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Recent studies have shown that exposure to some nutritional supplements and chemicals in utero can affect the epigenome of the developing mouse embryo, resulting in adult disease. Our hypothesis is that epigenetics is also involved in the gestational programming of adult phenotype by alcohol. We have developed a model of gestational ethanol exposure in the mouse based on maternal ad libitum ingestion of 10% (v/v) ethanol between gestational days 0.5–8.5 and observed changes in the expression of an epigenetically-sensitive allele, Agouti viable yellow (Avy), in the offspring. We found that exposure to ethanol increases the probability of transcriptional silencing at this locus, resulting in more mice with an agouti-colored coat. As expected, transcriptional silencing correlated with hypermethylation at Avy. This demonstrates, for the first time, that ethanol can affect adult phenotype by altering the epigenotype of the early embryo. Interestingly, we also detected postnatal growth restriction and craniofacial dysmorphology reminiscent of fetal alcohol syndrome, in congenic a/a siblings of the Avy mice. These findings suggest that moderate ethanol exposure in utero is capable of inducing changes in the expression of genes other than Avy, a conclusion supported by our genome-wide analysis of gene expression in these mice. In addition, offspring of female mice given free access to 10% (v/v) ethanol for four days per week for ten weeks prior to conception also showed increased transcriptional silencing of the Avy allele. Our work raises the possibility of a role for epigenetics in the etiology of fetal alcohol spectrum disorders, and it provides a mouse model that will be a useful resource in the continued efforts to understand the consequences of gestational alcohol exposure at the molecular level.

Endometrial cancer is the most common malignancy of the female genital tract in developed countries. To identify genetic variants associated with endometrial cancer risk, we undertook a genome-wide association study involving 1,265 endometrial cancer cases from Australia and the UK and 5,190 controls from the Wellcome Trust Case Control Consortium. Genotype frequencies in cases and controls were compared for 519,655 SNPs. Forty-seven SNPs that showed evidence of association with endometrial cancer in stage 1 were genotyped in 3,957 additional cases and 6,886 controls. We identified an endometrial cancer susceptibility locus close to HNF1B on chromosome 17q (SNP rs4430796: P=7.1×10−10), that is also associated with risk of prostate cancer and is inversely associated with type 2 diabetes.

The purpose of this study was to assess the safety and efficacy of progressive resistance training (PRT) in breast cancer. Randomized controlled trials (RCTs) published to November 2013 that reported on the effects of PRT (>6 weeks) on breast cancer-related lymphedema (BCRL) (incidence/exacerbation, arm volume, and symptom severity), physical functioning (upper and lower body muscular strength), and health-related quality of life (HRQoL) in breast cancer patients were included. Of 446 citations retrieved, 15 RCTs in 1,652 patients were included and yielded five studies on BCRL incidence/exacerbation (N = 647), four studies on arm volume (N = 384) and BCRL symptom severity (N = 479), 11 studies on upper body muscular strength (N = 1,252), nine studies on lower body muscular strength (N = 1,079), and seven studies on HRQoL (N = 823). PRT reduced the risk of BCRL versus control conditions [OR = 0.53 (95% CI 0.31-0.90); I2 = 0%] and did not worsen arm volume or symptom severity (both SMD = -0.07). PRT significantly improved upper [SMD = 0.57 (95% CI 0.37-0.76); I2 = 58.4%] and lower body muscular strength [SMD = 0.48 (95% CI 0.30-0.67); I2 = 46.7%] but not HRQoL [SMD = 0.17 (95% CI -0.03 to 0.38); I2 = 47.0%]. The effect of PRT on HRQoL became significant in our sensitivity analysis when two studies conducted during adjuvant chemotherapy [SMD = 0.30 (95% CI 0.04-0.55), I2 = 37.0%] were excluded. These data indicate that PRT improves physical functioning and reduces the risk of BCRL. Clinical practice guidelines should be updated to inform clinicians on the benefits of PRT in this cohort.