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Body shape phenotypes combining multiple anthropometric traits have been linked to postmenopausal breast cancer (BC). However, underlying biological pathways remain poorly understood. This study investigated to what extent the associations of body shapes with postmenopausal BC risk is mediated by biochemical markers. The study included 176,686 postmenopausal women from UK Biobank. Four body shape phenotypes were derived from principal component (PC) analysis of height, weight, body mass index, waist and hip circumferences, and waist-to-hip ratio (WHR). The four-way decomposition of the total effect was used to estimate mediation and interaction effects simultaneously as well as the mediated proportions. After 10.9 years median follow-up, 6,396 incident postmenopausal BC were diagnosed. There was strong evidence of positive associations between PC1 (general obesity) and PC2 (tall, low WHR), and BC risk. The association of PC1 with BC risk was positively mediated by testosterone and negatively by insulin-like growth factor-1 (IGF-1), with the overall proportion mediated (sum of the mediated interaction and pure indirect effect (PIE)) accounting for 11.4% (95% confidence intervals: 5.1 to 17.8%) and -12.2% (-20.5% to -4.0%) of the total effect, respectively. Small proportions of the association between PC2 and BC were mediated by IGF-1 (PIE: 2.8% (0.6 to 4.9%)), and sex hormone-binding globulin (SHBG) (PIE: -6.1% (-10.9% to -1.3%)). Our findings are consistent with differential pathways linking different body shapes with BC risk, with a suggestive mediation through testosterone and IGF-1 in the relationship of a generally obese body shape and BC risk, while IGF-1 and SHBG may mediate a tall/lean body shape-BC risk association., (© 2024. The Author(s).)

Purpose: To provide an overview on how the application of metabolomics (high-throughput characterization of metabolites from cells, organs, tissues, or biofluids) to population-based studies may inform our understanding of breast cancer etiology., Methods: We evaluated studies that applied metabolomic analyses to prediagnostic blood samples from prospective epidemiologic studies to identify circulating metabolites associated with breast cancer risk, overall and by breast cancer subtype and menopausal status. We provide some important considerations for the application and interpretation of metabolomics approaches in this context., Results: Overall, specific lipids and amino acids were indicated as the most common metabolite classes associated with breast cancer development. However, comparison of results across studies is challenging because of heterogeneity in laboratory techniques, analytical methods, sample size, and applied statistical methods., Conclusion: Metabolomics is being increasingly applied to population-based studies for the identification of new etiologic hypotheses and/or mechanisms related to breast cancer development. Despite its success in applications to epidemiology, studies of larger sample size with detailed information on menopausal status, breast cancer subtypes, and repeated biologic samples collected over time are needed to improve comparison of results between studies and enhance validation of results, allowing potential clinical translation of findings.

The overall goal of the annual Transdisciplinary Research in Energetics and Cancer (TREC) Training Workshop is to provide transdisciplinary training for scientists in energetics and cancer and clinical care. The 2022 Workshop included 27 early-to-mid career investigators (trainees) pursuing diverse TREC research areas in basic, clinical, and population sciences. The 2022 trainees participated in a gallery walk, an interactive qualitative program evaluation method, to summarize key takeaways related to program objectives. Writing groups were formed and collaborated on this summary of the 5 key takeaways from the TREC Workshop. The 2022 TREC Workshop provided a targeted and unique networking opportunity that facilitated meaningful collaborative work addressing research and clinical needs in energetics and cancer. This report summarizes the 2022 TREC Workshop's key takeaways and future directions for innovative transdisciplinary energetics and cancer research., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations., Methods: We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty., Results: Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk., Conclusions: These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types., (© 2022. The Author(s).)

Three metabolite patterns have previously shown prospective inverse associations with the risk of aggressive prostate cancer within the European Prospective Investigation into Cancer and Nutrition (EPIC). Here, we investigated dietary and lifestyle correlates of these three prostate cancer-related metabolite patterns, which included: 64 phosphatidylcholines and three hydroxysphingomyelins (Pattern 1), acylcarnitines C18:1 and C18:2, glutamate, ornithine, and taurine (Pattern 2), and 8 lysophosphatidylcholines (Pattern 3). In a two-stage cross-sectional discovery (n = 2524) and validation (n = 518) design containing 3042 men free of cancer in EPIC, we estimated the associations of 24 dietary and lifestyle variables with each pattern and the contributing individual metabolites. Associations statistically significant after both correction for multiple testing (False Discovery Rate = 0.05) in the discovery set and at p < 0.05 in the validation set were considered robust. Intakes of alcohol, total fish products, and its subsets total fish and lean fish were positively associated with Pattern 1. Body mass index (BMI) was positively associated with Pattern 2, which appeared to be driven by a strong positive BMI-glutamate association. Finally, both BMI and fatty fish were inversely associated with Pattern 3. In conclusion, these results indicate associations of fish and its subtypes, alcohol, and BMI with metabolite patterns that are inversely associated with risk of aggressive prostate cancer.

Background: Breast cancer incidence is increasing rapidly in Latin America, with a higher proportion of cases among young women than in developed countries. Studies have linked inflammation to breast cancer development, but data is limited in premenopausal women, especially in Latin America., Methods: We investigated the associations between serum biomarkers of chronic inflammation (interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), leptin, adiponectin) and risk of premenopausal breast cancer among 453 cases and 453 matched, population-based controls from Chile, Colombia, Costa Rica, and Mexico. Odds ratios (OR) were estimated using conditional logistic regression models. Analyses were stratified by size and hormonal receptor status of the tumors., Results: IL-6 (OR per standard deviation (SD)  = 1.33 (1.11-1.60)) and TNF-α (OR per SD  = 1.32 (1.11-1.58)) were positively associated with breast cancer risk in fully adjusted models. Evidence of heterogeneity by estrogen receptor (ER) status was observed for IL-8 (P-homogeneity = 0.05), with a positive association in ER-negative tumors only. IL-8 (P-homogeneity = 0.06) and TNF-α (P-homogeneity = 0.003) were positively associated with risk in the largest tumors, while for leptin (P-homogeneity = 0.003) a positive association was observed for the smallest tumors only., Conclusions: The results of this study support the implication of chronic inflammation in breast cancer risk in young women in Latin America. Largest studies of prospective design are needed to confirm these findings in premenopausal women., (© 2022. The Author(s).)

