Association of plasma folate, vitamin B12 and homocysteine levels with hypermethylation status of Eralphagene in primary breast carcinoma

The translation of estrogen receptor- a [ERa] 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 ERa 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 ERa 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 ERa 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 ERa 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 ERa gene, while plasma folate and vitamin B12 levels may reduce the risk, in cancer patients

Role of Family History of Neoplastic Disorders in 100 Patients with Primary Breast Cancer

To find whether the family history of neoplasia is a risk factor for breast cancer [BC] in Iran, 100 patients with primary BC were studied. The mean +/- SD of age of the patients was 50 +/- 11 years. In 52% of them left and in 48% right breast was involved. The most frequent pathologic classification was infiltrating ductal carcinoma [IDC]. Tumour size ranged between 0.4 to 6 centimeters. Sixty two% of the subjects had axillary lymph node involvement, and 42% had family history of at least one neoplastic disorder, excluding breast cancers in their pedigrees. The total number of neoplasias was 108 in which BC 27%, colon, uterus, and leukaemia, each 7% were among the more frequent cancers in the pedigrees, and among 29 cases with BC, 19 pedigrees had just one case of BC. The origin of neoplasia was more maternal, with maternal/paternal ratio of 34/6. Comparative study using 100 healthy control subjects, revealed a strong association between a family history of any neoplasia and occurrence of breast cancer in family [crude OR = 7.63 with P = 0.0001; in cases 42 out of 100 had family history of neoplasia versus 9 out of 100 in controls]. Further studies needed to evaluate the role of family history of neoplastic disorders for the risk of developing BC