Estimated intake of dietary phyto-oestrogens in Australian women and evaluation of correlates of phyto-oestrogen intake.

The role of dietary phyto-oestrogens in health has been of continued interest and debate, but data available on the distribution of intake in the Australian diet are scarce. Therefore, we aimed to estimate phyto-oestrogen consumption in Australian women, describe the pattern of intake and identify correlates of high phyto-oestrogen intake. Study participants were 2078 control women (18-79 years) from two population-based case-control studies on gynaecological cancers (2002-2007). Dietary information was obtained using a 135-item FFQ, and the intakes of isoflavones, lignans, enterolignans and coumestans, including their individual components, were estimated using a database of phyto-oestrogen content in food developed in the UK. Median total intake (energy-adjusted) of phyto-oestrogens was 1·29 mg/d, including 611 µg/d isoflavones, 639 µg/d lignans, 21 µg/d enterolignans and 8 µg/d coumestrol. Both isoflavone and lignan intakes were strongly skewed towards higher values and positively correlated with age. Women consumed on average two servings of soyabean foods/week. Compared to lower phyto-oestrogen consumers (≤1·29 mg/d, median split), higher phyto-oestrogen consumers (>1·29 mg/d) were slightly older, less likely to be smokers, had a higher educational and physical activity level, lower BMI, lower intake of dietary fat, and higher intake of fibre, selected micronutrients and soyabean foods (all P < 0·03). The daily intake of phyto-oestrogens in Australian women with predominantly Caucasian ethnicity is approximately 1 mg; this is similar to other Western populations, but considerably lower than that among Asian women. However, those with a relatively high phyto-oestrogen diet seem to have a healthier lifestyle and a more favourable dietary profile compared to others

A system for success: BMC Systems Biology, a new open access journal

BMC Systems Biology is the first open access journal spanning the growing field of systems biology from molecules up to ecosystems. The journal has launched as more and more institutes are founded that are similarly dedicated to this new approach. BMC Systems Biology builds on the ongoing success of the BMC series, providing a venue for all sound research in the systems-level analysis of biology

The Investigation into CYP2E1 in Relation to the Level of Response to Alcohol Through a Combination of Linkage and Association Analysis: CYP2E1 AND THE RESPONSE TO ALCOHOL

A low level of response to alcohol during an individual’s early experience with alcohol is associated with an increase risk for alcoholism. A family-based genome-wide linkage analysis using sibling pairs that underwent an alcohol challenge where the level of response to alcohol was measured with the Subjective High Assessment Scale (SHAS) implicated the 10q terminal region. CYP2E1, a gene known for its involvement with ethanol metabolism, maps to this region

Refocusing multiple stressor research around the targets and scales of ecological impacts

Ecological communities face a variety of environmental and anthropogenic stressors acting simultaneously. Stressor impacts can combine additively or can interact, causing synergistic or antagonistic effects. Our knowledge of when and how interactions arise is limited, as most models and experiments only consider the effect of a small number of non-interacting stressors at one or few scales of ecological organization. This is concerning because it could lead to significant underestimations or overestimations of threats to biodiversity. Furthermore, stressors have been largely classified by their source rather than by the mechanisms and ecological scales at which they act (the target). Here, we argue, first, that a more nuanced classification of stressors by target and ecological scale can generate valuable new insights and hypotheses about stressor interactions. Second, that the predictability of multiple stressor effects, and consistent patterns in their impacts, can be evaluated by examining the distribution of stressor effects across targets and ecological scales. Third, that a variety of existing mechanistic and statistical modelling tools can play an important role in our framework and advance multiple stressor research

ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas

&lt;b&gt;Objective&lt;/b&gt; &lt;i&gt;ABCB1&lt;/i&gt; encodes the multi-drug efflux pump P-glycoprotein (P-gp) and has been implicated in multi-drug resistance. We comprehensively evaluated this gene and flanking regions for an association with clinical outcome in epithelial ovarian cancer (EOC).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; The best candidates from fine-mapping analysis of 21 &lt;i&gt;ABCB1&lt;/i&gt; SNPs tagging C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642) were analysed in 4616 European invasive EOC patients from thirteen Ovarian Cancer Association Consortium (OCAC) studies and The Cancer Genome Atlas (TCGA). Additionally we analysed 1,562 imputed SNPs around ABCB1 in patients receiving cytoreductive surgery and either ‘standard’ first-line paclitaxel–carboplatin chemotherapy (n = 1158) or any first-line chemotherapy regimen (n = 2867). We also evaluated ABCB1 expression in primary tumours from 143 EOC patients.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Result&lt;/b&gt; Fine-mapping revealed that rs1128503, rs2032582, and rs1045642 were the best candidates in optimally debulked patients. However, we observed no significant association between any SNP and either progression-free survival or overall survival in analysis of data from 14 studies. There was a marginal association between rs1128503 and overall survival in patients with nil residual disease (HR 0.88, 95% CI 0.77–1.01; p = 0.07). In contrast, &lt;i&gt;ABCB1&lt;/i&gt; expression in the primary tumour may confer worse prognosis in patients with sub-optimally debulked tumours.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt; Our study represents the largest analysis of &lt;i&gt;ABCB1&lt;/i&gt; SNPs and EOC progression and survival to date, but has not identified additional signals, or validated reported associations with progression-free survival for rs1128503, rs2032582, and rs1045642. However, we cannot rule out the possibility of a subtle effect of rs1128503, or other SNPs linked to it, on overall survival.&lt;p&gt;&lt;/p&gt