Ultra-processed food intake has been linked to an increased risk of breast cancer in Western populations. No data are available in the Latin American population although the consumption of ultra-processed foods is increasing rapidly in this region. We evaluated the association of ultra-processed food intake to breast cancer risk in a case-control study including 525 cases (women aged 20-45 years) and 525 matched population-based controls from Chile, Colombia, Costa Rica and Mexico. The degree of processing of foods was classified according to the NOVA classification. Overall, the major contributors to ultra-processed food intake were ready-to-eat/heat foods (18.2%), cakes and desserts (16.7%), carbonated and industrial fruit juice beverages (16.7%), breakfast cereals (12.9%), sausages and reconstituted meat products (12.1%), industrial bread (6.1%), dairy products and derivatives (7.6%) and package savoury snacks (6.1%). Ultra-processed food intake was positively associated with the risk of breast cancer in adjusted models (OR T3-T1 =1.93; 95% CI=1.11 to 3.35). Specifically, a higher risk was observed with oestrogen receptor positive breast cancer (OR T3-T1 =2.44, (95% CI=1.01 to 5.90, P-trend=0.049), while no significant association was observed with oestrogen receptor negative breast cancer (OR T3-T1 =1.87, 95% CI=0.43 to 8.13, P-trend=0.36). Our findings suggest that the consumption of ultra-processed foods might increase the risk of breast cancer in young women in Latin America. Further studies should confirm these findings and disentangle specific mechanisms relating ultra-processed food intake and carcinogenic processes in the breast., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Metabolomics is a promising molecular tool for identifying novel etiological pathways leading to cancer. In an earlier prospective study among pre- and postmenopausal women not using exogenous hormones, we observed a higher risk of breast cancer associated with higher blood concentrations of one metabolite (acetylcarnitine) and a lower risk associated with higher blood concentrations of seven others (arginine, asparagine, phosphatidylcholines (PCs) aa C36:3, ae C34:2, ae C36:2, ae C36:3, and ae C38:2)., Methods: To identify determinants of these breast cancer-related metabolites, we conducted a cross-sectional analysis to identify their lifestyle and anthropometric correlates in 2358 women, who were previously included as controls in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition cohort and not using exogenous hormones at blood collection. Associations of each metabolite concentration with 42 variables were assessed using linear regression models in a discovery set of 1572 participants. Significant associations were evaluated in a validation set (n = 786)., Results: For the metabolites previously associated with a lower risk of breast cancer, concentrations of PCs ae C34:2, C36:2, C36:3, and C38:2 were negatively associated with adiposity and positively associated with total and saturated fat intakes. PC ae C36:2 was also negatively associated with alcohol consumption and positively associated with two scores reflecting adherence to a healthy lifestyle. Asparagine concentration was negatively associated with adiposity. Arginine and PC aa C36:3 concentrations were not associated to any of the factors examined. For the metabolite previously associated with a higher risk of breast cancer, acetylcarnitine, a positive association with age was observed., Conclusions: These associations may indicate possible mechanisms underlying associations between lifestyle and anthropometric factors, and risk of breast cancer. Further research is needed to identify potential non-lifestyle correlates of the metabolites investigated., (© 2021. The Author(s).)

Pooling metabolomics data across studies is often desirable to increase the statistical power of the analysis. However, this can raise methodological challenges as several preanalytical and analytical factors could introduce differences in measured concentrations and variability between datasets. Specifically, different studies may use variable sample types (e.g., serum versus plasma) collected, treated, and stored according to different protocols, and assayed in different laboratories using different instruments. To address these issues, a new pipeline was developed to normalize and pool metabolomics data through a set of sequential steps: (i) exclusions of the least informative observations and metabolites and removal of outliers; imputation of missing data; (ii) identification of the main sources of variability through principal component partial R-square (PC-PR2) analysis; (iii) application of linear mixed models to remove unwanted variability, including samples' originating study and batch, and preserve biological variations while accounting for potential differences in the residual variances across studies. This pipeline was applied to targeted metabolomics data acquired using Biocrates AbsoluteIDQ kits in eight case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Comprehensive examination of metabolomics measurements indicated that the pipeline improved the comparability of data across the studies. Our pipeline can be adapted to normalize other molecular data, including biomarkers as well as proteomics data, and could be used for pooling molecular datasets, for example in international consortia, to limit biases introduced by inter-study variability. This versatility of the pipeline makes our work of potential interest to molecular epidemiologists.

Background: While mammographic density is one of the strongest risk factors for breast cancer, little is known about its determinants, especially in young women. We applied targeted metabolomics to identify circulating metabolites specifically associated with mammographic density in premenopausal women. Then, we aimed to identify potential correlates of these biomarkers to guide future research on potential modifiable determinants of mammographic density., Methods: A total of 132 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, hexose) were measured by tandem liquid chromatography/mass spectrometry in plasma samples from 573 premenopausal participants in the Mexican Teachers' Cohort. Associations between metabolites and percent mammographic density were assessed using linear regression models, adjusting for breast cancer risk factors and accounting for multiple tests. Mean concentrations of metabolites associated with percent mammographic density were estimated across levels of several lifestyle and metabolic factors., Results: Sphingomyelin (SM) C16:1 and phosphatidylcholine (PC) ae C30:2 were inversely associated with percent mammographic density after correction for multiple tests. Linear trends with percent mammographic density were observed for SM C16:1 only in women with body mass index (BMI) below the median (27.4) and for PC ae C30:2 in women with a BMI over the median. SM C16:1 and PC ae C30:2 concentrations were positively associated with cholesterol (total and HDL) and inversely associated with number of metabolic syndrome components., Conclusions: We identified new biomarkers associated with mammographic density in young women. The association of these biomarkers with mammographic density and metabolic parameters may provide new perspectives to support future preventive actions for breast cancer., (© 2021. The Author(s).)

