Dataset Information

The role of Prolactin/Prolactin Receptor polymorphisms and expression in breast cancer susceptibility and outcome

ABSTRACT:

Background

Prolactin (PRL) is a polypeptide hormone secreted by the anterior pituitary to stimulate growth and differentiation of the normal mammary gland. Together with its receptor, prolactin receptor (PRLR) have been shown to play a role in breast cancer. This study aimed to examine the roles of PRL and PRLR polymorphisms and expression in breast cancer risk and aggressiveness in Thai patients.

Methods

PRL (rs3756824 C/G and rs2244502 T/A) and PRLR (rs37364 G/T and rs249537 A/G) polymorphisms were genotyped by real-time PCR and PRLR expression was assessed by immunohistochemistry (IHC) in breast cancer tissues. The correlations between PRL and PRLR polymorphisms and breast cancer susceptibility/aggressiveness as well as the associations between PRLR expression and clinicopathological parameters were determined.

Results

Two hundred and twenty-seven breast cancer patients and 119 matched controls were recruited at the Division of Head Neck and Breast Surgery, Department of Surgery, Faculty of Medicine, Siriraj Hospital, Thailand from 2010–2014. PRL and PRLR polymorphisms were not correlated with breast cancer susceptibility and there was no association between PRLR polymorphisms and PRLR expression. PRLR was frequently overexpressed in breast cancer with positive hormone receptors. High expression of PRLR was significantly related to the presence of axillary nodal metastasis and lymphovascular invasion and showed a trend towards poorer outcome.

Conclusions

There was a correlation between high PRLR expression and aggressive features of breast cancer. PRLR expression might be utilized as a prognostic factor for identification of luminal breast cancer with poorer outcome.

SUBMITTER: Sa-nguanraksa D

PROVIDER: S-EPMC8798722 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundHigher circulating prolactin has been associated with increased breast cancer risk. Prolactin binding to the prolactin receptor (PRLR) can activate the transcription factor STAT5, thus, we examined the association between plasma prolactin and breast cancer risk by tumor expression of PRLR, STAT5, and the upstream kinase JAK2.MethodsUsing data from 745 cases and 2454 matched controls in the Nurses' Health Study, we conducted polytomous logistic regression to examine the association between prolactin (> 11 ng/mL vs. ≤ 11 ng/mL) measured within 10 years of diagnosis and breast cancer risk by PRLR (nuclear [N], cytoplasmic [C]), phosphorylated STAT5 (pSTAT5; N, C), and phosphorylated JAK2 (pJAK2; C) tumor expression. Analyses were conducted separately in premenopausal (n = 168 cases, 765 controls) and postmenopausal women (n = 577 cases, 1689 controls).ResultsIn premenopausal women, prolactin levels > 11 ng/mL were positively associated with risk of tumors positive for pSTAT5-N (OR 2.30, 95% CI 1.02-5.22) and pSTAT5-C (OR 1.64, 95% CI 1.01-2.65), but not tumors that were negative for these markers (OR 0.98, 95% CI 0.65-1.46 and OR 0.73, 95% CI 0.43-1.25; p-heterogeneity = 0.06 and 0.02, respectively). This was stronger when tumors were positive for both pSTAT5-N and pSTAT5-C (OR 2.88, 95% CI 1.14-7.25). No association was observed for PRLR or pJAK2 (positive or negative) and breast cancer risk among premenopausal women. Among postmenopausal women, plasma prolactin levels were positively associated with breast cancer risk irrespective of PRLR, pSTAT5, or pJAK2 expression (all p-heterogeneity ≥ 0.21).ConclusionWe did not observe clear differences in the association between plasma prolactin and breast cancer risk by tumor expression of PRLR or pJAK2, although associations for premenopausal women were observed for pSTAT5 positive tumors only. While additional studies are needed, this suggests that prolactin may act on human breast tumor development through alternative pathways.

Project description:Background:Inflammation is a fundamental factor that contributes to the development and progression of several types of cancer including colon cancer. Toll-like receptors (TLRs) and their signaling pathways have been reported to be associated with chronic inflammation and thereby induced cancer. Our aim was to investigate the expression and polymorphisms of TLR2 and their association with colon cancer. Methods:Real-time PCR and immunohistochemistry were used to investigate TLR2 gene expression and to evaluate the potential risk of predisposition to colon cancer caused by three tagging single-nucleotide polymorphisms (SNPs) on TLR2, including rs3804100, rs4696480, and rs3804099. TaqMan assay was conducted on samples from 115 patients with colon cancer and 102 age- and sex-matched normal individuals. Results:We found that, TLR2 was highly expressed in epithelial colon cancer cells and both TLR2 mRNA and protein levels, and significantly decreased in tumor tissues compared to normal tissues. Two of three TLR2 SNPs increased the risk of colon cancer. However, TLR2 rs3804099 increased the risk of colon cancer development by more than 3.8- and 5-fold in female patients and patients aged less than 57 years, respectively. The T allele of TLR2 rs3804100 showed a significant association with patients less than 57 years. In silico analysis of the TLR2 nucleotide substitution in SNP rs3804100 and rs3804099 determined that 67% and 70% probability of these single nucleotide variants alter splicing phenotypes, rs3804100 more specifically result on activating an additional splice site. Genotype and allele frequencies of rs4696480 were similar between the overall study populations. Thus, TLR2 rs4696480 appear to be not involved in colon cancer in our study population. Conclusions:There was a significant link between innate immunity deregulation through disruption of the TLRs and potential development of colon cancer. These SNPs can be used as screening markers for predicting colon cancer risk earlier in life to implement necessary prevention.