Publications by authors named "Sabina Rinaldi"

257 Publications

Determinants of Obesity and Metabolic Health in the Afghan Population: Protocol, Methodology, and Preliminary Results.

J Epidemiol Glob Health 2022 Jan 7. Epub 2022 Jan 7.

Nutrition and Metabolism Section, International Agency for Research On Cancer (IARC/WHO), 150 Cours Albert Thomas, 69372, Cedex 08, Lyon, France.

Background: Non-communicable diseases (NCDs) cause more than 70% of deaths worldwide and share modifiable risk factors including obesity and metabolic abnormalities. Over the past 15 years, many changes in lifestyle, dietary patterns, physical activity, and socioeconomic status have been observed in the Afghan population. This study aims to investigate which specific lifestyle factors, dietary patterns, and characteristics of Westernization are associated with an increased risk of being overweight or obese and with poor metabolic health in the Afghan population.

Methods: A population-based cross-sectional study was conducted where a total of 729 male and female participants were recruited. Face-to-face interviews and anthropometric measurements were conducted by trained health staff using standardized questionnaires which included information on socio-demographic and housing characteristics, income, occupation, ethnicity, personal and family medical history, stress, anthropometry, diet, and physical activity. Bioelectric impedance analysis (BIA) was used to estimate body composition, including overall body fatness. Physical activity was measured using the short version of the International Physical Activity Questionnaire (IPAQ). For a comprehensive assessment of dietary intake, a food-frequency questionnaire (FFQ) specific to the Afghan population was developed which included all local food items relevant to the population. Lipid profile and fasting glucose were measured in a local laboratory. Biospecimens were collected using dried blood spots (DBS) and dried stool cards to perform microbiome and biomarker-based research.

Discussion: This is the first study which will assess dietary patterns, lifestyle factors, and their association with obesity and metabolic health in Afghanistan. Such a study will aid the development of dietary and lifestyle guidelines in Afghanistan which will promote better health and educate people to make healthy food choices. The findings will also help in designing and implementing effective public health strategies to promote a healthy lifestyle and prevent the epidemic of overweight and obesity, and, hence, reduce the burden of non-communicable diseases in the region.
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http://dx.doi.org/10.1007/s44197-021-00026-0DOI Listing
January 2022

Lifestyle correlates of eight breast cancer-related metabolites: a cross-sectional study within the EPIC cohort.

BMC Med 2021 Dec 10;19(1):312. Epub 2021 Dec 10.

CIBER Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.

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.
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http://dx.doi.org/10.1186/s12916-021-02183-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662901PMC
December 2021

Adherence to the South African food based dietary guidelines may reduce breast cancer risk in black South African women: the South African Breast Cancer (SABC) study.

Public Health Nutr 2021 Nov 29:1-17. Epub 2021 Nov 29.

Nutrition and Metabolism Branch, International Agency for Research on Cancer - WHO, Albert Thomas, Lyon, France.

Objective: To determine the level of adherence and to assess the association between higher adherence to the South African food based dietary guidelines (SAFBDG) and breast cancer risk.

Design: Population-based, case-control study (the South African Breast Cancer study) matched on age and demographic settings. Validated questionnaires were used to collect dietary and epidemiological data. To assess adherence to the SAFBDG, a nine-point adherence score (out of eleven guidelines) was developed, using suggested adherence cut-points for scoring each recommendation (0 and 1). When the association between higher adherence to the SAFBDG and breast cancer risk was assessed, data-driven tertiles among controls were used as cut-points for scoring each recommendation (0, 0·5 and 1). OR and 95 % CI were estimated using multivariate logistic regression models.

Setting: Soweto, South Africa.

Participants: Black urban women, 396 breast cancer cases and 396 controls.

Results: After adjusting for potential confounders, higher adherence (>5·0) to the SAFBDG v. lower adherence (<3·5) was statistically significantly inversely associated with breast cancer risk overall (OR = 0·56, 95 % CI 0·38, 0·85), among postmenopausal women (OR = 0·64, 95 % CI 0·40, 0·97) as well as for oestrogen-positive breast cancers (OR = 0·51, 95 % CI 0·32, 0·89). Only 32·3 % of cases and 39·1 % of controls adhered to at least half (a score >4·5) of the SAFBDG.

Conclusions: Higher adherence to the SAFBDG may reduce breast cancer risk in this population. The concerning low levels of adherence to the SAFBDG emphasise the need for education campaigns and to create healthy food environments in South Africa to increase adherence to the SAFBDG.
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http://dx.doi.org/10.1017/S1368980021004675DOI Listing
November 2021

Dietary Patterns and Breast Cancer Risk in Black Urban South African Women: The SABC Study.

Nutrients 2021 Nov 16;13(11). Epub 2021 Nov 16.

International Agency for Research on Cancer, Nutrition and Metabolism Branch, IARC-WHO, 150 Cours Albert Thomas, 69372 Lyon, France.