Background: There is convincing evidence demonstrating that body size characteristics such as adiposity and height are associated with breast cancer in westernized countries. However, little is known about this relationship in North African countries currently undergoing nutritional transition and industrialization. The aim of this study was to explore associations between various body size characteristics, silhouette trajectories and the risk of breast cancer among Moroccan women., Methods: In this case-control study conducted in the Fez region (2016-2017), detailed measures of body size were collected for 300 cases of breast cancer and 300 matched controls. Unconditional logistic regression was used to assess the association between body size and breast cancer risk adjusting for confounding factors., Results: Higher waist circumference and hip circumference were positively associated with breast cancer risk in pre- (highest [T3] vs. lowest tertile [T1]: OR = 2.92, 95% confidence intervals [CI]: 1.33-6.42; OR = 3.00, 95% CI: 1.42-6.33, respectively) and post-menopausal women (T3 vs. T1: OR = 4.46, 95% CI: 1.86-10.66; OR = 4.08, 95% CI: 1.76-9.42, respectively). Body shape at younger ages (6-11 years) was inversely associated with the risk of breast cancer in premenopausal women (large vs. lean silhouette: OR = 0.31, 95% CI: 0.12-0.80). Women with the greatest increase in body shape trajectory had higher risk for both pre- and post-menopausal breast cancer (T3 vs. T1: OR = 2.74, 95% CI: 1.03-7.26; OR = 3.56, 95% CI: 1.34-9.44, respectively)., Conclusion: Our findings suggest that adiposity, body shape at younger ages, and silhouette trajectory may play a role in the development of pre- and post-menopausal breast cancer among Moroccan women. Larger-scale prospective studies are needed to confirm our findings and to explore these associations with breast cancer subtypes.

Cumulating evidence in Caucasian women suggests a positive association between height and premenopausal breast cancer risk and a negative association with overall adiposity; however data from Latin America are scarce. We investigated the associations between excess adiposity, body shape evolution across life, and risk of premenopausal breast cancer among 406 cases (women aged 20-45) and 406 matched population-based controls from Chile, Colombia, Costa Rica, and Mexico. Negative associations between adult adiposity and breast cancer risk were observed in adjusted models (body mass index (BMI): Odds ratio (OR) per 1 kg/m 2  = 0.93; 95% confidence interval = 0.89-0.96; waist circumference (WC): OR per 10 cm = 0.81 (0.69-0.96); hip circumference (HC): OR per 10 cm = 0.80 (0.67-0.95)). Height and leg length were not associated with risk. In normal weight women (18.5 ≤ BMI < 25), women with central obesity (WC > 88 cm) had an increased risk compared to women with normal WC (OR = 3.60(1.47-8.79)). Residuals of WC over BMI showed positive associations when adjusted for BMI (OR per 10 cm = 1.38 (0.98-1.94)). Body shape at younger ages and body shape evolution were not associated with risk. No heterogeneity was observed by receptor status. In this population of Latin American premenopausal women, different fat distributions in adulthood were differentially associated with risk of breast cancer.

Background: Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study., Methods: Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS)., Results: Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03-1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03-1.06 and 1.04, 95% CI 1.02-1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94-0.98; 0.96, 95% CI 0.94-0.99; and 0.96, 95% CI 0.95-0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS., Conclusions: Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.

Background: Metabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk., Methods: A nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression., Results: Among women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70-0.90), asparagine (OR = 0.83 (0.74-0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76-0.90)), aa C36:3 (OR = 0.84 (0.77-0.93)), ae C34:2 (OR = 0.85 (0.78-0.94)), ae C36:2 (OR = 0.85 (0.78-0.88)), and ae C38:2 (OR = 0.84 (0.76-0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11-1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06-1.24)) and PC ae C36:3 (OR = 0.88 (0.82-0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity., Conclusions: These findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.

In the past decades, obesity and overweight prevalence has been rising worldwide, in both men and women. In France, the prevalence of overweight in adults was 49% in 2015 (54% among men and 44% among women), including 17% of obese adults. According to the last evaluation performed by IARC in 2017, overweight and obesity are established risk factors for 13 cancer sites with risk estimates per 5kg/m 2 varying largely depending on the cancer site. In 2015 in France, 5.4% of cancer cases could be attributed to excess weight, corresponding to 18,600 cases, including 3400 colon cancers, 2600 kidney cancers, 4500 breast cancers and 2500 endometrial cancers. Obesity is also related to worse prognosis for some cancers, in particular breast and colon cancers. Obesity in children and adolescents, also rising in many countries, has also been associated to an increase in adult cancer risk. A major cause of obesity is a disequilibrium in energy balance favoured by a diet rich in processed food, red meat, trans and saturated fatty acids, sweetened foods and beverages and poor in fruits and vegetables, legumes and whole grains. Main national and international recommendations to reduce the prevalence of obesity are to have a balanced diet and regular physical activity., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

In March 2011, the Myanmar Government transitioned to a nominally civilian parliamentary government, resulting in dramatic increases in international investments and tenuous peace in some regions. In March 2015, Community Partners International, the Women's Refugee Commission, and four community-based organisations (CBOs) assessed community-based sexual and reproductive health (SRH) services in eastern Myanmar amidst the changing political contexts in Myanmar and Thailand. The team conducted 12 focus group discussions among women of reproductive age (18-49 years) with children under five and interviewed 12 health workers in Kayin State, Myanmar. In Mae Sot and Chiang Mai, Thailand, the team interviewed 20 representatives of CBOs serving the border regions. Findings are presented through the socioecological lens to explore gender-based violence (GBV) specifically, to examine continued and emerging issues in the context of the political transition. Cited GBV includes ongoing sexual violence/rape by the military and in the community, trafficking, intimate partner violence, and early marriage. Despite the political transition, women continue to be at risk for military sexual violence, are caught in the burgeoning economic push-pull drivers, and experience ongoing restrictive gender norms, with limited access to SRH services. There is much fluidity, along with many connections and interactions among the contributing variables at all levels of the socioecological model; based on a multisectoral response, continued support for innovative, community-based SRH services that include medical and psychosocial care are imperative for ethnic minority women to gain more agency to freely exercise their SR rights.

