Low-linoleic acid diet and oestrogen enhance the conversion of α-linolenic acid into DHA through modification of conversion enzymes and transcription factors.

Conversion of α-linolenic acid (ALA) into the longer chain n-3 PUFA has been suggested to be affected by the dietary intake of linoleic acid (LA), but the mechanism is not well known. Therefore, the purpose of this study was to evaluate the effect of a low-LA diet with and without oestrogen on the fatty acid conversion enzymes and transcription factors. Rats were fed a modified American Institute of Nutrition-93G diet with 0% n-3 PUFA or ALA, containing low or high amounts of LA for 12 weeks. At 8 weeks, the rats were injected with maize oil with or without 17ß-oestradiol-3-benzoate (E) at constant intervals for the remaining 3 weeks. Both the low-LA diet and E significantly increased the hepatic expressions of PPAR-α, fatty acid desaturase (FADS) 2, elongase of very long chain fatty acids 2 (ELOVL2) and ELOVL5 but decreased sterol regulatory element binding protein 1. The low-LA diet, but not E, increased the hepatic expression of FADS1, and E increased the hepatic expression of oestrogen receptor-α and ß. The low-LA diet and E had synergic effects on serum and liver levels of DHA and on the hepatic expression of PPAR-α. In conclusion, the low-LA diet and oestrogen increased the conversion of ALA into DHA by upregulating the elongases and desaturases of fatty acids through regulating the expression of transcription factors. The low-LA diet and E had a synergic effect on serum and liver levels of DHA through increasing the expression of PPAR-α.

Glucosinolate and isothiocyanate intakes are inversely associated with breast cancer risk: a case-control study in China.

Although previous studies have investigated the association of cruciferous vegetable consumption with breast cancer risk, few studies focused on the association between bioactive components in cruciferous vegetables, glucosinolates (GSL) and isothiocyanates (ITC), and breast cancer risk. This study aimed to examine the association between consumption of cruciferous vegetables and breast cancer risk according to GSL and ITC contents in a Chinese population. A total of 1485 cases and 1506 controls were recruited into this case-control study from June 2007 to March 2017. Consumption of cruciferous vegetables was assessed using a validated FFQ. Dietary GSL and ITC were computed by using two food composition databases linking GSL and ITC contents in cruciferous vegetables with responses to the FFQ. The OR and 95 % CI were assessed by unconditional logistic regression after adjusting for the potential confounders. Significant inverse associations were found between consumption of cruciferous vegetables, GSL and ITC and breast cancer risk. The adjusted OR comparing the highest with the lowest quartile were 0·51 (95 % CI 0·41, 0·63) for cruciferous vegetables, 0·54 (95 % CI 0·44, 0·67) for GSL and 0·62 (95 % CI 0·50, 0·76) for ITC, respectively. These inverse associations were also observed in both premenopausal and postmenopausal women. Subgroup analysis by hormone receptor status found inverse associations between cruciferous vegetables, GSL and ITC and both hormone-receptor-positive or hormone-receptor-negative breast cancer. This study indicated that consumption of cruciferous vegetables, GSL and ITC was inversely associated with breast cancer risk among Chinese women.

Dietary inflammatory index before diagnosis and survival in an Italian cohort of women with breast cancer.

The dietary inflammatory indexTM (DII) has been shown to correlate with concentrations of several inflammatory markers and a variety of chronic disease endpoints, including cancers of various anatomic sites. We investigated whether the DII was associated with the risk for death among women with breast cancer (BrCa). This retrospective cohort study included 1453 women with BrCa, diagnosed between 1990 and 1994, and previously enrolled in a case-control study in northern Italy. With a median follow-up of 12·6 years, we observed 503 deaths, among which 398 were due to BrCa. The usual diet was assessed at BrCa diagnosis using a validated FFQ. DII scores were calculated using thirty-one foods/nutrients. Hazard ratios (HR) of death from all causes or from BrCa, with corresponding 95 % CI, were calculated using the Cox models, adjusted for age at diagnosis, tumour stage, oestrogen/progesterone receptor status and other potential confounders. The median DII score of the study women was -1·23, with a relatively narrow range (interquartile range -2·24 to -0·11), indicating a mainly anti-inflammatory diet. There was no difference in survival according to DII tertiles, neither considering all-cause mortality (HRtertile III v. I 1·00; 95 % CI 0·78, 1·28) nor BrCa-specific mortality (HRtertile III v. I 0·97; 95 % CI 0·73, 1·27). Study findings did not suggest an association between the inflammatory potential of diet, measured by the DII, and the survival of BrCa women. However, further studies are needed in populations reporting higher DII scores and a broader range of variability in the scores.