A total of 396 breast cancer cases and 396 population-based controls from the South African Breast Cancer study (SABC) matched on age and demographic settings was included. Validated questionnaires were used to collect dietary and epidemiological data. Dietary patterns were derived using principal component analysis with a covariance matrix from 33 food groups. Odds ratios and 95% confidence intervals were estimated using conditional logistic regression. A traditional, a cereal-dairy breakfast and a processed food dietary pattern were identified, which together explained 40.3% of the total variance in the diet. After adjusting for potential confounders, the traditional dietary pattern and cereal-dairy breakfast dietary pattern were inversely associated with breast cancer risk (highest tertile versus lowest tertile) (OR = 0.72, 95%CI: 0.57-0.89, -trend = 0.004 and OR = 0.73, 95%CI: 0.59-0.90, -trend = 0.004, respectively). The processed food dietary pattern was not significantly associated with breast cancer risk. The results of this study show that a traditional dietary pattern and a cereal-dairy breakfast dietary pattern may reduce the risk of developing breast cancer in this population.
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http://dx.doi.org/10.3390/nu13114106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617719PMC
November 2021

Endogenous Circulating Sex Hormone Concentrations and Colon Cancer Risk in Postmenopausal Women: A Prospective Study and Meta-Analysis.

JNCI Cancer Spectr 2021 Dec 28;5(6):pkab084. Epub 2021 Sep 28.

Faculty of Health Sciences, Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.

Background: Observational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk, but epidemiologic studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results.

Methods: We investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone-binding globulin (SHBG) with colon cancer risk in a nested case-control study of 1028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were noncurrent users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios and 95% confidence intervals to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided.

Results: In the multivariable model, a nonstatistically significantly positive relationship was found between circulating estrone and colon cancer risk (odds ratio per log 1-unit increment=1.17 [95% confidence interval=1.00 to 1.38]; odds ratio =1.33 [95% confidence interval=0.89 to 1.97], =.20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the dose-response meta-analysis, no clear evidence of associations were found between circulating estradiol and estrone concentrations with colorectal, colon, and rectal cancer risk.

Conclusion: Our observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex hormones and colon or rectal cancer in postmenopausal women.
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http://dx.doi.org/10.1093/jncics/pkab084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8598284PMC
December 2021

Incidence and mortality trends of thyroid cancer from 1980 to 2016.

Swiss Med Wkly 2021 Oct 5;151:w30029. Epub 2021 Nov 5.

Division of Chronic Disease Epidemiology, Epidemiology, Biostatistics, and Prevention Institute, University of Zurich, Switzerland.

Aims Of The Study: Thyroid cancer incidence rates have been increasing globally over past decades. However, no study examining those trends in the canton of Zurich, Switzerland exists. In this study, we describe the incidence and mortality trends of thyroid cancer in the canton of Zurich during a 37-year period (1980-2016) including factors such as sex, histological subtypes and age at diagnosis.

Methods: We analysed population-based cancer registry data from 1980-2016 for the canton of Zurich, Switzerland. We estimated the age-standardised incidence and mortality rates using the European standard population. Joinpoint regression was used to detect average annual percentage changes (AAPCs) and their corresponding 95% confidence intervals (CIs).

Results: We included 2972 primary cases of thyroid cancer (72.3% in women). The papillary cases accounted for the majority of incident cases (65.8%). In 2016, women had a higher age-standardised incidence rate than men for both papillary (10.4 and 3.3, respectively, per 100,000) and non-papillary (1.6 and 0.7, respectively, per 100,000) thyroid cancer. In both men and women, the incidence rates of thyroid cancer increased significantly over the study period with AAPCs of 1.4% (95% CI 0.6-2.2%) and 2.6% (95% CI 2-3.1%), respectively. These increasing incidence trends are mainly driven by papillary thyroid cancer with AAPCs of 3.4% in men (95% CI 2.3% to 4.4%) and 4.3% in women (95% CI 3.7% to 5%). Mortality rates significantly decreased in both sexes (men AAPC -3.6%, 95% CI -4.7% to -2.4%; women AAPC -3.7%, 95% CI -4.8% to -2.6%).

Conclusions: Our results show significantly increasing age-standardised incidence rates of thyroid cancer over time in both sexes, mainly due to papillary thyroid cancer, the most frequent histological subtype, and the only subtype for which a significant increase was observed. It is possible that many indolent thyroid cancers, and more specifically papillary microcarcinomas, are increasingly diagnosed, which may not lead to symptoms if undetected. Therefore, targeted diagnostic strategies are necessary to avoid overdiagnosis of thyroid cancer. Nevertheless, we cannot completely exclude a partly true increase.
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http://dx.doi.org/10.4414/smw.2021.w30029DOI Listing
October 2021

A New Pipeline for the Normalization and Pooling of Metabolomics Data.

