loss of the YY1 binding site and reduced the transcription activity of the promoter 0 N in the ERβ gene.

Show MeSH

Related in: MedlinePlus

TT genotype of rs1271572 was associated with worse survival in breast cancer. Kaplan–Meier breast cancer-free survival was applied to determine the prognosis A) among patients with the three genotypes (GG, GT and TT) of rs1271572; B) between ERβ–positive and ERβ–negative patients; C) between ERβ–negative and ERβ–positive patients in the ER- subgroup, and D) between ERβ–negative and ERβ–positive patients in the Her + patients. The p values were determined using the log-rank test; a significant difference was assumed for p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3672062&req=5

Figure 3: TT genotype of rs1271572 was associated with worse survival in breast cancer. Kaplan–Meier breast cancer-free survival was applied to determine the prognosis A) among patients with the three genotypes (GG, GT and TT) of rs1271572; B) between ERβ–positive and ERβ–negative patients; C) between ERβ–negative and ERβ–positive patients in the ER- subgroup, and D) between ERβ–negative and ERβ–positive patients in the Her + patients. The p values were determined using the log-rank test; a significant difference was assumed for p < 0.05.

Mentions: The median follow up period was 43.24 (range 8.2–62.46) months for the participated cancer patients, and the mean follow up period was 49.33 months. The Kaplan-Meier survival analyses demonstrated that patients with the TT genotype of rs1271572 had a shorter survival rate than patients with the GG or GT genotypes of rs1271572 (p < 0.001, Figure 3A). No significant difference in survival rates between ERβ–positive and ERβ–negative patients (p = 0.055, Figure 3B) was observed. However, among ERα–negative and Her2-positive cases, ERβ–negative patients had a shorter survival rate than ERβ–positive patients (p = 0.015 and p < 0.001, respectively) (Figure 3C and3D). However, among ERα–positive and Her2-negative cases, no correlations were observed between the expression levels of ERβ and survival rates (data not shown). In addition, we found that breast cancer patients with the TT genotype of rs1271572 were more likely to suffer brain metastases (29.23%) than patients with the GG (10.34%) or GT (9.47%) genotypes (p = 0.005) (Table 4). The location of distant metastases was recorded for the first metastatic organ found during the follow-up period. Data for patients with multiple organ metastasis first diagnosed during follow-up, were grouped in “other” in Table 4.


Significance of rs1271572 in the estrogen receptor beta gene promoter and its correlation with breast cancer in a southwestern Chinese population.

Chen L, Liang Y, Qiu J, Zhang L, Chen X, Luo X, Jiang J - J. Biomed. Sci. (2013)

TT genotype of rs1271572 was associated with worse survival in breast cancer. Kaplan–Meier breast cancer-free survival was applied to determine the prognosis A) among patients with the three genotypes (GG, GT and TT) of rs1271572; B) between ERβ–positive and ERβ–negative patients; C) between ERβ–negative and ERβ–positive patients in the ER- subgroup, and D) between ERβ–negative and ERβ–positive patients in the Her + patients. The p values were determined using the log-rank test; a significant difference was assumed for p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672062&req=5

Figure 3: TT genotype of rs1271572 was associated with worse survival in breast cancer. Kaplan–Meier breast cancer-free survival was applied to determine the prognosis A) among patients with the three genotypes (GG, GT and TT) of rs1271572; B) between ERβ–positive and ERβ–negative patients; C) between ERβ–negative and ERβ–positive patients in the ER- subgroup, and D) between ERβ–negative and ERβ–positive patients in the Her + patients. The p values were determined using the log-rank test; a significant difference was assumed for p < 0.05.
Mentions: The median follow up period was 43.24 (range 8.2–62.46) months for the participated cancer patients, and the mean follow up period was 49.33 months. The Kaplan-Meier survival analyses demonstrated that patients with the TT genotype of rs1271572 had a shorter survival rate than patients with the GG or GT genotypes of rs1271572 (p < 0.001, Figure 3A). No significant difference in survival rates between ERβ–positive and ERβ–negative patients (p = 0.055, Figure 3B) was observed. However, among ERα–negative and Her2-positive cases, ERβ–negative patients had a shorter survival rate than ERβ–positive patients (p = 0.015 and p < 0.001, respectively) (Figure 3C and3D). However, among ERα–positive and Her2-negative cases, no correlations were observed between the expression levels of ERβ and survival rates (data not shown). In addition, we found that breast cancer patients with the TT genotype of rs1271572 were more likely to suffer brain metastases (29.23%) than patients with the GG (10.34%) or GT (9.47%) genotypes (p = 0.005) (Table 4). The location of distant metastases was recorded for the first metastatic organ found during the follow-up period. Data for patients with multiple organ metastasis first diagnosed during follow-up, were grouped in “other” in Table 4.

Bottom Line: The rs1271572 G→T SNP abrogated YY1 binding and reduced the transcription activity of the promoter 0 N in the ERβ gene in vitro.TT genotype of rs1271572 inhibited expression of ERβ gene by down regulating transcriptional activity of the promoter 0 N in the ERβ gene.Our data revealed that the TT genotype of rs1271572 resulted in loss of the YY1 binding site and reduced the transcription activity of the promoter 0 N in the ERβ gene.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: To characterize single nucleotide polymorphisms (SNPs) within the promoter region of the estrogen receptor beta (ERβ) gene and to analyze the association of ERβ SNPs with susceptibility to breast cancer. Genotype frequencies of five SNPs (rs3020449, rs3020450, rs2987983, rs1271572 and rs1887994) in the promoter region of the ERβ gene in 873 women with breast cancer, 645 women with fibroadenoma and 700 healthy women were determined using an allele-specific tetra-primer polymerase chain reaction (PCR). Kaplan-Meier survival analysis was performed to evaluate the association of selected rs1271572 with prognosis in breast cancer. Electrophoretic mobility-shift assays were conducted to explore the binding of SNP rs1271572 containing probes to transcriptional factor Ying Yang 1 (YY1).

Results: Women with the homozygous TT genotype of rs1271572 had a significantly higher risk in developing breast cancer. Breast cancer patients with the TT genotype of rs1271572 had lower five-year survival rates than those with other genotypes and were more likely to suffer brain metastases. The rs1271572 G→T SNP abrogated YY1 binding and reduced the transcription activity of the promoter 0 N in the ERβ gene in vitro.

Conclusions: TT genotype of rs1271572 is associated with increased risk for breast cancer in Chinese women and is associated with unfavored prognosis in Chinese breast cancer patients. TT genotype of rs1271572 inhibited expression of ERβ gene by down regulating transcriptional activity of the promoter 0 N in the ERβ gene. Our data revealed that the TT genotype of rs1271572 resulted in loss of the YY1 binding site and reduced the transcription activity of the promoter 0 N in the ERβ gene.

Show MeSH
Related in: MedlinePlus