Background Tumor Necrosis Factor-α (TNF-α) has been implicated in the pathogenesis of insulin resistance and obesity. The increased expression of TNF-α in adipose tissue has been shown to induce insulin resistance, and a polymorphism at position -308 in the promoter region ofTNF-α has been shown to increase transcription of the gene in adipocytes. Aim of this study is to investigate the role of the G-308A TNFα variant in obesity and to study the possible influence of this mutation on body fat distribution and on measures of obesity (including Fat Free Mass, Fat Mass, basal metabolic rate), insulin resistance (measured as HOMAIR), and lipid abnormalities. The G-308A TNFα polymorphism has been studied in 115 patients with obesity (mean BMI 33.9 ± 0.5) and in 79 normal lean subjects (mean BMI 24.3 ± 0.3). Methods The G-308A variant, detected by PCR amplification and Nco-1 digestion, determines the loss of a restriction site resulting in a single band of 107 bp [the (A) allele]. Results The (A) allele frequencies of the G-308A TNFα polymorphism were 13.1% in the obese group and 14.6% in the lean subjects, with no significant difference between the two groups. Furthermore, no association was found with BMI classes, body fat distribution, HOMAIR, and metabolic abnormalities. Conclusions Our study did not detect any significant association of the G-308A TNFα polymorphism with obesity or with its clinical and metabolic abnormalities in this population. Our data suggests that, in our population, the G-308A TNFα polymorphism is unlikely to play a major role in the pathogenesis of these conditions.

Background The contribution of BRCA1 and BRCA2 to the incidence of male breast cancer (MBC) in the United Kingdom is not known, and the importance of these genes in the increased risk of female breast cancer associated with a family history of breast cancer in a male first-degree relative is unclear. Methods We have carried out a population-based study of 94 MBC cases collected in the UK. We screened genomic DNA for mutations in BRCA1 and BRCA2 and used family history data from these cases to calculate the risk of breast cancer to female relatives of MBC cases. We also estimated the contribution of BRCA1 and BRCA2 to this risk. Results Nineteen cases (20%) reported a first-degree relative with breast cancer, of whom seven also had an affected second-degree relative. The breast cancer risk in female first-degree relatives was 2.4 times (95% confidence interval [CI] = 1.4–4.0) the risk in the general population. No BRCA1 mutation carriers were identified and five cases were found to carry a mutation in BRCA2. Allowing for a mutation detection sensitivity frequency of 70%, the carrier frequency for BRCA2 mutations was 8% (95% CI = 3–19). All the mutation carriers had a family history of breast, ovarian, prostate or pancreatic cancer. However, BRCA2 accounted for only 15% of the excess familial risk of breast cancer in female first-degree relatives. Conclusion These data suggest that other genes that confer an increased risk for both female and male breast cancer have yet to be found.

Background Mutations in BRCA1 and BRCA2 account for approximately 50% of breast cancer families with more than four affected cases, whereas exonic mutations in p53, PTEN, CHK2 and ATM may account for a very small proportion. It was recently reported that an intronic variant of p53 - G13964C - occurred in three out of 42 (7.1%) 'hereditary' breast cancer patients, but not in any of 171 'sporadic' breast cancer control individuals (P = 0.0003). If this relatively frequent occurrence of G13964C in familial breast cancer and absence in control individuals were confirmed, then this would suggest that the G13964C variant plays a role in breast cancer susceptibility. Method We genotyped 71 familial breast cancer patients and 143 control individuals for the G13964C variant using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis. Results Three (4.2%; 95% confidence interval [CI] 0–8.9%) G13964C heterozygotes were identified. The variant was also identified in 5 out of 143 (3.5%; 95% CI 0.6–6.4%) control individuals without breast cancer or a family history of breast cancer, however, which is no different to the proportion found in familial cases (P = 0.9). Conclusion The present study would have had 80% power to detect an odds ratio of 4.4, and we therefore conclude that the G13946C polymorphism is not a 'high-risk' mutation for familial breast cancer.

Gene Expression Omnibus numbers only. This dataset is associated with the following publication: Mesnage, R., A. Phedonos, M. Arno, S. Balu, C. Corton, and M. Antoniou. Transcriptome profiling reveals bisphenol A alternatives activate estrogen receptor alpha in human breast cancer cells. TOXICOLOGICAL SCIENCES. Society of Toxicology, 158(2): 431-443, (2017).