Metabolites 2021 Sep 17;11(9). Epub 2021 Sep 17.

Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain.

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.
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http://dx.doi.org/10.3390/metabo11090631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467830PMC
September 2021

The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium.

PLoS Med 2021 09 20;18(9):e1003786. Epub 2021 Sep 20.

Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.

Background: Excess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecular mechanisms underlying these relationships are poorly understood. In this study, we sought to identify circulating metabolites that predispose kidney cancer and to evaluate the extent to which they are influenced by body mass index (BMI).

Methods And Findings: We assessed the association between circulating levels of 1,416 metabolites and incident kidney cancer using pre-diagnostic blood samples from up to 1,305 kidney cancer case-control pairs from 5 prospective cohort studies. Cases were diagnosed on average 8 years after blood collection. We found 25 metabolites robustly associated with kidney cancer risk. In particular, 14 glycerophospholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 × 10-8). In contrast, 4 amino acids, including glutamate (OR for 1 SD = 1.39, 95% CI: 1.20 to 1.60, p = 1.6 × 10-5), were positively associated with risk. Adjusting for BMI partly attenuated the risk association for some-but not all-metabolites, whereas other known risk factors of kidney cancer, such as smoking and alcohol consumption, had minimal impact on the observed associations. A mendelian randomisation (MR) analysis of the influence of BMI on the blood metabolome highlighted that some metabolites associated with kidney cancer risk are influenced by BMI. Specifically, elevated BMI appeared to decrease levels of several GPLs that were also found inversely associated with kidney cancer risk (e.g., -0.17 SD change [ßBMI] in 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2) levels per SD change in BMI, p = 3.4 × 10-5). BMI was also associated with increased levels of glutamate (ßBMI: 0.12, p = 1.5 × 10-3). While our results were robust across the participating studies, they were limited to study participants of European descent, and it will, therefore, be important to evaluate if our findings can be generalised to populations with different genetic backgrounds.

Conclusions: This study suggests a potentially important role of the blood metabolome in kidney cancer aetiology by highlighting a wide range of metabolites associated with the risk of developing kidney cancer and the extent to which changes in levels of these metabolites are driven by BMI-the principal modifiable risk factor of kidney cancer.
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http://dx.doi.org/10.1371/journal.pmed.1003786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496779PMC
September 2021

Inflammation-Related Marker Profiling of Dietary Patterns and All-cause Mortality in the Melbourne Collaborative Cohort Study.

J Nutr 2021 Oct;151(10):2908-2916

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.

Background: Nutritional epidemiology research using self-reported dietary intake is prone to measurement error. Objective methods are being explored to overcome this limitation.

Objectives: We aimed to examine 1) the association between plasma markers related to inflammation and derive marker scores for dietary patterns [Mediterranean dietary score (MDS), energy-adjusted Dietary Inflammatory Index (E-DIITM), Alternative Healthy Eating Index 2010 (AHEI)] and 2) the associations of these marker scores with mortality.

Methods: Weighted marker scores were derived from the cross-sectional association between 30 plasma markers and each dietary score (assessed using food-frequency questionnaires) using linear regression for 770 participants in the Melbourne Collaborative Cohort Study (aged 50-82 y). Prospective associations between marker scores and mortality (n = 249 deaths) were assessed using Cox regression (median follow-up: 14.4 y).

Results: The MDS, E-DII, and AHEI were associated (P < 0.05) with 9, 14, and 11 plasma markers, respectively. Healthier diets (higher MDS and AHEI, and lower anti-inflammatory, E-DII) were associated with lower concentrations of kynurenines, neopterin, IFN-γ, cytokines, and C-reactive protein. Five of 6 markers common to the 3 dietary scores were components of the kynurenine pathway. The 3 dietary-based marker scores were highly correlated (Spearman ρ: -0.74, -0.82, and 0.93). Inverse associations (for 1-SD increment) were observed with all-cause mortality for the MDS marker score (HR: 0.84; 95% CI: 0.72-0.98) and the AHEI marker score (HR: 0.76; 95% CI: 0.66-0.89), whereas a positive association was observed with the E-DII marker score (HR: 1.18; 95% CI: 1.01-1.39). The same magnitude of effect was not observed for the respective dietary patterns.

Conclusions: Markers involved in inflammation-related processes are associated with dietary quality, including a substantial overlap between markers associated with the MDS, the E-DII, and the AHEI, especially kynurenines. Unfavorable marker scores, reflecting poorer-quality diets, were associated with increased mortality.
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http://dx.doi.org/10.1093/jn/nxab231DOI Listing
October 2021

Biomarkers of mammographic density in premenopausal women.

Breast Cancer Res 2021 07 23;23(1):75. Epub 2021 Jul 23.

International Agency for Research on Cancer (IARC/WHO), Nutrition and Metabolism Branch, CEDEX 08, 69372, Lyon, France.

