فهرست مطالب مرتضی عطری

Estrogen-negative breast cancers have different clinical course, prognostic features and treatment response in comparison to estrogen receptor-positive (ER-positive) breast cancers. Human epidermal growth factor receptor 2 (HER2) oncoprotein has found to have a pivotal role in natural cell growth and cell division and is suggested to be directly related to tumor invasiveness in breast cancer patients. The purpose of this study was to retrospectively assess the mammography, ultrasound, and magnetic resonance imaging (MRI) features of estrogen negative breast cancers with and without overexpression of HER2/neu receptor. In this cross-sectional retrospective study, mammographic, ultrasound and MRI features as well as HER2 status were assessed in patients with ER-negative breast cancer that were referred to Cancer Institute of Imam Khomeini Hospital Complex in Tehran from October 2015 to October 2017. Clinicopathologic data and mammography, ultrasound, and MRI features were reviewed and were correlated with HER2 status of estrogen-negative tumors. Of the 172 patients with ER-negative breast cancer, 101 patients were positive for HER2/neu receptor (58.8%). There was a significant correlation between HER2-positivity and tumor type (P=0.004). Among estrogen negative breast cancers, significant association were found between HER2 and tumor histologic grade (P=0.024) and TNM stage (P=0.021). HER2-positive tumors were more likely to present with microcalcification (P=0.007) and have irregular shapes (P=0.034) in mammography than HER2-negative tumors. No association was found between HER-2 status and tumor size, shape, margin, posterior feature, halo or orientation of the tumor in ultrasound. We also found no correlation between HER2 status and MRI features including mass shape or margin, internal enhancement pattern or curve type among estrogen-negative breast cancers. Findings of this study showed that among estrogen-negative breast cancers, HER2/neu positive tumors are more likely to be diagnosed at higher stage and have higher histologic grade at the time of diagnosis. Tumor mass shape and microcalcification in mammography are found to be associated with HER2 status among patients with estrogen-negative breast cancer.

The genus Thymus L. is one of the largest genera of the Lamiaceae family and aromatic plants. Plants of these genera have commercial value due to their essential oils. Thymus eriocalyx is one of the species that is exclusively on the Iranian plateau. In order to investigate the molecular characteristics of Thymus eriocalyx populations in Iran, 10 habitats were selected in Lorestan, Markazi, Hamedan, Kermanshah and Kurdistan provinces (using the DSS method) (50 plant samples). Also, 15 primers with 10 N lengths selected. The molecular data, based on RAPD experiments, divided the populations into five distinct groups. Primers used in this experiment produced 71 bands, which showed 68 polymorphic bands. OPA-05, OPA-17, OPD03 and OPE-20 primers with the highest polymorphism and marker index had excellent ability to study genetic variation in studied species. P2 and P7 populations had the maximum effective allele and p9 population had the minimum value. The highest and lowest mean of expected heterozygosity belonged to P2 and P9 populations, respectively. The highest genetic similarity was observed between P2 and P3 genotypes and the lowest genetic similarity between P2 and P10. The results of analysis of variance (AMOVA) showed that the variation within the populations of these species (68%) is greater than the diversity among populations (32%), which this fact prove the importance of single plant selection and paying attention to individual in Thymus breeding programs.

Miandasht Wildlife Refuge covers 84435 hectars area, located in southwest of North Khorassan province. Mean annual precipitation is 250 mm and altitude range is 912-1085 m. Plants were collected during 2010-2013 by geodesic and eco-phytosociologic methodology. Totally, 260 taxa belonging to 156 genera and 38 families from Angiosperms and Gymnosperms were identified. The results showed that Chenopodiaceae, Asteraceae, Papilionaceae, Brassicaceae and Poaceae, respectively, with the most number of species, are existed in the region. Astragalus is the most divers genus in flora of Miandasht. Based on Raunkiaer classification, 53.46% of species are therophytes, 18.08% hemicryptophytes, 13.46% chamephytes, 8.85% geophytes and 5.38% phanerophytes. Twenty-four (9.23% of all species) belong to thirteen families are endemic to Iran, that fourteen of them are LR and nine species are DD. The chorologic study of plants, showed that specific elements of Irano - Turanian region with 67.31% of frequency are maximum. Percentages of common elements of IT-SS, IT-M, IT-ES are 11.92%, 3.46% and 4.23%, respectively, threeregional elements 8.46% and ploriregional element 4.62% are of total number of plants.

