Dairy foods and nutrients in relation to risk of ovarian cancer and major histological subtypes

Inconsistent results for the role of dairy food intake in relation to ovarian cancer risk may reflect the potential adverse effects of lactose, which has been hypothesized to increase gonadotropin levels, and the beneficial anti-proliferative effects of calcium and vitamin D. Using data from the New England case-control study (1909 cases; 1989 controls) we examined dairy foods and nutrients in relation to risk of ovarian cancer overall, histological subtypes, and rapidly fatal versus less aggressive disease. We used logistic regression and polytomous logistic regression to estimate odds ratios and 95% confidence intervals. In models that were simultaneously adjusted for total (dietary plus supplements) calcium, total vitamin D and lactose, we observed a decreased overall risk of ovarian cancer with high intake of total calcium (Quartile 4 (Q4, >1319 mg/day) vs. Quartile 1 (Q1, 559 IU/day vs. Q1, <164 IU/day, OR=0.51, 95% CI=0.34–0.76) and endometrioid tumors (Q4 vs. Q1, OR=0.55, 95% CI=0.39-0.80). We found no evidence that lactose intake influenced ovarian cancer risk, or that risk varied by tumor aggressiveness in the analyses of intake of dairy foods and nutrients. The overall inverse association with high intake of calcium, and the inverse associations of calcium and vitamin D with specific histological subtypes warrant further investigation

Gene Expression Signature of Normal Cell-of-Origin Predicts Ovarian Tumor Outcomes

The potential role of the cell-of-origin in determining the tumor phenotype has been raised, but not adequately examined. We hypothesized that distinct cells-of-origin may play a role in determining ovarian tumor phenotype and outcome. Here we describe a new cell culture medium for in vitro culture of paired normal human ovarian (OV) and fallopian tube (FT) epithelial cells from donors without cancer. While these cells have been cultured individually for short periods of time, to our knowledge this is the first long-term culture of both cell types from the same donors. Through analysis of the gene expression profiles of the cultured OV/FT cells we identified a normal cell-of-origin gene signature that classified primary ovarian cancers into OV-like and FT-like subgroups; this classification correlated with significant differences in clinical outcomes. The identification of a prognostically significant gene expression signature derived solely from normal untransformed cells is consistent with the hypothesis that the normal cell-of-origin may be a source of ovarian tumor heterogeneity and the associated differences in tumor outcome

Combined population genomic screening for three high-risk conditions in Australia: a modelling study

BACKGROUND: No previous health-economic evaluation has assessed the impact and cost-effectiveness of offering combined adult population genomic screening for mutliple high-risk conditions in a national public healthcare system. METHODS: This modeling study assessed the impact of offering combined genomic screening for hereditary breast and ovarian cancer, Lynch syndrome and familial hypercholesterolaemia to all young adults in Australia, compared with the current practice of clinical criteria-based testing for each condition separately. The intervention of genomic screening, assumed as an up-front single cost in the first annual model cycle, would detect pathogenic variants in seven high-risk genes. The simulated population was 18–40 year-olds (8,324,242 individuals), modelling per-sample test costs ranging AU$100–$1200 (base-case AU$200) from the year 2023 onwards with testing uptake of 50 FINDINGS: Over the population lifetime (to age 80 years), the model estimated that genomic screening per-100,000 individuals would lead to 747 QALYs gained by preventing 63 cancers, 31 CHD cases and 97 deaths. In the total model population, this would translate to 31,094 QALYs gained by preventing 2612 cancers, 542 non-fatal CHD events and 4047 total deaths. At AU$200 per-test, genomic screening would require an investment of AU$832 million for screening of 50$23,926 (∼£12,050/€14,110/US$15,345) per QALY gained over the status quo. In scenario analysis with 3$4758/QALY was obtained. Sensitivity analysis for the base case indicated that combined genomic screening would be cost-effective under 70% of simulations, cost-saving under 25% and not cost-effective under 5%. Threshold analysis showed that genomic screening would be cost-effective under the AU$50,000/QALY willingness-to-pay threshold at per-test costs up to AU$325 (∼£164/€192/US$208). INTERPRETATION: Our findings suggest that offering combined genomic screening for high-risk conditions to young adults would be cost-effective in the Australian public healthcare system, at currently realistic testing costs. Other matters, including psychosocial impacts, ethical and societal issues, and implementation challenges, also need consideration. FUNDING: Australian Government, Department of Health, Medical Research Future Fund, Genomics Health Futures Mission (APP2009024). National Heart Foundation Future Leader Fellowship (102604)