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.
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http://dx.doi.org/10.1186/s13058-021-01454-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305592PMC
July 2021

Longitudinal associations of physical activity with plasma metabolites among colorectal cancer survivors up to 2 years after treatment.

Sci Rep 2021 07 2;11(1):13738. Epub 2021 Jul 2.

Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.

We investigated longitudinal associations of moderate-to-vigorous physical activity (MVPA) and light-intensity physical activity (LPA) with plasma concentrations of 138 metabolites after colorectal cancer (CRC) treatment. Self-reported physical activity data and blood samples were obtained at 6 weeks, and 6, 12 and 24 months post-treatment in stage I-III CRC survivors (n = 252). Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQp180 kit). Linear mixed models were used to evaluate confounder-adjusted longitudinal associations. Inter-individual (between-participant differences) and intra-individual associations (within-participant changes over time) were assessed as percentage difference in metabolite concentration per 5 h/week of MVPA or LPA. At 6 weeks post-treatment, participants reported a median of 6.5 h/week of MVPA (interquartile range:2.3,13.5) and 7.5 h/week of LPA (2.0,15.8). Inter-individual associations were observed with more MVPA being related (FDR-adjusted q-value < 0.05) to higher concentrations of arginine, citrulline and histidine, eight lysophosphatidylcholines, nine diacylphosphatidylcholines, 13 acyl-alkylphosphatidylcholines, two sphingomyelins, and acylcarnitine C10:1. No intra-individual associations were found. LPA was not associated with any metabolite. More MVPA was associated with higher concentrations of several lipids and three amino acids, which have been linked to anti-inflammatory processes and improved metabolic health. Mechanistic studies are needed to investigate whether these metabolites may affect prognosis.
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http://dx.doi.org/10.1038/s41598-021-92279-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253824PMC
July 2021

Association of markers of inflammation, the kynurenine pathway and B vitamins with age and mortality, and a signature of inflammaging.

J Gerontol A Biol Sci Med Sci 2021 Jun 12. Epub 2021 Jun 12.

Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia.

Background: Inflammation is a key feature of aging. We aimed to i) investigate the association of 34 blood markers potentially involved in inflammatory processes with age and mortality, ii) develop a signature of 'inflammaging'.

Methods: Thirty-four blood markers relating to inflammation, B vitamin status and the kynurenine pathway were measured in 976 participants in the Melbourne Collaborative Cohort Study at baseline (median age=59 years) and follow-up (median age=70 years). Associations with age and mortality were assessed using linear and Cox regression, respectively. A parsimonious signature of inflammaging was developed and its association with mortality was compared with two marker scores calculated across all markers associated with age and mortality, respectively.

Results: The majority of markers (30/34) were associated with age, with stronger associations observed for neopterin, cystatin C, IL-6, TNF-α, several markers of the kynurenine pathway and derived indices KTR (kynurenine/tryptophan ratio), PAr index (ratio of 4-pyridoxic acid and the sum of pyridoxal 5´-phosphate and pyridoxal), and HK:XA (3-hydroxykynurenine/xanthurenic acid ratio). Many markers (17/34) showed an association with mortality, in particular IL-6, neopterin, CRP, quinolinic acid, PAr index, and KTR. The inflammaging signature included ten markers and was strongly associated of mortality (HR per SD=1.40, 95%CI:1.24-1.57, P=2x10 -8), similar to scores based on all age-associated (HR=1.38, 95%CI:1.23-1.55, P=4x10 -8) and mortality-associated markers (HR=1.43, 95%CI:1.28-1.60, P=1x10 -10), respectively. Strong evidence of replication of the inflammaging signature association with mortality was found in the Hordaland Health Study.

Conclusion: Our study highlights the key role of the kynurenine pathway and vitamin B6 catabolism in aging, along with other well-established inflammation-related markers. A signature of inflammaging based on ten markers was strongly associated with mortality.
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http://dx.doi.org/10.1093/gerona/glab163DOI Listing
June 2021

Prospective analysis of circulating metabolites and endometrial cancer risk.

Gynecol Oncol 2021 08 5;162(2):475-481. Epub 2021 Jun 5.

Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands.

Background: Endometrial cancer is strongly associated with obesity and dysregulation of metabolic factors such as estrogen and insulin signaling are causal risk factors for this malignancy. To identify additional novel metabolic pathways associated with endometrial cancer we performed metabolomic analyses on pre-diagnostic plasma samples from 853 case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC).

Methods: A total of 129 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexoses, and sphingolipids) were measured by liquid chromatography-mass spectrometry. Conditional logistic regression estimated the associations of metabolites with endometrial cancer risk. An analysis focusing on clusters of metabolites using the bootstrap lasso method was also employed.

