ABSTRACT
GATA3 is an enriched transcription factor in mammary epithelium. To date, there has been no study on the relationship between microsatellites in the GATA3 gene and breast cancer risk. In this study, we investigated the existence of polymorphisms in the cytosine-thymine (CT) dinucleotide repeat in intron 3 of the GATA3 gene and its association with breast cancer risk. A case-control study of 206 breast cancer patients and 262 controls was conducted in Iranian women. Several different CT repeat alleles of GATA3 were detected in both the patients and controls. The frequencies of 17 and 18 alleles in patients were significantly lower than controls. Our findings demonstrate that women who carry 17-CT (OR = 0.5; p = 0.003) or 18-CT (OR = 0.41, p = 0.02) alleles of GATA3 gene are at lower risk of developing breast cancer. The highest protection against breast cancer was observed with heterozygotes of 16/17 repeats (OR = 0.12, p = 0.02). Also, the presence of the 17-CT allele has a positive relation with estrogen receptor expression. However, we found that the allelic length of GATA3 polymorphisms had no significant effect on the age onset or grade of the disease, as well as the expression of progesterone receptors and HER2.
Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Dinucleotide Repeats/genetics , GATA3 Transcription Factor/genetics , Genetic Predisposition to Disease , Polymorphism, Genetic/genetics , Adult , Aged , Aged, 80 and over , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Case-Control Studies , Cytosine/physiology , Female , Humans , Iran/epidemiology , Middle Aged , Population Surveillance/methods , Risk Factors , Thymine/physiologyABSTRACT
PTEN/MMAC1/TEP1 encodes a tumor suppressor protein, which regulates cell cycle progression, translation, and apoptosis by blocking the activation of Akt/PKB. The loss of PTEN function increases cell survival and induces tumor invasion. In this study, PTEN promoter status and its correlation with genetic and pathologic parameters were analyzed in genomic DNA from Iranian patients with breast cancer. DNA methylation patterns in the CpG islands were determined by a methylation-specific PCR (MSP) assay. PTEN promoter methylation was found to be present in 37 of 53(70%) tumor tissues and none in 20 normal counterparts. Moreover, promoter methylation was found in patients with heterozygote mutation in the PTEN gene. The pathological history of cancerous tissue sections showed that PTEN gene could be inactivated at the stages III and IV in sporadic breast cancer. These findings suggested that promoter hypermethylation of PTEN might contribute to the progression of sporadic breast cancer in human.