A higher Dietary Inflammatory Index score is associated with a higher risk of breast cancer among Chinese women: a case-control study.

Previous studies have investigated the association between dietary inflammatory potential and the development of cancer. For breast cancer the results have been equivocal. The present study aimed to investigate whether higher Dietary Inflammatory IndexTM (DII) scores were associated with increased risk of breast cancer among Chinese women. A total of 867 cases and 824 controls were recruited into the present case-control study from September 2011 to February 2016. DII scores were computed based on baseline dietary intake assessed by a validated 81-item FFQ. The OR and 95 % CI were assessed by multivariable logistic regression after adjusting for various potential confounders. DII scores in this study ranged from -5·87 (most anti-inflammatory score) to +5·71 (most proinflammatory score). A higher DII score was associated with a higher breast cancer risk (adjusted ORquartile 4 v. 1 2·28; 95 % CI 1·71, 3·03; adjusted ORcontinuous 1·40; 95 %CI 1·25, 1·39). In stratified analyses, positive associations also were observed except for underweight women or women with either oestrogen receptor+ or progesterone receptor+ status (but not both). Results from this study indicated that higher DII scores, corresponding to more proinflammatory diets, were positively associated with breast cancer risk among Chinese women.

Perinatal maternal high-fat diet induces early obesity and sex-specific alterations of the endocannabinoid system in white and brown adipose tissue of weanling rat offspring.

Perinatal maternal high-fat (HF) diet programmes offspring obesity. Obesity is associated with overactivation of the endocannabinoid system (ECS) in adult subjects, but the role of the ECS in the developmental origins of obesity is mostly unknown. The ECS consists of endocannabinoids, cannabinoid receptors (cannabinoid type-1 receptor (CB1) and cannabinoid type-2 receptor (CB2)) and metabolising enzymes. We hypothesised that perinatal maternal HF diet would alter the ECS in a sex-dependent manner in white and brown adipose tissue of rat offspring at weaning in parallel to obesity development. Female rats received standard diet (9 % energy content from fat) or HF diet (29 % energy content from fat) before mating, during pregnancy and lactation. At weaning, male and female offspring were killed for tissue harvest. Maternal HF diet induced early obesity, white adipocyte hypertrophy and increased lipid accumulation in brown adipose tissue associated with sex-specific changes of the ECS's components in weanling rats. In male pups, maternal HF diet decreased CB1 and CB2 protein in subcutaneous adipose tissue. In female pups, maternal HF diet increased visceral and decreased subcutaneous CB1. In brown adipose tissue, maternal HF diet increased CB1 regardless of pup sex. In addition, maternal HF diet differentially changed oestrogen receptor across the adipose depots in male and female pups. The ECS and oestrogen signalling play an important role in lipogenesis, adipogenesis and thermogenesis, and we observed early changes in their targets in adipose depots of the offspring. The present findings provide insights into the involvement of the ECS in the developmental origins of metabolic disease induced by inadequate maternal nutrition in early life.

An update on diet and nutritional factors in systemic lupus erythematosus management.