Results: After adjustment for body mass index, sphingomyelin [SM] C18:0 was positively (OR: 1.18, 95% CI: 1.05-1.33), and glycine, serine, and free carnitine (C0) were inversely (OR: 0.89, 95% CI: 0.80-0.99; OR: 0.89, 95% CI: 0.79-1.00 and OR: 0.91, 95% CI: 0.81-1.00, respectively) associated with endometrial cancer risk. Serine, C0 and two sphingomyelins were selected by the lasso method in >90% of the bootstrap samples. The ratio of esterified to free carnitine (OR: 1.14, 95% CI: 1.02-1.28) and that of short chain to free acylcarnitines (OR: 1.12, 95% CI: 1.00-1.25) were positively associated with endometrial cancer risk. Further adjustment for C-peptide or other endometrial cancer risk factors only minimally altered the results.

Conclusion: These findings suggest that variation in levels of glycine, serine, SM C18:0 and free carnitine may represent specific pathways linked to endometrial cancer development. If causal, these pathways may offer novel targets for endometrial cancer prevention.
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http://dx.doi.org/10.1016/j.ygyno.2021.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336647PMC
August 2021

Adherence to cancer prevention recommendations is associated with a lower breast cancer risk in black urban South African women.

Br J Nutr 2021 May 14:1-12. Epub 2021 May 14.

International Agency for Research on Cancer, Section of Nutrition and Metabolism, 150 cours Albert Thomas, 69372 Lyon, France.

Breast cancer prevention is of great importance to reduce high incidence in South Africa. This study aimed to investigate adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations and the association with breast cancer risk in black urban women from Soweto, South Africa. A total of 396 breast cancer cases and 396 population-based controls from the South African Breast Cancer study (SABC) matched on age and demographic settings were included. Validated questionnaires were used to collect dietary and epidemiological data. To assess adherence to these recommendations, an eight-point adherence score was developed, using tertiles among controls for scoring each recommendation (0, 0·5 and 1) with zero indicating the lowest adherence to the recommendations. OR and 95 % CI were estimated using multivariate logistic regression models to analyse associations between the WCRF/AICR score and breast cancer risk. Greater adherence (>4·5 v. <3·25) to the 2018 WCRF/AICR Cancer Prevention Recommendations was associated with a significant inverse association with breast cancer risk overall (OR = 0·54, 95 % CI 0·35, 0·91) and specifically in postmenopausal women (OR = 0·55, 95 % CI 0·34, 0·95), in cases with oestrogen positive and progesterone positive breast cancer subtypes (OR = 0·54, 95 % CI 0·39, 0·89 and OR = 0·68, 95 % CI 0·43, 0·89, respectively) and in obese women (OR = 0·52, 95 % CI 0·35, 0·81). No significant association with breast cancer risk was observed in premenopausal women. Greater adherence to the 2018 WCRF/AICR Cancer Prevention Recommendations may reduce breast cancer risk in this black urban population of Soweto. Adherence thereof should be encouraged and form a part of cost-effective breast cancer prevention guidelines.
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http://dx.doi.org/10.1017/S0007114521001598DOI Listing
May 2021

Metabolic signatures of greater body size and their associations with risk of colorectal and endometrial cancers in the European Prospective Investigation into Cancer and Nutrition.

BMC Med 2021 04 30;19(1):101. Epub 2021 Apr 30.

International Agency for Research on Cancer, World Health Organization, Lyon, France.

Background: The mechanisms underlying the obesity-cancer relationship are incompletely understood. This study aimed to characterise metabolic signatures of greater body size and to investigate their association with two obesity-related malignancies, endometrial and colorectal cancers, and with weight loss within the context of an intervention study.

Methods: Targeted mass spectrometry metabolomics data from 4326 participants enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and 17 individuals from a single-arm pilot weight loss intervention (Intercept) were used in this analysis. Metabolic signatures of body size were first determined in discovery (N = 3029) and replication (N = 1297) sets among EPIC participants by testing the associations between 129 metabolites and body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) using linear regression models followed by partial least squares analyses. Conditional logistic regression models assessed the associations between the metabolic signatures with endometrial (N = 635 cases and 648 controls) and colorectal (N = 423 cases and 423 controls) cancer risk using nested case-control studies in EPIC. Pearson correlation between changes in the metabolic signatures and weight loss was tested among Intercept participants.

Results: After adjustment for multiple comparisons, greater BMI, WC, and WHR were associated with higher levels of valine, isoleucine, glutamate, PC aa C38:3, and PC aa C38:4 and with lower levels of asparagine, glutamine, glycine, serine, lysoPC C17:0, lysoPC C18:1, lysoPC C18:2, PC aa C42:0, PC ae C34:3, PC ae C40:5, and PC ae C42:5. The metabolic signature of BMI (OR 1.50, 95% CI 1.30-1.74), WC (OR 1.46, 95% CI 1.27-1.69), and WHR (OR 1.54, 95% CI 1.33-1.79) were each associated with endometrial cancer risk. Risk of colorectal cancer was positively associated with the metabolic signature of WHR (OR: 1.26, 95% CI 1.07-1.49). In the Intercept study, a positive correlation was observed between weight loss and changes in the metabolic signatures of BMI (r = 0.5, 95% CI 0.06-0.94, p = 0.03), WC (r = 0.5, 95% CI 0.05-0.94, p = 0.03), and WHR (r = 0.6, 95% CI 0.32-0.87, p = 0.01).