The anatomy، palynology and trichome types of Phlomis olivieri were studied in order to understand the usefulness of these characteristics for systematic purposes. Results showed that vascular bundles were next to each other in the stem، the mesophyll was composed of 1-layered palisade and 3-4 layered spongy parenchyma. There were two collateral vascular bundles in the centre and two small subsidary bundles in the corners of petiole and there were 4 small vascular bundles in the bracteole. Five main types of trichomes (peltate، capitate glandular، stellate، unicellular simple and dendroid trichomes) were observed. The capitate trichomes were subdivided into three groups: type 1 (short stalk)، type 2 (medium or tri-cellular stalk) and type 3 (long or four-cellular stalk). Stellate trichomes were subdivided into two groups: group 1، sessile or short stalked trichomes and group 2، long stalked trichomes. The dendritic trichomes also were reported for the first time in this species. The pollen grains were tricolpate، relatively large، ovate and the exine ornamentation was reticulate and perforate.

Since the identification of the two highly penetrant dominantly inherited genes، BRCA1/2، in the 1990s، a number of other genes have been identified which account for approximately 25% of the genetic basis for hereditary breast cancer. At least 75% are unidentified. The goal of this study is to investigate the presence or absence of a recessive pattern of inheritance in this heterogeneous disease whose possibility has been previously discussed by researchers. In this study we used exome sequencing as the most recent approach for identification of the genetic basis of any disease. The results of exome sequencing were confirmed by Sanger sequencing. Although we did not find any homozygous mutation in this family، however a heterozygous 4bp deletion that led to a frame shift mutation was identified in exon 11 of the BRCA2 gene. Also identified was a heterozygous single nucleotide polymorphism in exon 9 of the STK11 gene. The rs80359352 variation identified in this family is one of the frequent pathogenic mutations in the BRCA2 gene that has been reported in the BIC database. This variation has been previously observed in other ethnic populations such as Caucasians، Hispanics and the Chinese. In this study، for the first time، we report this mutation in Iranian population and its segregation in hereditary breast cancer.

Tanacetum L. is one of the largest genus of Asteraceae family and constitutes one of the most problematic genera in terms of taxonomic complexity، especially concerning genus delimitation against closely related entities. The Tanacetum species are rich in essential oils، bitter components and sesquiterpene lactones. Tanacetum polycephalum Shultz Bip. is a widespread and polymorphic species in Iran. To determine intraspecific variations in T. polycephalum from taxonomic point of view and effective ecological factors، data were collected using special station method. In this way، ten special stations were recognized for T. polycephalum in Hamedan province. Floristic data (floristic marker) were analyzed with Anaphyto software by FCA method. Morphometric data analysis of individual collected from each special station، by using 60 vegetative and reproductive characters، was made with PCO and UPGMA methods and ecologic data were analyzed with CCA method. Analysis of floristic data led to the identification of 4 separate groups that were indicative of the existence of intra-specific diversity. Analysis of morphometric data confirmed the 4-mentioned floristic groups. Analysis of ecologic data showed that ecological factors are effective in grouping and forming special stations diversity، accordingly، 3 phenoecodeme are identifiable and can be introduced.

Thymus eriocalyx (Ronniger) Jalas belongs to the family Lamiaceae. Among different species of Thymus, distributed in the world, 18 species are growing in Iran, of which four species are endemic. To study the variation of essential oils among population individuals of this species in Iran D.S.S. (Determination of special station) method was used. In this study, the aerial parts of 5 individuals of Thymus eriocalyx were collected from 10 special stations, at full flowering stage for chemical investigation and were dried at room temperature. The essential oil was extracted by hydrodistilation method using a Clevenger-type apparatus. The chemical composition of essential oils was analyzed by GC-FID and GC-MS. Results showed that the highest average yield of essential oil in three replications based on dry weight belonged to the first individual of Te2 population (4.09%), while the lowest was recorded for the second individual of Te10 population (0.21%). Totally, thirty one compounds were identified in the essential oil of 10 studied population individuals. In this study, it is noteworthy that the individuals of a population showed variation among themselves in terms of chemical compositions. Among existing chemical compounds in the essential oil of 50 individuals, the following compounds revealed the variation widely: p-cymene (0.1-20.1%), 1,8-cineole (0.4-29.4%), γ-terpinene (0.1-8.7%), linalool (0.1-82.3%), camphor (0.1-15%), borneol (1.6-22.7%), geraniol (0.1-74.6%), thymol (0.1-57.7%), geranyl acetate (0.1-49.6%), caryophyllene oxide (0.2-9.1%), limonene (0.2-24%) and α-terpineol (0.1-36.2%). The results of the analysis of chemical data using MVSP Software by UPGMA and PCO methods led to the identification of 9 chemotypes as follows of which 7 chemotypes were introduced as new chemotypes: 1-geraniol/geranyl acetate, 2-geraniol, 3- linalool/geraniol/geranyl acetate, 4-linalool,5-α-terpineol/1,8-cineole, 6-geranyl acetate, 7-geraniol/thymol/borneol/1,8-cineole,8-thymol/limonene and 9-thymol/p-cymene/borneol.