Reproductive factors and risk of mortality in the European Prospective Investigation into Cancer and Nutrition; a cohort study

Abstract Background Reproductive events are associated with important physiologic changes, yet little is known about how reproductive factors influence long-term health in women. Our objective was to assess the relation of reproductive characteristics with all-cause and cause-specific mortality risk. Methods The analysis was performed within the European Investigation into Cancer and Nutrition prospective cohort study, which enrolled >500,000 women and men from 1992 to 2000, who were residing in a given town/geographic area in 10 European countries. The current analysis included 322,972 eligible women aged 25–70 years with 99 % complete follow-up for vital status. We assessed reproductive characteristics reported at the study baseline including parity, age at the first birth, breastfeeding, infertility, oral contraceptive use, age at menarche and menopause, total ovulatory years, and history of oophorectomy/hysterectomy. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for mortality were determined using Cox proportional hazards regression models adjusted for menopausal status, body mass index, physical activity, education level, and smoking status/intensity and duration. Results During a mean follow-up of 12.9 years, 14,383 deaths occurred. The HR (95 % CI) for risk of all-cause mortality was lower in parous versus nulliparous women (0.80; 0.76–0.84), in women who had ever versus never breastfed (0.92; 0.87–0.97), in ever versus never users of oral contraceptives (among non-smokers; 0.90; 0.86–0.95), and in women reporting a later age at menarche (≥15 years versus <12; 0.90; 0.85–0.96; P for trend = 0.038). Conclusions Childbirth, breastfeeding, oral contraceptive use, and a later age at menarche were associated with better health outcomes. These findings may contribute to the development of improved strategies to promote better long-term health in women

Meat and haem iron intake in relation to glioma in the European Prospective Investigation into Cancer and Nutrition study

Diets high in red or processed meat have been associated positively with some cancers, and several possible underlying mechanisms have been proposed, including iron-related pathways. However, the role of meat intake in adult glioma risk has yielded conflicting findings because of small sample sizes and heterogeneous tumour classifications. The aim of this study was to examine red meat, processed meat and iron intake in relation to glioma risk in the European Prospective Investigation into Cancer and Nutrition study. In this prospective cohort study, 408751 individuals from nine European countries completed demographic and dietary questionnaires at recruitment. Multivariable Cox proportional hazards models were used to examine intake of red meat, processed meat, total dietary iron and haem iron in relation to incident glioma. During an average follow-up of 14.1 years, 688 incident glioma cases were diagnosed. There was no evidence that any of the meat variables (red, processed meat or subtypes of meat) or iron (total or haem) were associated with glioma; results were unchanged when the first 2 years of follow-up were excluded. This study suggests that there is no association between meat or iron intake and adult glioma. This is the largest prospective analysis of meat and iron in relation to glioma and as such provides a substantial contribution to a limited and inconsistent literature

Circulating inflammatory biomarkers, adipokines and breast cancer risk—a case-control study nested within the EPIC cohort