Systemic lupus erythematosus (SLE) is a chronic inflammatory and autoimmune disease characterised by multiple organ involvement and a large number of complications. SLE management remains complicated owing to the biological heterogeneity between patients and the lack of safe and specific targeted therapies. There is evidence that dietary factors can contribute to the geoepidemiology of autoimmune diseases such as SLE. Thus, diet therapy could be a promising approach in SLE owing to both its potential prophylactic effects, without the side effects of classical pharmacology, and its contribution to reducing co-morbidities and improving quality of life in patients with SLE. However, the question arises as to whether nutrients could ameliorate or exacerbate SLE and how they could modulate inflammation and immune function at a molecular level. The present review summarises preclinical and clinical experiences to provide the reader with an update of the positive and negative aspects of macro- and micronutrients and other nutritional factors, including dietary phenols, on SLE, focusing on the mechanisms of action involved.

Calcium intake and breast cancer risk: meta-analysis of prospective cohort studies.

Findings from observational studies have suggested a possible relation between Ca and breast cancer risk. However, the results of these studies are inconclusive, and the dose-response relationship between Ca intake and risk of breast cancer remains to be determined. A meta-analysis of prospective studies was conducted to address these issues. PubMed and Embase databases were searched for relevant studies concerning the association between Ca intake and breast cancer up to March 2016. The summary relative risks (RR) with 95 % CI were calculated with a random-effects model. The final analysis included eleven prospective cohort studies involving 26 606 cases and 872 895 participants. The overall RR of breast cancer for high v. low intake of Ca was 0·92 (95 % CI 0·85, 0·99), with moderate heterogeneity (P=0·026, I 2=44·2 %). In the subgroup analysis, the inverse association appeared stronger for premenopausal breast cancer (RR 0·75; 95 % CI 0·59, 0·96) than for postmenopausal breast cancer (RR 0·94; 95 % CI 0·87, 1·01). Dose-response analysis revealed that each 300 mg/d increase in Ca intake was associated with 2 % (RR 0·98; 95 % CI 0·96, 0·99), 8 % (RR 0·92; 95 % CI 0·87, 0·98) and 2 % (RR 0·98; 95 % CI 0·97, 0·99) reduction in the risk of total, premenopausal and postmenopausal breast cancer, respectively. Our findings suggest an inverse dose-response association between Ca intake and risk of breast cancer.

Dietary pattern and breast cancer risk in Japanese women: the Japan Public Health Center-based Prospective Study (JPHC Study).

Evidence that diet is associated with breast cancer risk is inconsistent. Most of the studies have focused on risks associated with specific foods and nutrients, rather than overall diet. In this study, we aimed to evaluate the association between dietary patterns and breast cancer risk in Japanese women. A total of 49 552 Japanese women were followed-up from 1995 to 1998 (5-year follow-up survey) until the end of 2012 for an average of 14·6 years. During 725 534 person-years of follow-up, 718 cases of breast cancer were identified. We identified three dietary patterns (prudent, westernised and traditional Japanese). The westernised dietary pattern was associated with a 32 % increase in breast cancer risk (hazard ratios (HR) 1·32; 95 % CI 1·03, 1·70; P trend=0·04). In particular, subjects with extreme intake of the westernised diet (quintile (Q) Q5_5th) had an 83 % increase in risk of breast cancer in contrast to those in the lowest Q1 (HR 1·83; 95 % CI 1·25, 2·68; P trend=0·01). In analyses stratified by menopausal status, postmenopausal subjects in the highest quintile of the westernised dietary pattern had a 29 % increased risk of breast cancer (HR 1·29; 95 % CI 0·99, 1·76; P trend=0·04). With regard to hormone receptor status, the westernised dietary pattern was associated with an increased risk of oestrogen receptor-positive/progesterone receptor-positivetumours (HR 2·49; 95 % CI 1·40, 4·43; P trend<0·01). The other dietary patterns were not associated with the risk of breast cancer in Japanese women. A westernised dietary pattern is associated with an increased risk of breast cancer in Japanese women.

Specific serum carotenoids are inversely associated with breast cancer risk among Chinese women: a case-control study.

