Background Breast cancer is hormone related, as are cancers of the endometrium, ovary, and prostate. Several studies have suggested that higher extracellular levels of androgens are associated with breast cancer risk, while biological evidence indicates that androgens are protective. The codon 49 alanine to threonine substitution (A49T), codon 89 valine to leucine substitution (V89L) and TA repeat polymorphisms of the steroid 5α-reductase type II (SRD5A2) gene are considered functional with respect to enzyme activity converting testosterone into dihydrotestosterone. To test the hypothesis that these three polymorphisms are associated with risk of breast cancer, a case–control study was conducted with patients of Aichi Cancer Center Hospital. Methods The cases were 237 patients histologically diagnosed with breast cancer, and the controls were 185 noncancer outpatients. DNA from peripheral blood was genotyped by PCR methods. Results The threonine allele of A49T was not found in our subjects. Compared with the V/V genotype of V89L, the L/L genotype was associated with a decreased risk (crude odds ratio [OR] = 0.61, 95% confidence interval [CI] = 0.36–1.05). This was also the case for the TA(9/9) genotype, with an OR of 0.58 (95% CI = 0.13–2.63) relative to TA(0/0). Among women with the TA(0/0) genotype, however, the OR for the L/L genotype was 0.46 (95% CI = 0.24–0.88) compared with the V/V genotype, and those with the V/V and TA(0/0) genotypes had the highest risk. The haplotype with the L and TA(9) repeat alleles was not found. Conclusion This study is the first to our knowledge focusing on Japanese women, suggesting that SRD5A2 polymorphisms might have an association with breast cancer risk. Further large-sample studies will be required to confirm the association and to assess any interactions with environmental factors.

Background The relationship between breast cancer and organochlorine exposure is controversial and complex. As estrogen receptor positive and negative breast cancer may represent different entities of the disease, this study was undertaken to evaluate organochlorines influence on breast cancer risk and survival according to receptor status. Methods The background material stems from the Copenhagen City Heart Study (Denmark 1976-78). The breast cancer risk was investigated in a cohort nested case-control design including 161 cases and twice as many breast cancer free controls. The cases served as a cohort in the survival analysis. Serum organochlorine concentrations were determined by gaschromotography. Results The observed increased breast cancer risk associated with exposure to dieldrin derived from women who developed an estrogen receptor negative (ERN) tumor (Odds ratio [OR] I vs. IV quartile, 7.6, 95% confidence interval [95% CI] 1.4-46.1, p-value for linear trend 0.01). Tumors in women with the highest dieldrin serum level were larger and more often spread at the time of diagnosis than ERP tumors. The risk of dying was for the remaining evaluated compounds higher among patients with ERP breast cancer when compared to those with ERN. In the highest quartile of polychlorinated biphenyls (ΣPCB) it was more than 2-fold increased (Relative risk [RR] I vs. IV quartile, 2.5, 95% CI 1.1-5.7), but no dose-response relation was apparent. Conclusion The results do not suggest that exposure to potential estrogenic organochlorines leads to development of an ERP breast cancer. A possible adverse effect on prognosis of hormone-responsive breast cancers needs to be clarified.

List of biomarker genes used to predict estrogen receptor activity in MCF-7 cells; list of microarray accession numbers used in the study. This dataset is associated with the following publication: Vanduyn, N., B. Chorley , R. Tice, R. Judson , and C. Corton. Moving Toward Integrating Gene Expression Profiling into High-throughput Testing:A Gene Expression Biomarker Accurately Predicts Estrogen Receptor α Modulation in a Microarray Compendium. TOXICOLOGICAL SCIENCES. Society of Toxicology, 151(1): 88-103, (2016).

Background It is known that use of hormone replacement therapy (HRT) by postmenopausal women increases the risk of breast cancer. Method In this study, oestrogen receptor (ER)-α expression is examined using standard immunoperoxidase technique. Results Normal breast samples of 11 Australian postmenopausal women have been included in the ER-α study; the result showed a strong correlation (r2 = 0.80) between ER-α expression in normal breast epithelial cells and body mass index (BMI) in normal women who currently use HRT. Conclusion This finding confirms that the possibility of increased risk of breast cancer associated with increased ER-α expression in normal breast epithelial cells, in turn associated with high BMI and the use of HRT.

