These results indicate that PON1L55M genetic polymorphisms may be associated with the risk of breast cancer and could potentially serve as useful genetic markers for tumor prognosis in some populations of Chinese women.
The aims of our study were to investigate the changes produced by radiotherapy (RT) on activity and concentration of serum PON1 in BC patients, and to evaluate the observed variations in relation to clinical and pathological characteristics of patients and tumors, and the response to treatment.
In this context, structural defects of typical genes related to both BC and obesity, such as leptin, leptin receptor, serum paraoxonase/arylesterase 1, the fat mass and obesity-associated gene and melanocortin receptor 4, have been associated with a high or low risk of BC development.
Here, we report that upregulation of hyaluronan synthase 2 (HAS2) occurs in highly metastatic breast cancer stem-like cells (CSC) defined by CD44(+)/CD24(-)/ESA(+) phenotype, where it plays a critical role in the generation of a prometastatic microenvironment in breast cancer.
We therefore carried out a meta-analysis of published studies to clarify this inconsistency and to establish a comprehensive picture of the relationship between PON1 gene variants and breast cancer risk.
Inhibition of the HR pathway effectively sterilised the CD24(- ) ESA(+) sorted MDA-MB231 cells but had no effect on the unsorted cells or MDA468 control breast cancer cell line.
However, as regard PON1Q192R, the R mutated allele frequency was found in 28.5% in BC patients and in 33% in controls, the women who were QR heterozygotes (OR(adj) 0.96, 95% CI 0.55-1.68) or RR homozygotes (OR(adj) 0.64, 95% CI 0.25-1.63), and R allele (OR(adj) 0.81, 95% CI 0.53-1.42) did not show any risk for BC.
The present meta-analysis suggested that LEPR Q223R polymorphism might be implicated in the development of breast cancer in East Asians; PON1L55M might increase breast cancer risk.
As to GSTP1 and PON1 192 polymorphisms, the mutant Val and R alleles, respectively, were associated with a decreased risk of developing BC, while polymorphisms in PON1 55 and GLO1 were associated with an increased risk of this neoplasia.
The findings suggest that specific polymorphisms in the PON1 and LEPR genes may play a role in progression of BBD to breast cancer among post-menopausal Caucasian women.
These results suggest that genetic variation in PON1, particularly at the L55M SNP, may be associated with increased risk of breast cancer in postmenopausal women.