Clinical, biochemical, and genetic features associated with VARS2-related mitochondrial disease

In recent years, an increasing number of mitochondrial disorders have been associated with mutations in mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs), which are key enzymes of mitochondrial protein synthesis. Bi-allelic functional variants in VARS2, encoding the mitochondrial valyl tRNA-synthetase, were first reported in a patient with psychomotor delay and epilepsia partialis continua associated with an oxidative phosphorylation (OXPHOS) Complex I defect, before being described in a patient with a neonatal form of encephalocardiomyopathy. Here we provide a detailed genetic, clinical, and biochemical description of 13 patients, from nine unrelated families, harboring VARS2 mutations. All patients except one, who manifested with a less severe disease course, presented at birth exhibiting severe encephalomyopathy and cardiomyopathy. Features included hypotonia, psychomotor delay, seizures, feeding difficulty, abnormal cranial MRI, and elevated lactate. The biochemical phenotype comprised a combined Complex I and Complex IV OXPHOS defect in muscle, with patient fibroblasts displaying normal OXPHOS activity. Homology modeling supported the pathogenicity of VARS2 missense variants. The detailed description of this cohort further delineates our understanding of the clinical presentation associated with pathogenic VARS2 variants and we recommend that this gene should be considered in early-onset mitochondrial encephalomyopathies or encephalocardiomyopathies.Peer reviewe

Offspring sex and risk of epithelial ovarian cancer: a multinational pooled analysis of 12 case-control studies

While childbearing protects against risk of epithelial ovarian cancer (EOC), few studies have explored the impact on maternal EOC risk of sex of offspring, which may affect the maternal environment during pregnancy. We performed a pooled analysis among parous participants from 12 case–controls studies comprising 6872 EOC patients and 9101 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable logistic regression for case–control associations and polytomous logistic regression for histotype-specific associations, all adjusted for potential confounders. In general, no associations were found between offspring sex and EOC risk. However, compared to bearing only female offspring, bearing one or more male offspring was associated with increased risk of mucinous EOC (OR = 1.45; 95% CI = 1.01-2.07), which appeared to be limited to women reporting menarche before age 13 compared to later menarche (OR = 1.71 vs 0.99; P-interaction = 0.02). Bearing increasing numbers of male offspring was associated with greater risks of mucinous tumors (OR = 1.31, 1.84, 2.31, for 1, 2 and 3 or more male offspring, respectively; trend-p = 0.005). Stratifying by hormonally-associated conditions suggested that compared to bearing all female offspring, bearing a male offspring was associated with lower risk of endometrioid cancer among women with a history of adult acne, hirsutism, or polycystic ovary syndrome (OR = 0.49, 95% CI = 0.28-0.83) but with higher risk among women without any of those conditions (OR = 1.64 95% CI = 1.14–2.34; P-interaction = 0.003). Offspring sex influences the childbearing-EOC risk relationship for specific histotypes and conditions. These findings support the differing etiologic origins of EOC histotypes and highlight the importance of EOC histotype-specific epidemiologic studies. These findings also suggest the need to better understand how pregnancy affects EOC ris

Association of Frequent Aspirin Use With Ovarian Cancer Risk According to Genetic Susceptibility

IMPORTANCE: Frequent aspirin use is associated with reduced ovarian cancer risk, but it is unknown whether genetic factors modify this association. Understanding effect modifiers is important given that any use of aspirin for ovarian cancer chemoprevention will likely need to focus on specific higher-risk subgroups. OBJECTIVE: To evaluate whether the association between frequent aspirin use and ovarian cancer is modified by a polygenic score (PGS) for nonmucinous ovarian cancer. DESIGN, SETTING, AND PARTICIPANTS: We pooled individual-level data from 8 population-based case-control studies from the Ovarian Cancer Association Consortium conducted in the US, UK, and Australia between 1995 and 2009. We included case patients and control participants with both genetic data and data on frequent aspirin use. Case patients with mucinous ovarian cancer were excluded. Data were analyzed between November 1, 2021, and July 31, 2022. EXPOSURES: Frequent aspirin use, defined as daily or almost daily use for 6 months or longer. MAIN OUTCOMES AND MEASURES: The main outcome was nonmucinous epithelial ovarian cancer. We used logistic regression to estimate odds ratios (ORs) and 95% CIs and likelihood ratio tests to investigate effect modification by the PGS. RESULTS: There were 4476 case patients with nonmucinous ovarian cancer and 6659 control participants included in this analysis. At study enrollment, the median (IQR) age was 58 (50-66) years for case patients and 57 (49-65) years for control participants. Case patients and control participants self-reported that they were Black (122 [3%] vs 218 [3%]), White (3995 [89%] vs 5851 [88%]), or of other race and ethnicity (348 [8%] vs 580 [9%]; race and ethnicity were unknown for 11 [0%] vs 10 [0%]). There were 575 case patients (13%) and 1030 control participants (15%) who reported frequent aspirin use. The 13% reduction in ovarian cancer risk associated with frequent aspirin use (OR, 0.87 [95% CI, 0.76-0.99]) was not modified by the PGS. Consistent ORs were observed among individuals with a PGS less than (0.85 [0.70-1.02]) and greater than (0.86 [0.74-1.01]) the median. Results were similar by histotype. CONCLUSIONS AND RELEVANCE: The findings of this study suggest that genetic susceptibility to ovarian cancer based on currently identified common genetic variants does not appear to modify the protective association between frequent aspirin use and ovarian cancer risk. Future work should continue to explore the role of aspirin use for ovarian cancer prevention among individuals who are at higher risk for ovarian cancer