Background The involvement of β2-adrenergic receptor (ADRB2) and β3-adrenergic receptor (ADRB3) in both adipocyte lipolysis and thermogenic activity suggests that polymorphisms in the encoding genes might be linked with interindividual variation in obesity, an important risk factor for postmenopausal breast cancer. In order to examine the hypothesis that genetic variations in ADRB2 and ADRB3 represent interindividual susceptibility factors for obesity and breast cancer, we conducted a hospital-based, case-control study in the Aichi Cancer Center, Japan. Methods A self-administered questionnaire was given to 200 breast cancer patients and 182 control individuals, and pertinent information on lifestyle, family history and reproduction was collected. ADRB2 and ADRB3 genotypes were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism assessment. Results Twenty-five (12.4%) breast cancer patients and 32 (17.6%) control individuals were found to bear a glutamic acid (Glu) allele for the ADRB2 gene (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.38-1.18), and 60 (30.0%) breast cancer patients and 61 (33.5%) control individuals were found to bear an Arg allele for the ADRB3 gene (OR 0.85, 95% CI 0.55-1.31). A significantly lower risk was observed in those who carried the Glu ADRB2 allele and who reported first childbirth when they were younger than 25 years (OR 0.35; 95% CI 0.13-0.99). Conclusion A potential association may exist between risk of breast cancer and polymorphisms in the ADRB2 and ADRB3 genes; further studies in larger samples and/or in different ethnic groups are warranted to investigate this potential association.

Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2060 chemical samples on steroidogenesis via high-performance liquid chromatography followed by tandem mass spectrometry quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a 3 stage screening strategy. The first stage established the maximum tolerated concentration (MTC; ≥ 70% viability) per sample. The second stage quantified changes in hormone levels at the MTC whereas the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were prestimulated with 10 µM forskolin for 48 h to induce steroidogenesis followed by chemical treatment for 48 h. Of the 2060 chemical samples evaluated, 524 samples were selected for 6-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 17β-estradiol and/or testosterone, with 411 chemical samples showing an effect on at least one hormone across the steroidogenesis pathway. Clustering of the concentration-dependent chemical-mediated steroid hormone effects grouped chemical samples into 5 distinct profiles generally representing putative mechanisms of action, including CYP17A1 and HSD3B inhibition. A distinct pattern was observed between imidazole and triazole fungicides suggesting potentially distinct mechanisms of action. From a chemical testing and prioritization perspective, this assay platform provides a robust model for high-throughput screening of chemicals for effects on steroidogenesis. This dataset is associated with the following publication: Karmaus , A., C. Toole, D. Filer , K. Lewis, and M. Martin. (Toxicological Sciences) High-throughput screening of chemical effects on steroidogenesis using H295R human adrenocortical carcinoma cells. TOXICOLOGICAL SCIENCES. Society of Toxicology, 150(2): 323-332, (2016).

RAW DATA, SAS FILES AND DATA MEANS. This dataset is associated with the following publication: Howdeshell, K., C. Rider, V. Wilson , J. Furr , C. Lambright , and E. Gray. Dose addition models based on biologically-relevant reductions in fetal testosterone accurately predict postnatal reproductive tract alterations by a phthalate mixture in rats. TOXICOLOGICAL SCIENCES. Society of Toxicology, 148(2): 488-502, (2015).

Background We conducted the present study to determine whether breast cancer morphology is genetically determined. Methods Using the nationwide Swedish Family Cancer Database, which includes data on 10.2 million individuals and over 25,000 morphology-specific breast cancers, we followed morphological types in familial cancers between mothers and daughters and between sisters. Additionally, we recorded morphological data in women who presented with two primary breast cancers and in those who presented with an invasive and in situ breast cancer. We used kappa statistics to examine the association between genetics and morphology. A kappa value of 0 indicates that the process is random and a value of 1 indicates that it is completely determined (i.e. genetic); values between 0.40 and 0.60 are considered to indicate a moderately determined process. Results The study sample included a total of 25,730 first and 3394 second invasive breast cancers, and 2990 in situ breast cancers. Ductal, lobular, tubuloductal and comedo were the most common invasive types. We identified 164 mother-daughter pairs with breast cancer of a defined morphology, yielding a low kappa value of 0.08. Among 100 sister pairs the kappa value was 0.002. In individuals with two primary breast cancers the kappa values were 0.22 and 0.01 for two invasive and in situ-invasive pairs, respectively. However, for a tumour with a subsequent tumour detected in the contralateral breast less than 1 year later the kappa value was 0.47. Conclusion The data suggest that breast cancer morphology is not genetically determined. However, because of mixed morphologies and the overwhelming prevalence of ductal morphology, the results for rare morphologies should be interpreted with caution.

GEOSite dataset for article 'In vitro transcriptomic analyses reveal pathway perturbations, estrogenic activities, and potencies of data-poor BPA alternative chemicals '. This dataset is associated with the following publication: Matteo, G., K. Leingartner, A. Rowan-Carroll, M. Meier, A. Williams, M. Beal, M. Gagne, R. Farmahin, S. Wickramasuriya, A.J. Reardon, T. Barton-Maclaren, J. Corton, C. Yauk, and E. Atlas. In vitro transcriptomic analyses reveal pathway perturbations, estrogenic activities, and potencies of data-poor BPA alternative chemicals. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 191(2): 266-275, (2023).