Background: Receptor activator of nuclear factor kappa-B (RANK)-signaling is involved in tumor growth and spread in experimental models. Binding of RANK ligand (RANKL) to RANK activates signaling, which is inhibited by osteoprotegerin (OPG). We have previously shown that circulating soluble RANKL (sRANKL) and OPG are associated with breast cancer risk. Here we extend these findings to provide the first data on pre-diagnosis concentrations of sRANKL and OPG and risk of breast cancer-specific and overall mortality after a breast cancer diagnosis., Methods: Two thousand six pre- and postmenopausal women with incident invasive breast cancer (1620 (81%) with ER+ disease) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were followed-up for mortality. Pre-diagnosis concentrations of sRANKL and OPG were quantified in baseline serum samples using an enzyme-linked immunosorbent assay and electrochemiluminescent assay, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer-specific and overall mortality were calculated using Cox proportional hazards regression models., Results: Especially in women with ER+ disease, higher circulating OPG concentrations were associated with higher risk of breast cancer-specific (quintile 5 vs 1 HR 1.77 [CI 1.03, 3.04]; p trend 0.10) and overall mortality (q5 vs 1 HR 1.39 [CI 0.94, 2.05]; p trend 0.02). sRANKL and the sRANKL/OPG ratio were not associated with mortality following a breast cancer diagnosis., Conclusions: High pre-diagnosis endogenous concentrations of OPG, the decoy receptor for RANKL, were associated with increased risk of death after a breast cancer diagnosis, especially in those with ER+ disease. These results need to be confirmed in well-characterized patient cohorts.

Many studies have demonstrated that lifestyle factors, including diet, may influence cancer survival. The number of cancer survivors is increasing worldwide and little is known about long-term diet changes in people who had cancer. We studied 53,981 women from the prospective E3N-EPIC cohort study with available dietary data in 1993 and 2005, among whom 4,619 had a cancer diagnosis inbetween (including n = 2,699 breast cancers). We evaluated the potential impact of a cancer diagnosis (comparing women with cancer to women with no cancer) on changes in FV consumption using multivariable linear regression models considering cancer site, stage at diagnosis and socioeconomic factors. Compared to women with no cancer, a statistically significant increase in FV consumption (β=+2.65%, [1.22-4.09]) was observed in women who had cancer, and this association appeared to be driven by breast cancer exclusively. The increase in FV consumption was larger in women who had an advanced stage of breast cancer (stages II-IV) (β=+7.23%, [3.92-10.5]) than in women with stages 0-I (β=+2.03%, [-0.20 to 4.26]). Women with no partner and no children were those having the highest increase in FV consumption (β=+18.71%, [6.51-30.91]). These changes were only observed in specific SE groups. When considering adherence to guidelines, the proportion of women who consumed less than 7.5 portions a day in 1993 and more in 2005 was greater in women with advanced breast cancer. More research is now needed to understand how the inequities we observed impact the long-term health after cancer., (© 2018 UICC.)

Etiological differences among breast cancer (BC) subtypes have not been clearly established, especially among young women in Latin America. This study examined the relationship between reproductive factors and BC subtypes among 288 BC cases (20-45 years) and population-based matched controls in four Latin American countries. Immunohistochemistry was determined centrally. Associations between BC and reproductive factors were determined. Older age at first full-term pregnancy (FFTP) (Odds Ratio (OR) = 1.11; 95% Confidence Interval (CI), 1.04-1.19 per year), longer time between menarche and FFTP (OR = 1.12; 95%CI: 1.04-1.20 per year), and older age at last pregnancy (OR = 1.10; 95%CI, 1.02-1.19 per year) were associated with an increased risk of estrogen receptor positive (ER+) tumors (n = 122). Ever pregnant (OR = 0.35; 95%CI, 0.13-0.96), number of childbirths (OR = 0.64; 95%CI, 0.47-0.87 per child), time since last birth (OR = 0.92; 95%CI, 0.85-0.99 per year), and history of breastfeeding (OR = 0.23; 95%CI, 0.09-0.58) were inversely associated with the risk of ER+ tumor. Older age at menarche (OR = 0.63; 95%CI, 0.45-0.89 per year) and longer duration of breastfeeding (OR = 0.97; 95%CI, 0.94-1.01 per month) were inversely associated with estrogen receptor negative (ER-) tumors (n = 48). Reproductive factors may be differentially associated with BC subtypes in young Latin American women.

Although adult obesity has been associated with poor breast cancer survival, data on adiposity at different periods in life and its lifelong evolution are scarce. Our aims were to assess the associations between breast cancer survival and body size during childhood, puberty and early adulthood and body size trajectories from childhood to adulthood. Self-assessed body size at age 8, at puberty, at age 20-25 and at age 35-40 and trajectories of body size of 4,662 breast cancer survivors from the prospective E3N cohort were studied in relation to risk of death from any cause, death from breast cancer and second invasive cancer event using multivariate Cox regression models. Four trajectories of body size were identified (T1 "moderate increase," T2 "stable/low increase," T3 "increase at puberty" and T4 "constantly high"). Compared with stable body size, an increase in body size during adult life was associated with an increased risk of death from any cause (HR T1 vs. T2 = 1.27; 95% CI = 1.01-1.60) and an increased risk of second invasive cancer event (HR T1 vs. T2 = 1.25; 95% CI = 1.06-1.47). Silhouettes at various ages were not associated with survival. Our results suggest that the evolution of body size from childhood to adulthood has a long-term influence on breast cancer survival. Although these results need to be confirmed, this work sheds light on the need to combine lifelong approaches to current BMI to better identify breast cancer survivors who are at higher risk of recurrence or second primary cancer, or of death., (© 2017 UICC.)