In order to evaluate several ecological factors, morphological traits, essential oil productivity and ploidy levels of Thymus eriocalyx (Ronniger) Jalas with uses of DSS method ten natural habitats were selected  in Lorestan, Markazi, Hamadan, Kermanshah and Kurdestan provinces  in Iran. To study and evaluate morphological characters, five complete plant samples and flowering branches were collected from each locality at flowering stage for essential oil extraction in spring season of 2008. Ecological data of ten localities were also recorded. Vegetative and reproductive traits and essential oil quantity of each population were studied. Seeds were also collected in the seed production season to study seed characters, chromosome counting and ploidy level. At least 10 mitotic cells of each population were studied to determine chromosome numbers and ploidy levels. All populations were classified in 4 groups. Results revealed that specimens from "Te9 population" had the highest average length and width of inflorescence leaf, inflorescence leaf length to width ratio, stem leaf length to width ratio, petiole length, calyx tube length, corolla length and the highest average length and width of bracteole. The results of chromosome counting showed that specimens of Te1, Te2, Te3, Te4, Te5, Te6 and Te8 populations were diploid (2n=2x=30) and specimens of Te7, Te9 and Te10 populations were tetraploid (2n=4x=60). The highest essential oil production belonged to Te5 population (3.04%).

Intarspecific and interspecific variations are the main reserves of biodiversity and both are important sources of speciation. On this basis، identifing and recognizing the intra and interspecific variations is important in order to recognition of biodiversity. This research was done to study biodiversity and electrophoresis comparison of seed storage proteins in the populations of the two species of the genus Achillea in Hamadan and Kurdistan provinces using of the method of determination of special station (DSS). For this purpose، 12 and 9 special stations were selected for the species A. tenuifolia and A. biebresteinii using the data published in the related flora. Seed storage proteins were extracted and then studied using electrophoresis techniques (SDS-PAGE). In survey of all special stations، 120 plant species were distinguished as associated species. The results of the floristic data for the both species determined six distinctive groups that indicated the existence of intraspecific diversity in this species. The result of analysis of ecological data and seed storage proteins for the two species was in accordance with the floristic data and showed six distinctive groups. The existence of the bands of no. 4، 5، 8، 12 and 13 in the special stations of A. tenuifolia and the bands of 14، 15 and 16 in the special stations of A. biebresteinii o separated the populations of the species in two quite different and distinctive groups.

The genus Artemisia (Asteraceae) with about 200-500 species، is one of the largest genus in Anthemidae. In order to study intraspecific diversity in Artemisia spicigera in the North-West of Iran، D. S. S. method was used in this research work. Eight special stations were determined using D. S. S. method for A. spicigera and floristic-ecologic data collected from each special station. In the survey of all special stations، 75 plant species were distinguished as associated species. As the result of analysis of floristic data، as floristic marker، 6 groups were determined. This groupment distinguished the existence of intraspecific diversity in A. spicigera. Analysis of ecologic data was also confirmed the above mentioned groupment. Seed storage proteins were subjected to electrophoresis to determine the level and kind of intraspecific diversity. The results were also in accordance with the results of floristic and ecological results. Existence of differences regarding number and density of the protein bands indicated the intraspecific diversity in the populations of A. spicigera. Therefore، in this species، the groupment that introduced by floristic marker، was confirmed by ecological and electrophoresis data as well. This means that floristic groupment can only be used as a cost-effective and efficient method to stud intraspecific diversity.

Breast cancer is among the most frequent disorders among the world. BRCA1 gene was known as a tumor suppressor gene which its loss could be resulted in various destructions in genome. Therefore, changes occurred in its expression level could lead to increasing the effects of oncogene activity on breast cells. RT-PCR and Q-RT-PCR were used for detecting BRCA1 expression status among 27 primary affected breast cancer patients. The association between its expression status and histopathologic data had been evaluated by statistical assays. Eighty-five percent of patients showed BRCA1 expression and this expression as well as its quantity had significant associations with tumor grade. It was found that tumors with low levels of BRCA1 expression tend to have higher grades. BRCA1 has an important role in suppressing breast tumorogenesis. Corresponding to some of the previous reports, our findings revealed the role of decreasing in BRCA1 expression level as one of the factors which allows tumors to progress.

