<p> Maternal high fat (HF) intake before and/or during pregnancy increases female offsprings&rsquo; mammary cancer risk in several preclinical models. Here I studied if maternal HF intake during pregnancy cause transgenerational increase in mammary cancer risk, and if the increase is reversible by treating adult offspring with inhibitors of histone deacetylases (HDAC) or DNA methyltransferases (DNMT).</p><p> Pregnant C57BL/6NTac mice were fed either a diet high in n-6 polyunsaturated fatty acids (HF) or control diet (CON). HF diet was given from gestational day (GD) 10 &ndash; 20 to target fetal primordial germ cell formation and differentiation to germ cells. Offspring in subsequent F1-F3 generations were only fed CON diet. Mammary tumor incidence, induced by 7,12-dimethylbenz[a]anthracene (DMBA), was significantly higher in F1 and F3 HF offspring, than in the controls. Tumor latency was shorter and burden higher in F1 HF, with similar trends, though not statistically significant, in F3 HF.</p><p> RNA-sequencing of normal mammary glands revealed 1587 and 4423 differentially expressed genes between HF and CON offspring in F1 and F3, respectively, of which 48 genes were similarly altered in both generations. Ingenuity Pathway Analysis identified genes associated with Notch signaling as key alterations in HF mammary glands. Knowledge-fused Differential Dependency Network analysis identified 10 node genes in HF offspring uniquely connected to genes linked to increased cancer risk, therapy resistance, poor prognosis, and impaired anti-cancer immunity.</p><p> Next, I studied whether HDAC and DNMT inhibitor treatment in adulthood of the offspring, prior to tumor formation, could reverse the increased mammary cancer risk caused by <i>in utero</i> HF exposure. CON and HF offspring were given valproic acid and hydralazine in drinking water (epi-treatment), starting one week after tumor initiation by DMBA. Epi-treatment significantly decreased tumor burden in HF offspring, potentially through reactivation of silenced tumor suppressors <i>CLCA1</i> and <i>CDKN2A</i>, but adversely affected CON offspring. These adverse effects were linked to upregulation of PERK, p62 and HIF-1&alpha; in CON.</p><p> In summary, maternal HF intake during pregnancy induced transgenerational increase in offsprings&rsquo; mammary cancer risk, causes persistent changes in the expression of genes linked to increased breast cancer risk, and epi-treatment in adulthood may reduce this risk.</p>

<p> The purpose of this study was to determine the taste function of post-laryngectomy head and neck cancer survivors and examine associations with dietary intake and malnutrition status. In this randomized, double-blinded, controlled trial, participants were tested in their ability to identify solutions of the five basic tastes of bitter, salty, sour, sweet, and umami. A 24-hour dietary recall was conducted to determine dietary intake and participants were screened for positive markers of malnutrition. At low concentration, 33.3% of participants were able to identify bitter, 16.7% salty, 16.7% sour, 0% sweet, and 0% umami. There were no reported positive features of malnutrition though a majority of participants&rsquo; 24-hour dietary recall showed energy intake below recommendation. Positive correlations were found between energy intake and correct identification scores for sour at medium (<i>r</i> = 0.956, <i>p</i> = 0.003) and low (<i>r</i> = 0.912, <i> p</i> = 0.011) concentrations and umami at low concentration (<i> r</i> = 0.854, <i>p</i> = 0.031). Findings suggest that taste impairment is a long-term post-treatment effect in post-laryngectomy head and neck cancer survivors though adaptation seems to occur. These findings promote the need for preventative or rehabilitative interventions for taste impairment to prevent subsequent alterations in dietary intake and maximize quality of life.</p><p>

<p> Diet is a modifiable risk factor that strongly influences colorectal cancer (CRC) risk. Previous studies have associated CRC with impaired nutrient intakes including calcium, selenium and folate intakes. This study sought to investigate relationships between calcium, selenium and folate intakes and CRC. Calcium, selenium, and folate intakes and incidence of CRC from a selected cohort within the National Health and Nutrition Examination Survey (NHANES) 1999&ndash;2014 were analyzed. A total of 2,130 men and women aged 31 to 85 with and without CRC were included in the analysis. The relationships between daily intakes of calcium, selenium and folate and CRC incidence were analyzed using &chi;² test and logistic regression. Correlations between calcium, selenium and folate intakes and CRC were also assessed using Pearson&rsquo;s correlation coefficient.</p>

There are no practical options to reduce breast cancer risk in American women that are without side-effects. Almost all preventive strategies are designed to diminish the role of estrogens in promoting breast cell proliferation. Brassica vegetables (e.g., broccoli) contain indole glucosinolates that can shift estrogen metabolism away from the highly estrogenic 16α-hydroxyestrone (16HE) and toward 2-hydroxyestrone (2HE), which has little estrogenic activity on breast cells. The relative strength of these two pathways is measured in urine as the ratio 2HE/16HE (2/16). In controlled trials that have enrolled premenopausal women or young men, large quantities of Brassica vegetables or indole glucosinolate derivatives decreased urinary 16HE levels relative to 2HE levels, possibly lowering breast cancer risk. However, in order to be an acceptable and effective preventative, Brassica vegetables must shift estrogen metabolism as Brassica consumption is practiced within free-living women. The goal of this research is to determine if Brassica should be further explored as a strategy to prevent breast cancer. In order to do so, it was determined that three issues must be addressed: (1) Brassica consumption must increase the 2/16 ratio among healthy free-living women, without serious side-affects, (2) the 2/16 ratio must be a valid indicator of breast cancer risk, and (3) a reliable and valid method to estimate Brassica consumption must be identified. As part of this research, thirty-seven healthy postmenopausal women participated in a dietary intervention designed to facilitate daily Brassica consumption. The diet, 2/16, and other information were measured before, during, and after the intervention. The 2/16 ratio significantly increased with greater Brassica intake. However, urinary 2/16 levels between participants were sensitive to dietary fat and fiber intake, and future studies evaluating the 2/16-breast cancer association should control for macronutrient intake. Dithiocarbamate excretion, a biomarker of Brassica consumption, inconsistently predicted self-reported Brassica intake and is sensitive to the types of vegetables consumed. However, DTC may be useful to rank-order participants in epidemiological studies. Overall, to the extent that lower 2/16 values are associated with increased breast cancer risk, Brassica vegetables may be an important component of any strategy to reduce breast cancer risk.