Background: In addition to tumor characteristics and lifestyle factors, cancer relapses are often related to the risk of death but have not been jointly studied. We investigate the prognostic factors of recurrent events and death after a diagnosis of breast cancer and predict individual deaths including a history of recurrences., Methods: The E3N (Etude Epidémiologique auprès de Femmes de la Mutuelle Générale de l'Education Nationale) study is a prospective cohort study that was initiated in 1990 to investigate factors associated with the most common types of cancer. Overall survival and three types of recurrent events were considered: locoregional recurrence, metastasis, and second primary breast cancer. Recurrent events and death were analyzed using a joint frailty model., Results: The analysis included 4926 women from the E3N cohort diagnosed with a first primary invasive breast cancer between June 1990 and June 2008; during the follow-up, 1334 cases had a recurrence (median time of follow-up is 7.2 years) and 469 women died. Cases with high grade, large tumor size, axillary nodal involvement, and negative estrogen and progesterone receptors had a higher risk of recurrence or death. Furthermore, smoking increased the risk of relapse. For cases with a medium risk profile in terms of tumor characteristics and lifestyle factors, the probability of dying between 5 and 10 years after diagnosis was 6, 20 and 36% for 0, 1 or 2 recurrences within the first 5 years after diagnosis, respectively., Conclusions: Our study showed the importance of considering baseline lifestyle characteristics and history of relapses to dynamically predict the risk of death in breast cancer cases. Medical experience coupled with an estimate of a patient's survival probability that considers all available information for this patient would enable physicians to make better informed decisions regarding their actions and thus improve clinical output.

Background: Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting., Materials and Methods: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours., Results: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor., Conclusion: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. [br]All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Receptor activator of nuclear factor-kappa B (RANK)-RANK ligand (RANKL) signaling promotes mammary tumor development in experimental models. Circulating concentrations of soluble RANKL (sRANKL) may influence breast cancer risk via activation of RANK signaling; this may be modulated by osteoprotegerin (OPG), the decoy receptor for RANKL. sRANKL and breast cancer risk by hormone receptor subtype has not previously been investigated. A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. This study included 1,976 incident invasive breast cancer cases [estrogen receptor positive (ER+), n = 1,598], matched 1:1 to controls. Women were pre- or postmenopausal at blood collection. Serum sRANKL was quantified using an ELISA, serum OPG using an electrochemiluminescent assay. Risk ratios (RR) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. Associations between sRANKL and breast cancer risk differed by tumor hormone receptor status ( P het = 0.05). Higher concentrations of sRANKL were positively associated with risk of ER+ breast cancer [5th vs. 1st quintile RR 1.28 (95% CI, 1.01-1.63); P trend = 0.20], but not ER- disease. For both ER+ and estrogen and progesterone receptor positive (ER+PR+) breast cancer, results considering the sRANKL/OPG ratio were similar to those for sRANKL; we observed a suggestive inverse association between the ratio and ER-PR- disease [5th vs. 1st quintile RR = 0.60 (0.31-1.14); P trend = 0.03]. This study provides the first large-scale prospective data on circulating sRANKL and breast cancer. We observed limited evidence for an association between sRANKL and breast cancer risk. Cancer Prev Res; 10(9); 525-34. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Flavonoids have been shown to inhibit colon cancer cell proliferation in vitro and protect against colorectal carcinogenesis in animal models. However, epidemiological evidence on the potential role of flavonoid intake in colorectal cancer (CRC) development remains sparse and inconsistent. We evaluated the association between dietary intakes of total flavonoids and their subclasses and risk of development of CRC, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cohort of 477,312 adult men and women were recruited in 10 European countries. At baseline, dietary intakes of total flavonoids and individual subclasses were estimated using centre-specific validated dietary questionnaires and composition data from the Phenol-Explorer database. During an average of 11 years of follow-up, 4,517 new cases of primary CRC were identified, of which 2,869 were colon (proximal = 1,298 and distal = 1,266) and 1,648 rectal tumours. No association was found between total flavonoid intake and the risk of overall CRC (HR for comparison of extreme quintiles 1.05, 95% CI 0.93-1.18; p-trend = 0.58) or any CRC subtype. No association was also observed with any intake of individual flavonoid subclasses. Similar results were observed for flavonoid intake expressed as glycosides or aglycone equivalents. Intake of total flavonoids and flavonoid subclasses, as estimated from dietary questionnaires, did not show any association with risk of CRC development., (© 2016 UIC.)

Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (OR Q4-Q1  = 1.26; 95% CI 1.00-1.58; P trend  = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (OR Q4-Q1  = 1.29; 95% CI 1.02-1.62; P trend  = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation., (© 2016 UICC.)

Background: The Mediterranean diet (MD) has been proposed as a means for cancer prevention, but little evidence has been accrued regarding its potential to prevent pancreatic cancer. We investigated the association between the adherence to the MD and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort., Methods: Over half a million participants from 10 European countries were followed up for over 11 years, after which 865 newly diagnosed exocrine pancreatic cancer cases were identified. Adherence to the MD was estimated through an adapted score without the alcohol component (arMED) to discount alcohol-related harmful effects. Cox proportional hazards regression models, stratified by age, sex and centre, and adjusted for energy intake, body mass index, smoking status, alcohol intake and diabetes status at recruitment, were used to estimate hazard ratios (HRs) associated with pancreatic cancer and their corresponding 95% confidence intervals (CIs)., Results: Adherence to the arMED score was not associated with risk of pancreatic cancer (HR high vs low adherence=0.99; 95% CI: 0.77-1.26, and HR per increments of two units in adherence to arMED=1.00; 95% CI: 0.94-1.06). There was no convincing evidence for heterogeneity by smoking status, body mass index, diabetes or European region. There was also no evidence of significant associations in analyses involving microscopically confirmed cases, plausible reporters of energy intake or other definitions of the MD pattern., Conclusions: A high adherence to the MD is not associated with pancreatic cancer risk in the EPIC study.