In this study, 30 specimens (6 populations) from long-winged species of Onobrychis sect. Onobrychis including O. verae Širj., O. gontscharovii Vassilcz., O. ptychophylla Širj. & Rech. f., O. sosnovskyi Grossh. and O. araxina Schischkin were collected from their natural habitats in Iran. The specimens were biometrically assessed using 45 quantitative and 15 qualitative morphological characters. In order to study the genetic variations of different species, nucleotide sequence data from the internal transcribed spacer of the nuclear rRNA genes (ITS) were obtained. Data regarding longitude, latitude, altitude, slope inclination, slope direction, substrate, min/max annual temperatures, number of rainy days, annual precipitation as well as soil traits including texture, electrical conductivity, organic carbon, total nitrogen, available phosphorus and potassium, total neutralizing value, pH, and saturation percentage were recorded in each sample site. Cluster analysis of morphological characters showed two major groups separating northwest species from northeast ones. Furthermore, the ITS data analysis results showing two main groups, which are exactly in concordance with morphological groups. Also canonical correspondence analysis (CCA) of ecological data showed the precipitation, rainy days, sand% and silt% as the most effective factors for this separation. Furthermore it showed the effect of ecological factors on each species. Onobrychis araxina Schischkin is recorded for the first time from Azerbaijan Gharbi province, Iran. An identification key to the long-winged species of section Onobrychis in Iran is presented.

Thymus L. is one of the largest genus of Lamiaceae family. This species had cammercial values due to containing essential oils and also its wide applications in food and pharmaceutical industries. From this genus، 18 species have been identified in Iran. Because of the gene flow potentiality among populations، a high morphological diversity exists among them. Thymus eriocalyx (Ronniger) Jalas is one of the species of this genus that is distributed only in west of Iran and also north of Iraq to determine intraspecific variations in T. eriocalyx from taxonomic point of view and effective ecological factors، data were collected using special station method. In this way، ten special stations were recognized for T. eriocalyx in west of Iran. Results from floristic data analysis (floristic composition of each special station) with MVSP software by PCO method، led to the identification of 6 separate groups that was indicative of the existence of intraspecific diversity. Furthermore morphometric data analysis of individual collected from each special station، by using 33 vegetative and reproductive characters، with PCO and UPGMA methods، confirmed 5-mentioned floristic groups. Ecologic data analysis with CCA method showed that various ecological factors are effective in grouping and forming special stations diversity، so that among studied factors، altitude، soil texture and permeability and slop direction factors were all effective in groupment of special stations. On this base، at least 3 ecodemes were identifiable and thus، could be introduced.

Regarding economic, medicinal, food and decorative importance of Artemisia genus, this study was carried out to determination of intraspecific diversity in the Artemisia incana populations collected from East Azerbaijan. To study of intraspecific diversity in A. incana in East-Azerbaijan D.S.S. method was used. Six special habitats of this population were recognized. Seeds of populations as well asand floristic-ecologic data were collected from each special habitat. Seed storage proteins were subjected for electrophoresis studies. In survey of all special habitats, 54 species were distinguished as associated species. Analysis of floristic data (Floristic compositions of each special habitat as floristic marker) led to identification of 4 separate groups that was indicated the existence of intraspecific diversity in this species. Analysis of ecologic data was also confirmed the groupment. The analysis of seed storage protein electrophoresis banding pattern showed three quite obvious groups. In the survey of electrophoresis pattern, existence of differences regarding number and density of the protein bands indicating existence of intraspecific diversity in the populations of A. incana. Therefore in this species, the grouping that introduced with floristic marker, confirmed also with ecological and electrophoresis markers. This means that floristic grouping can only be used as a cost-effective and efficient method for studying of intraspecific diversity.