Conclusions: Obesity is associated with a distinct metabolic signature comprising changes in levels of specific amino acids and lipids which is positively associated with both colorectal and endometrial cancer and is potentially reversible following weight loss.
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http://dx.doi.org/10.1186/s12916-021-01970-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086283PMC
April 2021

NMR Metabolite Profiles in Male Meat-Eaters, Fish-Eaters, Vegetarians and Vegans, and Comparison with MS Metabolite Profiles.

Metabolites 2021 Feb 20;11(2). Epub 2021 Feb 20.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.

Metabolomics may help to elucidate mechanisms underlying diet-disease relationships and identify novel risk factors for disease. To inform the design and interpretation of such research, evidence on diet-metabolite associations and cross-assay comparisons is needed. We aimed to compare nuclear magnetic resonance (NMR) metabolite profiles between meat-eaters, fish-eaters, vegetarians and vegans, and to compare NMR measurements to those from mass spectrometry (MS), clinical chemistry and capillary gas-liquid chromatography (GC). We quantified 207 serum NMR metabolite measures in 286 male participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford cohort. Using univariate and multivariate analyses, we found that metabolite profiles varied by diet group, especially for vegans; the main differences compared to meat-eaters were lower levels of docosahexaenoic acid, total n-3 and saturated fatty acids, cholesterol and triglycerides in very-low-density lipoproteins, various lipid factions in high-density lipoprotein, sphingomyelins, tyrosine and creatinine, and higher levels of linoleic acid, total n-6, polyunsaturated fatty acids and alanine. Levels in fish-eaters and vegetarians differed by metabolite measure. Concentrations of 13 metabolites measured using both NMR and MS, clinical chemistry or GC were mostly similar. In summary, vegans' metabolite profiles were markedly different to those of men consuming animal products. The studied metabolomics platforms are complementary, with limited overlap between metabolite classes.
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http://dx.doi.org/10.3390/metabo11020121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923783PMC
February 2021

Reproductive factors and risk of breast cancer in black South African women.

Cancer Causes Control 2021 Apr 20;32(4):415-422. Epub 2021 Jan 20.

Section of Nutrition and Metabolism, International Agency for Research On Cancer, 150, Cours Albert Thomas, 69008, Lyon, France.

Purpose: Breast cancer (BC) is increasing in black South African women, but few studies have investigated its risk factors.

Methods: We conducted an analysis of reproductive factors and BC risk in the South African Breast Cancer (SABC) study-a population-based case-control study of black South African women from Soweto that included 399 cases and 399 matched controls. Information on lifestyle and reproductive history was obtained by interviews. Conditional logistic regression was used to determine the association of reproductive factors with BC, adjusting for potential confounding factors.

Results: Seventy-five percent of all BC cases were ER+, 66% PR+, 30% HER2+, and 16% TN. None of the reproductive variables were associated with BC overall or by subtype in the overall population, nor in pre- (n = 135 cases) or in post-menopausal women separately. In HIV-negative pre-menopausal women (n = 97 cases), later age at first pregnancy and longer time between menarche and first full-time pregnancy were inversely related to BC risk (OR 0.89 (95% CI 0.82-0.97; and 0.93 95% CI 0.86-1.01, respectively).

Conclusion: In this population of black South African women, reproductive factors were not associated with BC risk.
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http://dx.doi.org/10.1007/s10552-021-01390-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075164PMC
April 2021

Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk: A Case-Control Study Nested within a European Prospective Cohort.

Cancer Epidemiol Biomarkers Prev 2021 01 20;30(1):182-192. Epub 2020 Oct 20.

Public Health Directorate, Oviedo, Spain.

Background: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation.

Methods: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively.

Results: Higher sRAGE concentrations were inversely associated with colorectal cancer (OR, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (OR, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (OR, 1.00; 95% CI, 0.68-1.48; for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99).

Conclusions: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within gene, pertaining to RAGE shedding, was associated with colorectal cancer risk.

Impact: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0855DOI Listing
January 2021

Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Am J Clin Nutr 2020 Oct 6. Epub 2020 Oct 6.

Institute of Risk Assessment Sciences, Utrecht University, Utrecht, Netherlands.

Background: Polyphenols are natural compounds with anticarcinogenic properties in cellular and animal models, but epidemiological evidence determining the associations of these compounds with thyroid cancer (TC) is lacking.

Objectives: The aim of this study was to evaluate the relations between blood concentrations of 36 polyphenols and TC risk in EPIC (the European Prospective Investigation into Cancer and Nutrition).