Previous epidemiological studies have revealed the anti-cancer effect of dietary circulating carotenoids. However, the protective role of specific individual circulating carotenoids has not been elucidated. The purpose of this study was to examine whether serum carotenoids, including α-carotene, ß-carotene, ß-cryptoxanthin, lycopene and lutein/zeaxanthin, could lower the risk for breast cancer among Chinese women. A total of 521 women with breast cancer and age-matched controls (5-year interval) were selected from three teaching hospitals in Guangzhou, China. Concentrations of α-carotene, ß-carotene, ß-cryptoxanthin, lycopene and lutein/zeaxanthin were measured using HPLC. Unconditional logistic regression models were used to calculate OR and 95% CI using quartiles defined in the control subjects. Significant inverse associations were observed between serum α-carotene, ß-carotene, lycopene, lutein/zeaxanthin and the risk for breast cancer. The multivariate OR for the highest quartile of serum concentration compared with the lowest quartile were 0·44 (95% CI 0·30, 0·65) for α-carotene, 0·27 (95% CI 0·18, 0·40) for ß-carotene, 0·41 (95% CI 0·28, 0·61) for lycopene and 0·26 (95% CI 0·17, 0·38) for lutein/zeaxanthin. However, no significant association was found between serum ß-cryptoxanthin and the risk for breast cancer. Stratified analysis by menopausal status and oestrogen receptor (ER)/progesterone receptor (PR) showed that serum α-carotene, ß-carotene, lycopene and lutein/zeaxanthin were inversely associated with breast cancer risk among premenopausal women and among all subtypes of ER or PR status. The results suggest a protective role of α-carotene, ß-carotene, lycopene and lutein/zeaxanthin, but not ß-cryptoxanthin, in breast cancer risk.

Vegetarian dietary patterns and the risk of breast cancer in a low-risk population.

Among cancers in American women, breast cancer (BC) has the second highest incidence and mortality. The association of BC with diet has been inconsistent. Studies that evaluate associations with dietary patterns are less common and reflect an individual's whole diet. We associated dietary patterns with the risk of BC in American women of the Adventist Health Study-2 (AHS-2), a prospective cohort of 96 001 subjects recruited between 2002 and 2007. Answers to a previously validated FFQ were used to classify subjects to vegan, lacto-ovo-vegetarian, pesco-vegetarian, semi-vegetarian and non-vegetarian dietary patterns. Incident BC were identified by matching AHS-2 subjects to data from forty-eight state cancer registries. Statistical analyses used proportional hazard regression analyses with covariates that were chosen a priori. From 50 404 female participants (26 193 vegetarians), we identified 892 incident BC cases, with 478 cases among vegetarians. As compared with non-vegetarians, all vegetarians combined did not have a significantly lower risk (hazard ratio (HR) 0·97; CI 0·84, 1·11; P=0·64). However, vegans showed consistently lower (but non-significant) point estimates when compared with non-vegetarians (all cases: HR 0·78; CI 0·58, 1·05; P=0·09). In summary, participants in this cohort who follow a vegetarian dietary pattern did not experience a lower risk of BC as compared with non-vegetarians, although lower risk in vegans is possible. These findings add to the very limited literature associating vegetarian diets with BC risk and can assist nutritionists when evaluating the impact of these diets. The findings will also motivate further evaluation of vegan diets and their special characteristics.

Dietary and pharmacological compounds altering intestinal calcium absorption in humans and animals.

