ESR1 single nucleotide polymorphisms predict breast cancer susceptibility in the central European Caucasian population.

Estrogen and progesterone hormones are key regulators of a wide variety of biological processes. In addition to their influence on reproduction, cell differentiation and apoptosis, they affect inflammatory response, cell metabolism and most importantly, they regulate physiological breast tissue proliferation and differentiation as well as the development and progression of breast cancer. In order to assess whether genetic variants in the steroid hormone receptor gene ESR1 (estrogen receptor alpha) had an effect on sporadic breast cancer susceptibility, we assessed 7 ESR1 single nucleotide polymorphisms (SNPs) for associations with breast cancer susceptibility and clinical parameters in 221 breast cancer patients and 221 controls, respectively. We identified ESR1 intron SNP +2464 C/T (rs3020314) and ESR1 intron SNP -4576 A/C (rs1514348) to correlate with breast cancer susceptibility and progesterone receptor expression status. Patients genotyped CT for ESR1 intron SNP +2464 (rs3020314) (p ≤ 0.045) or genotyped AC for ESR1 intron SNP -4576 (rs1514348) (p ≤ 0.000026) were identified to carry a significant risk as to the development of breast cancer in the Central European Caucasian population (both together: p ≤ 0.000488). Our study could confirm previous associations and revealed new associations of SNP rs1514348 with susceptibility to breast cancer and clinical outcome, which might be used as new additional SNP markers.

DNMT1 genetic polymorphisms affect breast cancer risk in the central European Caucasian population.

INTRODUCTION: DNA methylation of CpG islands within the promoter region of genes is an epigenetic modification with an important role in the development of cancer and it is typically mediated by DNA methyltransferases (DNMTs). In cancer cells, global hypomethylation of the genome as a whole and regional hypermethylation of CpG islands have been reported. Four groups of DNMTs have been identified: DNMT1, DNMT2 (TRDMT1), DNMT3A and DNMT3B. DNMT2 uses the catalytic mechanism of DNMTs, but does in fact methylate RNA. Little is known about the significance of these genes in human breast cancer. In the study presented herein, we analyzed five distinct DNMT single SNPs with regard to potential associations with breast cancer risk. CASE DESCRIPTION: In this study, we genotyped 221 female Caucasian breast cancer patients and 221 female Caucasian healthy controls, and we used five allele-specific real-time polymerase chain reaction (qPCR) assays. We selected one locus within the DNMT1 gene and two loci within the DNMT3A and DNMT3B genes, respectively. Statistics were calculated using the chi-squared and Fisher's exact tests, and correlated with clinical parameters such as age, diagnosis, histology, TNM stage, hormonal receptor status, human epidermal growth factor receptor 2 (HER2) status, response to treatment and survival. Statistically significant results were obtained for correlations with the DNMT1 gene. DISCUSSION AND EVALUATION: Five genomic loci within the DNMT1, DNMT3A and DNMT3B genes were assessed. Statistical significance (P = 0.030) was identified for DNMT1 SNP (A201G, rs2228612): six women within the control group were GG homozygous (variant), while this mutation was absent in the breast cancer group. CONCLUSIONS: We conclude that women with the DNMT1 SNP (A201G, rs2228612) GG homozygous genotype (variant) have a lower risk of developing breast cancer compared to heterozygous or wildtype genotypes. To date, alterations within the DNMT1 gene have not been reported to be associated with cancer in the Caucasian population.

Axillary dissection in primary breast cancer: variations of the surgical technique and influence on morbidity.

Lymphedema of the arm is the most common and impairing complication after breast cancer surgery with axillary lymph node dissection (ALND). Our prospective study evaluated the effect of two different surgical techniques for ALND on postoperative morbidity. Patients were scheduled to undergo ALND. Patients in group 1 (n = 17) underwent the most common and standard technique of ALND, which uses sharp dissection of the tissue and subsequent electro-coagulation of bleedings. Patients in group 2 (n = 17) underwent a modified standard technique of ALND with clamping and ligatures of all resection margins. Postoperative wound secretion was quantified and patients were followed up for 6 months to assess long-term morbidity. The variations in surgical technique had no significant influence on the outcome variables. However, patients in group 2 showed a tendency to less wound secretion (713 versus 802 mL; P = nonsignificant), a decreased rate of immediate postoperative seromas (11.8 versus 23.5%; P = nonsignificant) and less lymphedema after 3 months (29.4 versus 41.2%; P = nonsignificant). Moreover, the number of resected lymph nodes correlated with the total amount of drained fluid (P = 0.006), the duration of the drain (P = 0.015), and the risk for the development of lymphedema after 3 months (P = 0.016). The described variations in surgical technique had no influence on the outcomes of the patients. The number of resected axillary lymph nodes remains the most important risk factor for treatment-related morbidity. Therefore, a well-balanced choice of the extent of the axillary dissection should be the surgeon's main concern.