Methods: A nested case-control study was conducted on 273 female cases (210 papillary, 45 follicular, and 18 not otherwise specified TC tumors) and 512 strictly matched controls. Blood polyphenol concentrations were analyzed by HPLC coupled to tandem MS after enzymatic hydrolysis.

Results: Using multivariable-adjusted conditional logistic regression models, caffeic acid (ORlog2: 0.55; 95% CI: 0.33, 0.93) and its dehydrogenated metabolite, 3,4-dihydroxyphenylpropionic acid (ORlog2: 0.84; 95% CI: 0.71, 0.99), were inversely associated with differentiated TC risk. Similar results were observed for papillary TC, but not for follicular TC. Ferulic acid was also inversely associated only with papillary TC (ORlog2: 0.68; 95% CI: 0.51, 0.91). However, none of these relations was significant after Bonferroni correction for multiple testing. No association was observed for any of the remaining polyphenols with total differentiated, papillary, or follicular TC.

Conclusions: Blood polyphenol concentrations were mostly not associated with differentiated TC risk in women, although our study raises the possibility that high blood concentrations of caffeic, 3,4-dihydroxyphenylpropionic, and ferulic acids may be related to a lower papillary TC risk.
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http://dx.doi.org/10.1093/ajcn/nqaa277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779226PMC
October 2020

Adiposity and Endometrial Cancer Risk in Postmenopausal Women: A Sequential Causal Mediation Analysis.

Cancer Epidemiol Biomarkers Prev 2021 01 2;30(1):104-113. Epub 2020 Oct 2.

Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Background: Adiposity increases endometrial cancer risk, possibly through inflammation, hyperinsulinemia, and increasing estrogens. We aimed to quantify the mediating effects of adiponectin (anti-inflammatory adipocytokine); IL6, IL1-receptor antagonist, TNF receptor 1 and 2, and C-reactive protein (inflammatory status biomarkers); C-peptide (hyperinsulinemia biomarker); and free estradiol and estrone (estrogen biomarkers) in the adiposity-endometrial cancer link in postmenopausal women.

Methods: We used data from a case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Eligible women did not have cancer, hysterectomy, and diabetes; did not use oral contraceptives or hormone therapy; and were postmenopausal at recruitment. Mediating pathways from adiposity to endometrial cancer were investigated by estimating natural indirect (NIE) and direct (NDE) effects using sequential mediation analysis.

Results: The study included 163 cases and 306 controls. The adjusted OR for endometrial cancer for body mass index (BMI) ≥30 versus ≥18.5-<25 kg/m was 2.51 (95% confidence interval, 1.26-5.02). The ORs were 1.95 (1.01-3.74) through all biomarkers [72% proportion mediated (PM)] decomposed as: 1.35 (1.06-1.73) through pathways originating with adiponectin (33% PM); 1.13 (0.71-1.80) through inflammation beyond (the potential influence of) adiponectin (13% PM); 1.05 (0.88-1.24) through C-peptide beyond adiponectin and inflammation (5% PM); and 1.22 (0.89-1.67) through estrogens beyond preceding biomarkers (21% PM). The OR not through biomarkers was 1.29 (0.54-3.09). Waist circumference gave similar results.

Conclusions: Reduced adiponectin and increased inflammatory biomarkers, C-peptide, and estrogens mediated approximately 70% of increased odds of endometrial cancer in women with obesity versus normal weight.

Impact: If replicated, these results could have implications for identifying targets for intervention to reduce endometrial cancer risk in women with obesity.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0965DOI Listing
January 2021

Body size, silhouette trajectory and the risk of breast cancer in a Moroccan case-control study.

Breast Cancer 2020 Jul 6;27(4):748-758. Epub 2020 Mar 6.

Department of Epidemiology, Faculty of Medicine and Pharmacy, Fez, Morocco.

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.
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http://dx.doi.org/10.1007/s12282-020-01072-5DOI Listing
July 2020

Anthropometry, body shape in early-life and risk of premenopausal breast cancer among Latin American women: results from the PRECAMA study.

Sci Rep 2020 02 10;10(1):2294. Epub 2020 Feb 10.

Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.

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 = 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.
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http://dx.doi.org/10.1038/s41598-020-59056-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010745PMC
February 2020

Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate With Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses.

Gastroenterology 2020 04 27;158(5):1300-1312.e20. Epub 2019 Dec 27.

Department of Cancer Biology and Genetics and the Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.

Background & Aims: Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development.

Methods: Serum levels of IGF1 were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls]) RESULTS: After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05-1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03-1.12; P = 3.3 × 10). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06-1.18; P = 4.2 × 10). Colorectal cancer risk was associated with only 1 variant in the IGFBP3 gene region (rs11977526), which also associated with anthropometric traits and circulating level of IGF2.

Conclusions: In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis.
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http://dx.doi.org/10.1053/j.gastro.2019.12.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152801PMC
April 2020

Project profile: a multicenter study on breast cancer in young women in Latin America (PRECAMA study).