The intestine is the only gate for the entry of Ca to the body in humans and mammals. The entrance of Ca occurs via paracellular and intracellular pathways. All steps of the latter pathway are regulated by calcitriol and by other hormones. Dietary and pharmacological compounds also modulate the intestinal Ca absorption process. Among them, dietary Ca and P are known to alter the lipid and protein composition of the brush-border and basolateral membranes and, consequently, Ca transport. Ca intakes are below the requirements recommended by health professionals in most countries, triggering important health problems. Chronic low Ca intake has been related to illness conditions such as osteoporosis, hypertension, renal lithiasis and incidences of human cancer. Carbohydrates, mainly lactose, and prebiotics have been described as positive modulators of intestinal Ca absorption. Apparently, high meat proteins increase intestinal Ca absorption while the effect of dietary lipids remains unclear. Pharmacological compounds such as menadione, dl-butionine-S,R-sulfoximine and ursodeoxycholic acid also modify intestinal Ca absorption as a consequence of altering the redox state of the epithelial cells. The paracellular pathway of intestinal Ca absorption is poorly known and is under present study in some laboratories. Another field that needs to be explored more intensively is the influence of the gene × diet interaction on intestinal Ca absorption. Health professionals should be aware of this knowledge in order to develop nutritional or medical strategies to stimulate the efficiency of intestinal Ca absorption and to prevent diseases.

Machine learning assisted analysis of breast cancer gene expression profiles reveals novel potential prognostic biomarkers for triple-negative breast cancer.

Tumor heterogeneity and the unclear metastasis mechanisms are the leading cause for the unavailability of effective targeted therapy for Triple-negative breast cancer (TNBC), a breast cancer (BrCa) subtype characterized by high mortality and high frequency of distant metastasis cases. The identification of prognostic biomarker can improve prognosis and personalized treatment regimes. Herein, we collected gene expression datasets representing TNBC and Non-TNBC BrCa. From the complete dataset, a subset reflecting solely known cancer driver genes was also constructed. Recursive Feature Elimination (RFE) was employed to identify top 20, 25, 30, 35, 40, 45, and 50 gene signatures that differentiate TNBC from the other BrCa subtypes. Five machine learning algorithms were employed on these selected features and on the basis of model performance evaluation, it was found that for the complete and driver dataset, XGBoost performs the best for a subset of 25 and 20 genes, respectively. Out of these 45 genes from the two datasets, 34 genes were found to be differentially regulated. The Kaplan-Meier (KM) analysis for Distant Metastasis Free Survival (DMFS) of these 34 differentially regulated genes revealed four genes, out of which two are novel that could be potential prognostic genes (POU2AF1 and S100B). Finally, interactome and pathway enrichment analyses were carried out to investigate the functional role of the identified potential prognostic genes in TNBC. These genes are associated with MAPK, PI3-AkT, Wnt, TGF-ß, and other signal transduction pathways, pivotal in metastasis cascade. These gene signatures can provide novel molecular-level insights into metastasis.

Vitamin D deficiency in the pathogenesis of leiomyoma and intravascular leiomyomatosis: A case report and review of the literature.

This is a case of recurrent intravascular leiomyomatosis in a pre-menopausal woman of African-Caribbean heritage. She presented in 2006 with multiple uterine leiomyomata, tumour invading the inferior vena cava (IVC) extending into the right atrium, and pulmonary metastases. Her initial presentation was treated surgically. On recurrence she was treated by oestrogen suppression using a combination of goserelin and letrozole, with a substantial response. She subsequently reported further regression of disease following exposure to strong sunlight enabling her to discontinue oestrogen suppression without relapse. The hypothesis is that the benefit was due to vitamin D. The role of hypovitaminosis D in the pathogenesis of uterine leiomyomata is discussed, including epidemiology data demonstrating a link between ethnicity and risk and the proven mechanisms by which vitamin D controls oestrogen and progesterone receptor expression and influences other signalling pathways involved in the pathogenesis of leiomyomas. Data indicating the intermediate malignancy nature of intravascular leiomyomatosis, are discussed. We are not aware of other reports indicating a link between intravascular leiomyomatosis and a lack of vitamin D.

Diet, menopause and the risk of ovarian, endometrial and breast cancer.

