title: Association of the hypermethylation status of PTEN tumor suppressor gene with the risk of breast cancer among Kurdish population from Western Iran.
abstract: Breast cancer is the most common cancer with high morbidity and mortality among women worldwide. Aberrant hypermethylation in promoter regions of the tumor suppressor genes such as PTEN gene is a key event in the progression and development of breast cancer. The aim of the present study was to evaluate an association between PTEN gene methylation status with the risk of breast cancer in an Iranian population. We studied 255 individuals, including 103 patients with breast cancer, 102 first-degree female relatives of patients (mother, sister, or daughter of patients), and 50 healthy individuals as a control group. Genomic DNA was extracted from peripheral blood leukocytes, and the PTEN promoter methylation status was detected using methylation-specific PCR (MSP) method with specific methylated and unmethylated primers. In some samples, direct DNA sequencing was used to confirm the results obtained by the MSP method. The frequency of PTEN-methylated (MM) genotype was 6 % in the healthy control group, 23.3 % in relatives of patients, and 41.7 % in patients (χ (2) = 24.62, p < 0.001). There were significant differences in the frequency of PTEN-methylated genotype between healthy control compared to that in patients (χ (2) = 15.1, p < 0.001) and also compared to that in relatives of patients (χ (2) = 6.9, p = 0.009). In the presence of PTEN MM genotype, there was a 3.1-fold susceptibility to breast cancer compared to the UU genotype (p < 0.001). Also, in the presence of PTEN M allele, the risk of breast cancer was 2.71-fold compared to the presence of U allele (p < 0.001). Our findings indicated increased frequency of hypermethylation of PTEN promoter in the studied patients and their relatives that could be considered as one of the epigenetic factors affecting the risk of breast cancer in Iranians.
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Kheirollah
authors.initials: K
authors.lastname: Yari
authors.affiliation: Department of Hematology and Medical Oncology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Payandeh
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. zrahimi@kums.ac.ir.|Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran. zrahimi@kums.ac.ir.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Rahimi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000453:epidemiology / Q000235:genetics* / Q000556:secondary; D018275:Carcinoma, Lobular / Q000453:epidemiology / Q000235:genetics* / Q000556:secondary; D016022:Case-Control Studies; D002648:Child; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D016147:Genes, Tumor Suppressor; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D055815:Young Adult
chemical_list: D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Breast cancer; Epigenetic; Iranian population; Methylation; Methylation-specific PCR; PTEN