Background Inflammation has been hypothesized to play a role in the development and progression of breast cancer and might differently impact breast cancer risk among pre and postmenopausal women. We performed a nested case-control study to examine whether pre-diagnostic circulating concentrations of adiponectin, leptin, c-reactive protein (CRP), tumour necrosis factor-alpha, interferon-gamma and 6 interleukins were associated with breast cancer risk, overall and by menopausal status. Methods Pre-diagnostic levels of inflammatory biomarkers were measured in plasma from 1558 case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We used conditional logistic regression to estimate the odds ratios (ORs) of breast cancer at blood collection, per one standard deviation increase in biomarker concentration. Results Cases were diagnosed at a mean age of 61.4 years on average 8.6 years after blood collection. No statistically significant association was observed between inflammatory markers and breast cancer risk overall. In premenopausal women, borderline significant inverse associations were observed for leptin, leptin-to-adiponectin ratio and CRP [OR= 0.89 (0.77-1.03), OR= 0.88 (0.76-1.01) and OR= 0.87 (0.75-1.01), respectively] while positive associations were observed among postmenopausal women [OR= 1.16 (1.05-1.29), OR= 1.11 (1.01-1.23), OR= 1.10 (0.99-1.22), respectively]. Adjustment for BMI strengthened the estimates in premenopausal women [leptin: OR = 0.83 (0.68-1.00), leptin-to-adiponectin ratio: OR = 0.80 (0.66-0.97), CRP: OR = 0.85 (0.72-1.00)] but attenuated the estimates in postmenopausal women [leptin: OR = 1.09 (0.96-1.24), leptin-to-adiponectin ratio: OR = 1.02 (0.89-1.16), CRP: OR = 1.04 (0.92-1.16)]. Conclusions Associations between CRP, leptin and leptin-to-adiponectin ratio with breast cancer risk may represent the dual effect of obesity by menopausal status although this deserves further investigation

Reproductive factors and risk of mortality in the European Prospective Investigation into Cancer and Nutrition; a cohort study.

BACKGROUND: Reproductive events are associated with important physiologic changes, yet little is known about how reproductive factors influence long-term health in women. Our objective was to assess the relation of reproductive characteristics with all-cause and cause-specific mortality risk. METHODS: The analysis was performed within the European Investigation into Cancer and Nutrition prospective cohort study, which enrolled >500,000 women and men from 1992 to 2000, who were residing in a given town/geographic area in 10 European countries. The current analysis included 322,972 eligible women aged 25-70 years with 99 % complete follow-up for vital status. We assessed reproductive characteristics reported at the study baseline including parity, age at the first birth, breastfeeding, infertility, oral contraceptive use, age at menarche and menopause, total ovulatory years, and history of oophorectomy/hysterectomy. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for mortality were determined using Cox proportional hazards regression models adjusted for menopausal status, body mass index, physical activity, education level, and smoking status/intensity and duration. RESULTS: During a mean follow-up of 12.9 years, 14,383 deaths occurred. The HR (95 % CI) for risk of all-cause mortality was lower in parous versus nulliparous women (0.80; 0.76-0.84), in women who had ever versus never breastfed (0.92; 0.87-0.97), in ever versus never users of oral contraceptives (among non-smokers; 0.90; 0.86-0.95), and in women reporting a later age at menarche (≥15 years versus <12; 0.90; 0.85-0.96; P for trend = 0.038). CONCLUSIONS: Childbirth, breastfeeding, oral contraceptive use, and a later age at menarche were associated with better health outcomes. These findings may contribute to the development of improved strategies to promote better long-term health in women

Circulating prolactin and in situ breast cancer risk in the European EPIC cohort: a case-control study

Introduction: The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention. Methods: We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects. Results: We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2 = 1.35 (95% CI 1.04-1.76), P-trend = 0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (P-het = 0.98) or baseline HT use (P-het = 0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (P-trend = 0.06 vs P-trend = 0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors = 4 years after blood donation (P-trend = 0.01 vs P-trend = 0.63; P-het = 0.04) and among nulliparous women compared to parous women (P-trend = 0.03 vs P-trend = 0.15; P-het = 0.07). Conclusions: Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer. The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention

Insulin/IGF and Sex Hormone Axes in Human Endometrium and Associations with Endometrial Cancer Risk Factors

Given an ordered set of points and an ordered set of geometric objects in the plane, we are interested in finding a non-crossing matching between point-object pairs. In this paper, we address the algorithmic problem of determining whether a non-crossing matching exists between a given point-object pair. We show that when the objects we match the points to are finite point sets, the problem is NP-complete in general, and polynomial when the objects are on a line or when their size is at most 2. When the objects are line segments, we show that the problem is NP-complete in general, and polynomial when the segments form a convex polygon or are all on a line. Finally, for objects that are straight lines, we show that the problem of finding a min-max non-crossing matching is NP-complete. © 2012 Elsevier B.V.SCOPUS: ar.jinfo:eu-repo/semantics/publishe