Background Mutations in the CHK2 gene at chromosome 22q12.1 have been reported in families with Li-Fraumeni syndrome. Chk2 is an effector kinase that is activated in response to DNA damage and is involved in cell-cycle pathways and p53 pathways. Methods We screened 139 breast tumors for loss of heterozygosity at chromosome 22q, using seven microsatellite markers, and screened 119 breast tumors with single-strand conformation polymorphism and DNA sequencing for mutations in the CHK2 gene. Results Seventy-four of 139 sporadic breast tumors (53%) show loss of heterozygosity with at least one marker. These samples and 45 tumors from individuals carrying the BRCA2 999del5 mutation were screened for mutations in the CHK2 gene. In addition to putative polymorphic regions in short mononucleotide repeats in a non-coding exon and intron 2, a germ line variant (T59K) in the first coding exon was detected. On screening 1172 cancer patients for the T59K sequence variant, it was detected in a total of four breast-cancer patients, two colon-cancer patients, one stomach-cancer patient and one ovary-cancer patient, but not in 452 healthy individuals. A tumor-specific 5' splice site mutation at site +3 in intron 8 (TTgt [a → c]atg) was also detected. Conclusion We conclude that somatic CHK2 mutations are rare in breast cancer, but our results suggest a tumor suppressor function for CHK2 in a small proportion of breast tumors. Furthermore, our results suggest that the T59K CHK2 sequence variant is a low-penetrance allele with respect to tumor growth.

Datasets in Gene Expression Omnibus used in the study ORD-020969: Genomic effects of androstenedione and sex-specific liver cancer susceptibility in mice. This dataset is associated with the following publication: Rooney, J., N. Ryan, B. Chorley, S. Hester, E. Kenyon, J. Schmid, B. George, M. Hughes, Y. Sey, A. Tennant, D. MacMillan, J. Simmons, C. McQueen, A. Pandiri, C. Wood, and C. Corton. Genomic effects of androstenedione and sex-specific liver cancer susceptibility in mice. TOXICOLOGICAL SCIENCES. Society of Toxicology, 160(1): 15–29, (2017).

Raw data and figures for Bisphenol A activates EGFR and ERK promoting proliferation, tumor spheroid formation and resistance to EGFR pathway inhibition in estrogen receptor-negative inflammatory breast cancer cells manuscript. This dataset is associated with the following publication: Sauer, S.J., M. Tarpley, I. Shah , A.V. Save, H.K. Lyerly, S.R. Patierno, K.P. Williams, and G.R. Devi. (Carcinogenesis) Bisphenol A activates EGFR and ERK promoting proliferation, tumor spheroid formation and resistance to EGFR pathway inhibition in estrogen receptornegative inflammatory breast cancer cells. CARCINOGENESIS. Oxford University Press, Cary, NC, USA, 38(3): 252–260, (2017).

,Insulin resistance has wide-ranging effects on metabolism but there are knowledge gaps regarding the tissue origins of systemic metabolite patterns, and how patterns are altered by fitness and metabolic health. To address these questions, plasma metabolite patterns were determined every 5 min during exercise (30 min, ~45% of V̇O2peak, ~63 W) and recovery in overnight-fasted sedentary, obese, insulin resistant women under controlled conditions of diet and physical activity. We hypothesized that improved fitness and insulin sensitivity following a ~14 wk training and weight loss intervention would lead to fixed workload plasma metabolomics signatures reflective of metabolic health and muscle metabolism. Pattern analysis over the first 15 min of exercise—regardless of pre- vs. post-intervention status—highlighted anticipated increases in fatty acid tissue uptake and oxidation (e.g., reduced long-chain fatty acids), diminution of non-oxidative fates of glucose (e.g., lowered sorbitol-pathway metabolites and glycerol-3-galactoside [possible glycerolipid synthesis metabolite]), and enhanced tissue amino acid use (e.g., drops in amino acids; modest increase in urea). A novel observation was that exercise significantly increased several xenometabolites (“non-self” molecules, from microbes or foods), including benzoic acid/salicylic acid/salicylaldehyde, hexadecanol/octadecanol/dodecanol, and chlorogenic acid. In addition, many non-annotated metabolites changed with exercise. Although exercise itself strongly impacted the global metabolome, there were surprisingly few intervention-associated differences despite marked improvements in insulin sensitivity, fitness, and adiposity. These results, and previously-reported plasma acylcarnitine profiles, support the principle that most metabolic changes during sub-maximal aerobic exercise are closely tethered to absolute ATP turnover rate (workload), regardless of fitness or metabolic health status.,Supporting Materials include graphs of blood patterns of metabolites in adult women during a sub-maximal exercise bout and recovery period, and primary data in spreadsheet format on model performance, exercise and recovery, and correlation statistics for metabolites.,Journal information -- Am J Physiol, Endo & Metabolism, Exercise plasma metabolomics and xenometabolomics in obese, sedentary, insulin-resistant women: impact of a fitness and weight loss intervention.,,

This dataset contains data for adult male fathead minnows exposed to EE2 (a synthetic estrogen). It is a targeted study on the response of the esr1 gene (expression and DNA methylation profiles) to estrogen exposure. It contains mean and standard deviation for DNA methylation levels per treatment group, and gene expression data.