Inadequate folate intake could be associated with increased breast cancer risk. The aim of the present study was to assess the folate intake by designed Food Frequency Questionnaire (FFQ) using plasma folate concentration. This analytic cross-sectional study was conducted to evaluate the validity of the semi-quantitative FFQ (136 items) in 152 women with confirmed breast malignancy aged between 35 - 85 years old.. Folate plasma level was assessed by means of automated electrochemiluminescence. The Pearson and partial correlation coefficients were performed between the plasma level of folate and crude, total and energy-adjusted (residual) folate intakes. Area under ROC curve (AUC), sensitivity, specificity, positive and negative predictive values and odds ratio were fulfilled in two models in order to achieve validity assessment. The folate plasma level was significantly correlated with total intake of vegetables, bread and cereal groups (p=0.001) and also with total intake of fruits (p=0.001) and dairy products (p=0.026). After adjusting for confounders, the folate plasma levels were correlated significantly with daily (β=0.39), and residual (β=0.41) folate intake levels (p=0.001). The area under ROC curves in model I (folate plasma level <5.9 ng/ml) was 0.74 (95%CI=0.63-0.85) and for model II (folate plasma level <10.0 ng/ml) was estimated as 0.61(95%CI= 0.51- 0.71). Model I indicated more appropriate predictive value (p=0.001) of folate intake assessment via FFQ. The results of this study showed that FFQ described in this study could be a valid and appropriate tool for assessing folate intake status in dietary content of breast cancer patients and also could be representative and valid for assessing the folate rich-food intake status.

Astragalus is the largest genus of vascular plants. This genus has 2500-3000 species and 250 sections. In regard to economic and medicinal importance of Astragalus genus, this study, was carried out to determine and to distinguish of intraspecific diversity in phenolic components of Astragalus verus in the west of Iran. For this reason, leave phenolic components belonging to 20 different stations were extracted and analyzed by TLC (Thin Layer Chromatography), to examine the presence or absence of three flavonoidic standards, such as flavones, quercetine and rutin. Finally, data of flavonoid studies were analyzed by MVSP (Multivariate Statistical Package) and SPSS (Statistical Package for the Social Science) softwares with WARD, PCA (Principle Component Analysis) and UPGMA (Unweighted Pair Group Method with Arithmetic mean) methods. Results of flavonoid studies showed intraspecific diversity in chemical components (chemotype) level. The results showed different phenolic groups of Astragalus verus from different stations with different ecological conditions. The studied ecological factors included soil texture, pH, EC, elevation, latitude and longitude. Ecological data analysis showed that, among studied ecological factors, elevation from sea level has the most important role in observed intraspecisic diversity of Astragalus verus in the west of Iran.

Onobrychis melanotricha (Fabaceae) is an endemic perennial herb in Iran and has two varieties. For investigating on infraspecific variation within O. melanotricha, 14 releves were performed in its different habitats in Hamedan province according to the Braun-Blanquet method and samples were gathered using phytosociological approach. Results showed that each variety occupies one of main mountainous and sub-mountainous habitats. They correlate together by a continuous gradient in morphological characters. In addition, different patterns of variation and related effective factors are discussed. O. melanotricha var. ecbatanaica is described and illustrated from Hamedan Province as a new variety. It differs from the type variety by having the large simple leaves.

Onobrychis Miller is the second largest genus of Fabaceae in Iran with nearly 60 species. These species are used as valuable forage plants. Onobrychis sect. Onobrychis with nearly 15 species in Iran is one of the important sections of the genus. Onobrychis transcaspica V. Nikitin, is one of the species of this section that is distributed in NE of Iran. To determine intraspecific variations in O. transcaspica from taxonomic point of view and effective ecological factor, data were collected using special station method. In this way, four special stations were recognized for O. transcaspica in NE of Iran. Results from floristic data (Floristic composition of each special station) analysis with MVSP software by PCO method, led to identification of 3 separate groups that was indicative of existence of intraspecific diversity. Morphometric data analysis of individual collected from each special station, by using 65 vegetative and reproductive characters, with PCO and UPGMA methods, confirmed 3 mentioned floristic groups. Ecologic data analysis with CCA Method showed the presence of 3 phenoecodeme based on 3 morphologic groups resulting from altitudinal variations.