Adult height and sitting height may reflect genetic and environmental factors, including early life nutrition, physical and social environments. Previous studies have reported divergent associations for height and chronic disease mortality, with positive associations observed for cancer mortality but inverse associations for circulatory disease mortality. Sitting height might be more strongly associated with insulin resistance; however, data on sitting height and mortality is sparse. Using the European Prospective Investigation into Cancer and Nutrition study, a prospective cohort of 409,748 individuals, we examined adult height and sitting height in relation to all-cause and cause-specific mortality. Height was measured in the majority of participants; sitting height was measured in ~253,000 participants. During an average of 12.5 years of follow-up, 29,810 deaths (11,931 from cancer and 7,346 from circulatory disease) were identified. Hazard ratios (HR) with 95% confidence intervals (CI) for death were calculated using multivariable Cox regression within quintiles of height. Height was positively associated with cancer mortality (men: HRQ5 vs. Q1 = 1.11, 95%CI = 1.00-1.24; women: HRQ5 vs. Q1 = 1.17, 95%CI = 1.07-1.28). In contrast, height was inversely associated with circulatory disease mortality (men: HRQ5 vs. Q1 = 0.63, 95%CI = 0.56-0.71; women: HRQ5 vs. Q1 = 0.81, 95%CI = 0.70-0.93). Although sitting height was not associated with cancer mortality, it was inversely associated with circulatory disease (men: HRQ5 vs. Q1 = 0.64, 95%CI = 0.55-0.75; women: HRQ5 vs. Q1 = 0.60, 95%CI = 0.49-0.74) and respiratory disease mortality (men: HRQ5 vs. Q1 = 0.45, 95%CI = 0.28-0.71; women: HRQ5 vs. Q1 = 0.60, 95%CI = 0.40-0.89). We observed opposing effects of height on cancer and circulatory disease mortality. Sitting height was inversely associated with circulatory disease and respiratory disease mortality.

Background: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating levels of copper, zinc and their ratio (Cu/Zn) in relation to hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBD) and gall bladder and biliary tract (GBTC) cancers., Methods: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. Serum zinc and copper levels were measured in baseline blood samples by total reflection X-ray fluorescence in cancer cases (HCC n=106, IHDB n=34, GBTC n=96) and their matched controls (1:1). The Cu/Zn ratio, an indicator of the balance between the micronutrients, was computed. Multivariable adjusted odds ratios and 95% confidence intervals (OR; 95% CI) were used to estimate cancer risk., Results: For HCC, the highest vs lowest tertile showed a strong inverse association for zinc (OR=0.36; 95% CI: 0.13-0.98, P trend =0.0123), but no association for copper (OR=1.06; 95% CI: 0.45-2.46, P trend =0.8878) in multivariable models. The calculated Cu/Zn ratio showed a positive association for HCC (OR=4.63; 95% CI: 1.41-15.27, P trend =0.0135). For IHBC and GBTC, no significant associations were observed., Conclusions: Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings.

Background: Circulating osteoprotegerin (OPG), a member of the receptor activator of nuclear factor kappa-B (RANK) axis, may influence breast cancer risk via its role as the decoy receptor for both the RANK ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Circulating OPG and breast cancer risk has been examined in only one prior study., Methods: A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 2008 incident invasive breast cancer cases (estrogen receptor (ER)+, n = 1622; ER-, n = 386), matched 1:1 to controls, were included in the analysis. Women were predominantly postmenopausal at blood collection (77%); postmenopausal women included users and non-users of postmenopausal hormone therapy (HT). Serum OPG was quantified with an electrochemiluminescence assay. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression., Results: The associations between OPG and ER+ and ER- breast cancer differed significantly. Higher concentrations of OPG were associated with increased risk of ER- breast cancer (top vs. bottom tertile RR = 1.93 [95% CI 1.24-3.02]; p trend  = 0.03). We observed a suggestive inverse association for ER+ disease overall and among women premenopausal at blood collection. Results for ER- disease did not differ by menopausal status at blood collection (p het  = 0.97), and we observed no heterogeneity by HT use at blood collection (p het  ≥ 0.43) or age at breast cancer diagnosis (p het  ≥ 0.30)., Conclusions: This study provides the first prospective data on OPG and breast cancer risk by hormone receptor subtype. High circulating OPG may represent a novel risk factor for ER- breast cancer.

Purpose: Several mechanistic studies support a role of cholesterol or its metabolites in breast cancer etiology, but associations have been inconsistent in epidemiological studies. In observational studies, possible reverse causation must be accounted for using a prospective design. We investigated prospective associations between pre-diagnostic serum lipid concentrations [total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides], and both breast cancer risk and survival in the E3N cohort study., Methods: Analyses were performed on 583 cases from the E3N prospective cohort diagnosed between 1994 and 2005, and 1,043 controls matched on date, age, recruitment center and menopausal status at blood collection. Odds ratios (OR) and 95% confidence intervals were estimated using conditional logistic regression. Risks of recurrence were estimated among cases using Cox proportional hazards model. Models were adjusted for lifestyle risk factors and mutually adjusted for lipid concentrations. Survival analyses were additionally adjusted for tumor characteristics., Results: Overall, there was no association between any serum lipid and breast cancer risk or survival. In stratified analyses, statistically significant interaction was observed between TC and menopausal status (P interaction  = 0.05) and between TC and waist circumference (P interaction  = 0.03), although the ORs did not reach statistical significance in any of the strata. There was no statistically significant effect modification by BMI, time between blood donation and diagnosis or ER status., Conclusions: Our results suggest that serum lipids are not associated with breast cancer risk overall, but that menopausal status and waist circumference should be considered in further studies.

