The high methylation level of a novel 151-bp CpG island in the ESR1 gene promoter is associated with a poor breast cancer prognosis.

BACKGROUND: The ESR1 gene suffers methylation changes in many types of cancers, including breast cancer (BC), the most frequently diagnosed cancer in women that is also present in men. Methylation at promoter A of ESR1 is the worse prognosis in terms of overall survival; thus, the early detection, prognostic, and prediction of therapy involve some methylation biomarkers. METHODS: Therefore, our study aimed to examine the methylation levels at the ESR1 gene in samples from Mexican BC patients and its possible association with menopausal status. RESULTS: We identified a novel 151-bp CpG island in the promoter A of the ESR1 gene. Interestingly, methylation levels at this CpG island in positive ERα tumors were approximately 50% less than negative ERα or control samples. Furthermore, methylation levels at ESR1 were associated with menopausal status. In postmenopausal patients, the methylation levels were 1.5-fold higher than in premenopausal patients. Finally, according to tumor malignancy, triple-negative cancer subtypes had higher ESR1 methylation levels than luminal/HER2+ or luminal A subtypes. CONCLUSIONS: Our findings suggest that methylation at this novel CpG island might be a promising prognosis marker.

Breast cancer-related single-nucleotide polymorphism and their risk contribution in Mexican women.

CONTEXT: Four single-nucleotide polymorphisms (SNPs) in Mexican patients and their association with the development of breast cancer (BC). AIMS: This work is focused on determining the association of fibroblast growth factor receptor (rs12196489), TOX3 (rs3803662), human telomerase reverse transcriptase (h TERT, rs10069690), and FTO (rs17817449) polymorphisms and BC in a cohort of Mexican women. SETTINGS AND DESIGN: The study included 56 patients with a confirmed diagnosis of BC and 83 controls. Clinical characteristics were obtained from medical records. SUBJECTS AND METHODS: Genomic DNA from the samples was obtained from lymphocytes, and the genotyping of rs12196489, rs3803662, rs10069690, and rs17817449 polymorphisms was performed by real-time polymerase chain reaction using specific TaqMan probes. Statistical analysis was assessed to evaluate the distribution of genotype frequencies between cases and controls. STATISTICAL ANALYSIS: We used the STATA Statistical Package (version 10.1; STATA Corp., College Station, TX, USA). Student's t-test, χ2 test, or Fisher's exact test was used to evaluate the distribution of genotype frequencies. RESULTS: No statistical differences in allelic and genotypic frequencies were found between patients with BC and controls for SNPs: rs1219648, rs3803662, and rs17817449. Interestingly, according to the χ2 test, a significant difference was exhibited for rs10069690 (odds ratio = 0.095; 95% confidence interval = 0.038-0.214; P < 0.001). CONCLUSIONS: The h TERT (rs10069690) polymorphism might be associated with BC in Mexican women. Nevertheless, additional studies in a larger cohort are required to confirm this association and to possibly use this polymorphism as a potential biomarker in the early diagnosis of BC.