Introduction & Breast cancer is the most common malignancy in adult female population. Great variations exist in incidence and mortality rate of this cancer in different populations. One of the most important and central factors that can greatly affect mortality of a cancer in a population is the stage of cancer which comes under medical attention. In this study, we describe characteristics of 1500 cases of breast cancer at the time of diagnosis and evaluate probable association between some factors and stage of cancer in which cancer comes under medical attention. This retrospective study reviewed files of 1500 cases of female breast cancer. These cases had been referred to a breast cancer private clinic and diagnosis of breast cancer was confirmed by pathologic study. Data about following factors were extracted from files: age of patients, educational level, profession, interval between seeking medical attention and diagnosis confirmation, family history of breast cancer in first-degree relatives, method of diagnosis, results of mammography, tumor size, number of involved lymph nodes, total number of resected lymph nodes, and pathologic stage of tumor. All data of been obtained at the time of diagnosis. Mean age of patients was 49.38± 10.46 years. From patients with known size of tumor, 74.5% had a size of more than 2 cm in our population and in patients with known stage of disease, 78.3% of patients were stage 2 or more which means that they had at least one involved lymph node. On an average, an interval of 2.73 ±1.15 years existed between the time of suspicion and time of definite diagnosis. Finally we conclude that stage of breast cancer at presentation is higher in our country when compared with western countries. This difference is both the result of lower compliance of patients and defects in public services.

The repression of retinoic acid receptor-β2 (RARβ2) expression is a concerning aspect of breast cancer, which is often induced by hypermethylation at promoter of the gene. We aimed to explore the correlation of plasma folate, vitamin B12 and total homocysteine (tHcy) levels with hypermethylation status of RARβ2 gene among Iranian breast cancer patients. The hypermethylation status was investigated in 137 specimens tissues from primary breast cancer patients aged 28-85 years thorough methylation-specific PCR. Hypermethylation at RARβ2 gene was observed in 36.5 %. The hypermthylated RARβ2 associated with younger age at diagnosis and negative family history of breast cancer. The plasma level of folate was found lower in cases aged ≥48 years with hypermethylated RARβ2 gene (P<0.05). In contrast the level of tHcy was shown higher in cases aged <48 y (P<0.05). The risk of hypermethylation at RARβ2 gene increased with low plasma levels of folate (OR=0.21, 95%CI: 0.05-0.88) and vitamin B12 (OR=0.04, 95%CI: 0.01-0.92) and high plasma level of tHcy (OR=7.55, 95%CI: 1.07-25.7) in cases older than 48y. Low plasma levels of folate, Vitamin B12 and high plasma level of total homocysteine could have important roles as prognostic factors in hypermethylation status of RARβ2 gene in breast cancer.

Little information is available regarding genetic variation in Triticum boeoticum, as a common wild wheat relative in Iran. In order to study floristic, phytochemical and molecular classification of this species, an analysis was conducted on populations of the T. boeoticum collected from different regions of Iran. All three markers nearly showed a high variability in T. boeoticum populations. In another word, distinguished grouping of populations in floristic method was confirmed by both phytochemical and molecular methods. The results from our study indicate that floristic classification in some way is still useful, efficient, and economic tools for characterizing the amount and distribution of genetic variation in natural populations.

Seed proteins were studied in 21 populations of 17 Bromus species and varieties growing in Iran. In total 83 protein bands were observed in all the species studied. The number of bands and their density varied in these species, indicating their genetic differences. Some specific bands were observed in most of the species indicating the presence of specific genes in these species as a result of species diversification. Such specific protein bands may be of use in the Bromus species identification. Different clustering and ordination methods showed separation of the species of sect. Bromus from the species of the sect. Pnigma, indicating the use of seed proteins in taxonomic delimitation of these two sections.

The translation of estrogen receptor-α (ERα) is vital in therapeutic regimens in breast cancer. The repression of its expression could be attributed to regional CpG island methylation in exon1. We aimed to explore the association of plasma levels of folate, vitamin B12 and total homocysteine (tHcy) with the hypermethylation status of ERα genes in breast cancer patients. The hypermethylation status was determined in dissected tissues from 137 primary breast cancer patients aged 28-85 years, using methylation-specific PCR. In addition, the plasma levels of folate and vitamin B12 of the patients were assessed by automated chemiluminescence, and their total plasma homocysteine was determined by HPLC. The logistic regression analysis was used for analyzing the data after adjusting for potential confounding factors. Hypermethylation at ERα was observed in 51.1% of the participants. It was related positively to smoking history and duration of exposure to estradiol, and inversely with ER translation. After adjustments for confounding factors, an inverse association was also found between the hypermethylation status of ERα gene and the plasma levels of folate (OR=0.187; 95%CI, 0.052-0.668) and vitamin B12 (OR=0.185; 95%CI, 0.036-0.953). The data also showed that the risk of hypermethylation at ERα gene increased with the high plasma levels of tHcy (OR=9.61; 95%CI, 1.26-73.2). It may be concluded that a high plasma tHcy level can potentially increase the risk of hypermethylation of the ERα gene, while plasma folate and vitamin B12 levels may reduce the risk, in cancer patients