Obesity has been associated with poor breast cancer prognosis, however most studies have focused on body mass index (BMI) and few have considered the distribution of adipose tissue. We investigated associations between prediagnostic adiposity and breast cancer survival, considering BMI, waist and hip circumferences (WC and HC), and waist-to-hip ratio (WHR). Analyses included 3,006 women from the French E3N prospective cohort study diagnosed with primary invasive breast cancer between 1995 and 2008. We investigated overall, breast cancer-specific, and disease-free survival, overall and according to stage, menopausal and hormonal status and year of diagnosis, using Cox proportional hazard models adjusted for tumor characteristics and lifestyle risk factors. Women with a prediagnostic HC > 100 cm were at increased risk of death from all causes (hazard ratio (HR)>100 vs < 95 cm  = 1.38, 95% Confidence Interval (CI) = 1.02-1.86, Ptrend  = 0.02) and from breast cancer (HR>100 vs < 95 cm  = 1.50, CI = 1.03-2.17, Ptrend  = 0.03), and of second invasive cancer event (HR>100 vs < 95 cm  = 1.36, CI = 1.11-1.67, Ptrend  = 0.002), compared to those with HC <95 cm. Associations were stronger after adjustment for BMI. BMI, WC and WHR were not associated with survival after breast cancer. Our study underlines the importance of going beyond BMI when studying the association between adiposity and breast cancer survival. Further studies should be conducted to confirm our results on hip circumference., (© 2016 UICC.)

Background: Studies of the role of dietary factors in epithelial ovarian cancer (EOC) development have been limited, and no specific dietary factors have been consistently associated with EOC risk., Objective: We used a nutrient-wide association study approach to systematically test the association between dietary factors and invasive EOC risk while accounting for multiple hypothesis testing by using the false discovery rate and evaluated the findings in an independent cohort., Design: We assessed dietary intake amounts of 28 foods/food groups and 29 nutrients estimated by using dietary questionnaires in the EPIC (European Prospective Investigation into Cancer and Nutrition) study (n = 1095 cases). We selected 4 foods/nutrients that were statistically significantly associated with EOC risk when comparing the extreme quartiles of intake in the EPIC study (false discovery rate = 0.43) and evaluated these factors in the NLCS (Netherlands Cohort Study; n = 383 cases). Cox regression models were used to estimate HRs and 95% CIs., Results: None of the 4 dietary factors that were associated with EOC risk in the EPIC study (cholesterol, polyunsaturated and saturated fat, and bananas) were statistically significantly associated with EOC risk in the NLCS; however, in meta-analysis of the EPIC study and the NLCS, we observed a higher risk of EOC with a high than with a low intake of saturated fat (quartile 4 compared with quartile 1; overall HR: 1.21; 95% CI: 1.04, 1.41)., Conclusion: In the meta-analysis of both studies, there was a higher risk of EOC with a high than with a low intake of saturated fat., (© 2016 American Society for Nutrition.)

The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-hr diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC = 122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/day, HR = 0.80, 95% CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g/day, HR = 0.71, 95% CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g/day, HR = 0.92, 95% CI: 0.68-1.25). There was no association between saturated fats (HR = 1.08, 95% CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR = 0.86, 95% CI: 0.73-1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk., (© 2015 UICC.)

The aim was to investigate the association between pre-diagnostic intakes of polyphenol classes (flavonoids, lignans, phenolic acids, stilbenes, and other polyphenols) in relation to breast cancer survival (all-cause and breast cancer-specific mortality). We used data from the European Prospective Investigation into Cancer and Nutrition cohort. Pre-diagnostic usual diet was assessed using dietary questionnaires, and polyphenol intakes were estimated using the Phenol-Explorer database. We followed 11,782 breast cancer cases from time of diagnosis until death, end of follow-up or last day of contact. During a median of 6 years, 1482 women died (753 of breast cancer). We related polyphenol intake to all-cause and breast cancer-specific mortality using Cox proportional hazard models with time since diagnosis as underlying time and strata for age and country. Among postmenopausal women, an intake of lignans in the highest versus lowest quartile was related to a 28 % lower risk of dying from breast (adjusted model: HR, quartile 4 vs. quartile 1, 0.72, 95 % CI 0.53; 0.98). In contrast, in premenopausal women, a positive association between lignan intake and all-cause mortality was found (adjusted model: HR, quartile 4 vs. quartile 1, 1.63, 95 % CI 1.03; 2.57). We found no association for other polyphenol classes. Intake of lignans before breast cancer diagnosis may be related to improved survival among postmenopausal women, but may on the contrary worsen the survival for premenopausal women. This suggests that the role of phytoestrogens in breast cancer survival is complex and may be dependent of menopausal status.

The objective of the present study was to conduct the first systematic review and meta-analysis of prospective studies investigating the associations between total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels and the risk of breast cancer. Relevant studies were identified in PubMed (up to January 2014). Inclusion criteria were original peer-reviewed publications with a prospective design. Random-effects models were used to estimate summary hazard ratios (HR) and 95% CI. Distinction was made between studies that did or did not exclude cancer cases diagnosed during the first years of follow-up, thereby eliminating potential preclinical bias. Overall, the summary HR for the association between TC and breast cancer risk was 0.97 (95% CI 0.94, 1.00; dose-response per 1 mmol/l increment, thirteen studies), and that between HDL-C and breast cancer risk was 0.86 (95% CI 0.69, 1.09; dose-response per 1 mmol/l increment, six studies), with high heterogeneity (I2= 67 and 47%, respectively). For studies that eliminated preclinical bias, an inverse association was observed between the risk of breast cancer and TC (dose-response HR 0.94 (95% CI 0.89, 0.99), seven studies, I2= 78%; highest v. lowest HR 0.82 (95% CI 0.66, 1.02), nine studies, I2= 81%) and HDL-C (dose-response HR 0.81 (95% CI 0.65, 1.02), five studies, I2= 30 %; highest v. lowest HR 0.82 (95% CI 0.69, 0.98), five studies, I2= 0%). There was no association observed between LDL-C and the risk of breast cancer (four studies). The present meta-analysis confirms the evidence of a modest but statistically significant inverse association between TC and more specifically HDL-C and the risk of breast cancer, supported by mechanistic plausibility from experimental studies. Further large prospective studies that adequately control for preclinical bias are needed to confirm the results on the role of cholesterol level and its fractions in the aetiology of breast cancer.