Menopause, the permanent cessation of the menstrual cycle, marks the end of a woman's reproductive lifespan. In addition to changes in sex hormone levels associated with menopause, its timing is another predictor of future health outcomes such as duration of the presence of vasomotor symptoms (VMS) and the risk of hormone-related cancers. With ageing of the population, it is estimated that worldwide 1·2 billion women will be menopausal by the year 2030. Previously the effects of reproductive factors (e.g. parity, age at menarche, pregnancy) and socio-demographic factors on intermediate and long-term health outcomes of menopause have been widely documented. However, little is known about whether diet could have an impact on these. Therefore, we review current evidence on the associations of diet with menopause, presence of VMS and the risk of hormone-related cancers such as ovarian, endometrial and breast cancer. Dietary factors could influence the lifespan of the ovaries and sex-hormones levels, hence the timing of natural menopause. Few studies reported an association between diet, in particular soya consumption, and a reduced risk of VMS. Sustained oestrogen exposure has been associated with a higher risk of hormone-related cancers and thus high-fat and meat diets have been linked with an increased risk of these cancers. However, to better understand the mechanistic pathways involved and to make stronger conclusions for these relationships, further studies investigating the associations of dietary intakes and dietary patterns with menopause, presence of VMS and the risk of hormone-related cancers are required.

Early breast cancer: why does obesity affect prognosis?

High BMI is associated with an increased risk of breast cancer in post-menopausal women but poorer outcomes in all age groups. The underlying mechanism is likely to be multi-factorial. Patients with a high BMI may present later due to body habitus. Some studies have also indicated an increased incidence of biologically adverse features, including a higher frequency of oestrogen receptor (ER negative) tumours, in obese patients. Obese patients have a higher frequency of surgical complications, potentially delaying systemic therapies, and reports suggest that chemotherapy and endocrine therapy are less effective in patients with BMI ≥30 kg/m2.High BMI is generally interpreted as excess adiposity and a World Cancer Research Fund report judged that the associations between BMI and incidence of breast cancer were due to body fatness. However, BMI cannot distinguish lean mass from fat mass, or characterise body fat distribution. Most chemotherapy drugs are dosed according to calculated body surface area (BSA). Patients with a similar BSA or BMI may have wide variations in their distribution of adipose tissue and skeletal muscle (body composition); however, few studies have looked at the effect of this on chemotherapy tolerance or effectiveness. Finally, adjuvant treatments for breast cancer can themselves result in body composition changes.Research is required to fully understand the biological mechanisms by which obesity influences cancer behaviour and the impact of obesity on treatment effectiveness and tolerance so that specific management strategies can be developed to improve the prognosis of this patient group.

Endocrine disruption by dietary phyto-oestrogens: impact on dimorphic sexual systems and behaviours.

A wide range of health benefits have been ascribed to soya intake including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms. Because it is a hormonally active diet, however, soya can also be endocrine disrupting, suggesting that intake has the potential to cause adverse health effects in certain circumstances, particularly when exposure occurs during development. Consequently, the question of whether or not soya phyto-oestrogens are beneficial or harmful to human health is neither straightforward nor universally applicable to all groups. Possible benefits and risks depend on age, health status, and even the presence or absence of specific gut microflora. As global consumption increases, greater awareness and consideration of the endocrine-disrupting properties of soya by nutrition specialists and other health practitioners is needed. Consumption by infants and small children is of particular concern because their hormone-sensitive organs, including the brain and reproductive system, are still undergoing sexual differentiation and maturation. Thus, their susceptibility to the endocrine-disrupting activities of soya phyto-oestrogens may be especially high. As oestrogen receptor partial agonists with molecular and cellular properties similar to anthropogenic endocrine disruptors such as bisphenol A, the soya phyto-oestrogens provide an interesting model for how attitudes about what is 'synthetic' v. what is 'natural,' shapes understanding and perception of what it means for a compound to be endocrine disrupting and/or potentially harmful. This review describes the endocrine-disrupting properties of soya phyto-oestrogens with a focus on neuroendocrine development and behaviour.

Primary surgical treatment of locally advanced breast cancer in low resource settings.

•Optimum management of locally advanced breast cancer is multidisciplinary.•Neoadjuvant chemotherapy is mainstay of management.•Primary surgical treatment may be acceptable in selected patients.