Although experimental data suggest a potentially protective involvement of dietary fiber in prostate carcinogenesis, very few prospective studies have investigated the relation between dietary fiber intake and prostate cancer risk, and those have had inconsistent results. Our objective was to study the association between dietary fiber intake (overall, insoluble, soluble, and from different sources, such as cereals, vegetables, fruits, and legumes) and prostate cancer risk. Stratifications by excess weight status, insulin-like growth factors, and amount of alcohol intake were also considered. This prospective analysis included 3313 men from the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort who completed at least 3 24-h dietary records. One hundred thirty-nine incident prostate cancers were diagnosed between 1994 and 2007 (median follow-up of 12.6 y). Associations between quartiles of energy-adjusted dietary fiber intake and prostate cancer risk were characterized by multivariate Cox proportional hazards models. Prostate cancer risk was inversely associated with total dietary fiber intake (HR of quartile 4 vs. quartile 1 = 0.47; 95% CI: 0.27, 0.81; P = 0.001), insoluble (HR = 0.46; 95% CI: 0.27, 0.78; P = 0.001), and legume (HR = 0.55; 95% CI: 0.32, 0.95; P = 0.04) fiber intakes. In contrast, we found no association between prostate cancer risk and soluble (P = 0.1), cereal (P = 0.7), vegetable (P = 0.9), and fruit (P = 0.4) fiber intakes. In conclusion, dietary fiber intake (total, insoluble, and from legumes but not soluble or from cereals, vegetables, and fruits) was inversely associated with prostate cancer risk, consistent with mechanistic data.

Experimental studies provided evidence about mechanisms by which cholesterol, especially high density lipoprotein cholesterol (HDL-C), could influence carcinogenesis, notably through antioxidant and anti-inflammatory properties. However, prospective studies that investigated the associations between specific lipid metabolism biomarkers and cancer risk provided inconsistent results. The objective was to investigate the prospective associations between total cholesterol (T-C), HDL-C, low density lipoprotein cholesterol, apolipoproteins A1 (apoA1) and B, and triglycerides and overall, breast and prostate cancer risk. Analyses were performed on 7,557 subjects of the Supplémentation en Vitamines et Minéraux Antioxydants Study, a nationwide French cohort study. Biomarkers of lipid metabolism were measured at baseline and analyzed regarding the risk of first primary incident cancer (N = 514 cases diagnosed during follow-up, 1994-2007), using Cox proportional hazards models. T-C was inversely associated with overall (HR(1mmol/L increment) = 0.91, 95 % CI 0.82-1.00; P = 0.04) and breast (HR(1mmol/L increment) = 0.83, 95 % CI 0.69-0.99; P = 0.04) cancer risk. HDL-C was also inversely associated with overall (HR(1mmol/L increment) = 0.61, 95 % CI 0.46-0.82; P = 0.0008) and breast (HR(1mmol/L increment) = 0.48, 95 % CI 0.28-0.83; P = 0.009) cancer risk. Consistently, apoA1 was inversely associated with overall (HR(1g/L increment) = 0.56, 95 % CI 0.39-0.82; P = 0.003) and breast (HR(1g/L increment) = 0.36, 95 % CI 0.18-0.73; P = 0.004) cancer risk. This prospective study suggests that pre-diagnostic serum levels of T-C, HDL-C and ApoA1 are associated with decreased overall and breast cancer risk. The confirmation of a role of cholesterol components in cancer development, by further large prospective and experimental studies, may have important implications in terms of public health, since cholesterol is already crucial in cardiovascular prevention.

Background: Mechanistic hypotheses suggest a potential effect of dietary fiber on breast carcinogenesis through the modulation of insulin-like growth factor bioactivity, estrogen metabolism and inflammation. An association between dietary fiber intake and breast cancer risk has been suggested in epidemiological studies but remains inconclusive. In particular, data is lacking regarding the different types of dietary fibers., Objective: The objective was to investigate the prospective relationship between dietary fiber intake and breast cancer risk, taking into account different types of dietary fiber (overall, insoluble, soluble and from different food sources: cereals, vegetables, fruits and legumes)., Design: 4684 women from the SU.VI.MAX cohort were included in this analysis as they completed at least three 24h-dietary records within the first two years of follow-up. Among them, 167 incident invasive breast cancers were diagnosed during a median follow-up of 12.6 years (between 1994 and 2007). The associations between quartiles of dietary fiber intake and breast cancer risk were characterized using multivariate Cox proportional hazards models., Results: Total fiber intake was not associated with breast cancer risk (HR(Quartile4vs.Quartile1) = 1.29 (95%CI 0.66-2.50), P-trend = 0.5), nor was fiber intake from cereals (P-trend = 0.1), fruits (P-trend = 0.9) and legumes (P-trend = 0.3). In contrast, vegetable fiber intake was related to a decreased risk of breast cancer (HR(Q4vs.Q1) = 0.50 (0.29-0.88), P-trend = 0.03). Overall vegetable intake (in g/day) was not associated with breast cancer risk (P-trend = 0.2)., Conclusion: This prospective study suggests that vegetable fiber intake may contribute to reduce breast cancer risk, in line with experimental mechanistic data.