Salud Publica Mex 2019 Sep-Oct;61(5):601-608

Section of Nutrition and Metabolism, International Agency for Research on Cancer. Lyon, France.

Objective: To describe the rationale and the methodology of a multicenter project to study the etiology of breast cancer in young Latin American women.

Materials And Methods: The International Agency for Research on Cancer has established an international collaborative population-based case-control study in four countries in Latin America: Chile, Colombia, Costa Rica, and Mexico (the PRECAMA study). Standardized methodologies were developed to collect information on reproductive variables, lifestyle, anthropometry, diet, clinical and pathological data, and biological specimens. The study will be extended to other countries in the region.

Conclusions: PRECAMA is unique in its multidisciplinary approach that combines genetics, genomics, and metabolomics with lifestyle factors. Then data generated through this project will be instrumental to identify major risk factors for molecular subtypes of breast cancer in young women, which will be important for pre- vention and targeted screening programs in Latin America.
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http://dx.doi.org/10.21149/10466DOI Listing
April 2020

Predicted basal metabolic rate and cancer risk in the European Prospective Investigation into Cancer and Nutrition.

Int J Cancer 2020 08 23;147(3):648-661. Epub 2019 Nov 23.

Diet, Genes and Environment, Danish Cancer Society Research Center, København, Denmark.

Emerging evidence suggests that a metabolic profile associated with obesity may be a more relevant risk factor for some cancers than adiposity per se. Basal metabolic rate (BMR) is an indicator of overall body metabolism and may be a proxy for the impact of a specific metabolic profile on cancer risk. Therefore, we investigated the association of predicted BMR with incidence of 13 obesity-related cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC). BMR at baseline was calculated using the WHO/FAO/UNU equations and the relationships between BMR and cancer risk were investigated using multivariable Cox proportional hazards regression models. A total of 141,295 men and 317,613 women, with a mean follow-up of 14 years were included in the analysis. Overall, higher BMR was associated with a greater risk for most cancers that have been linked with obesity. However, among normal weight participants, higher BMR was associated with elevated risks of esophageal adenocarcinoma (hazard ratio per 1-standard deviation change in BMR [HR ]: 2.46; 95% CI 1.20; 5.03) and distal colon cancer (HR : 1.33; 95% CI 1.001; 1.77) among men and with proximal colon (HR : 1.16; 95% CI 1.01; 1.35), pancreatic (HR : 1.37; 95% CI 1.13; 1.66), thyroid (HR : 1.65; 95% CI 1.33; 2.05), postmenopausal breast (HR : 1.17; 95% CI 1.11; 1.22) and endometrial (HR : 1.20; 95% CI 1.03; 1.40) cancers in women. These results indicate that higher BMR may be an indicator of a metabolic phenotype associated with risk of certain cancer types, and may be a useful predictor of cancer risk independent of body fatness.
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http://dx.doi.org/10.1002/ijc.32753DOI Listing
August 2020

Plasma polyphenols associated with lower high-sensitivity C-reactive protein concentrations: a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Br J Nutr 2020 01;123(2):198-208

CIBER de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain.

Experimental studies have reported on the anti-inflammatory properties of polyphenols. However, results from epidemiological investigations have been inconsistent and especially studies using biomarkers for assessment of polyphenol intake have been scant. We aimed to characterise the association between plasma concentrations of thirty-five polyphenol compounds and low-grade systemic inflammation state as measured by high-sensitivity C-reactive protein (hsCRP). A cross-sectional data analysis was performed based on 315 participants in the European Prospective Investigation into Cancer and Nutrition cohort with available measurements of plasma polyphenols and hsCRP. In logistic regression analysis, the OR and 95 % CI of elevated serum hsCRP (>3 mg/l) were calculated within quartiles and per standard deviation higher level of plasma polyphenol concentrations. In a multivariable-adjusted model, the sum of plasma concentrations of all polyphenols measured (per standard deviation) was associated with 29 (95 % CI 50, 1) % lower odds of elevated hsCRP. In the class of flavonoids, daidzein was inversely associated with elevated hsCRP (OR 0·66, 95 % CI 0·46, 0·96). Among phenolic acids, statistically significant associations were observed for 3,5-dihydroxyphenylpropionic acid (OR 0·58, 95 % CI 0·39, 0·86), 3,4-dihydroxyphenylpropionic acid (OR 0·63, 95 % CI 0·46, 0·87), ferulic acid (OR 0·65, 95 % CI 0·44, 0·96) and caffeic acid (OR 0·69, 95 % CI 0·51, 0·93). The odds of elevated hsCRP were significantly reduced for hydroxytyrosol (OR 0·67, 95 % CI 0·48, 0·93). The present study showed that polyphenol biomarkers are associated with lower odds of elevated hsCRP. Whether diet rich in bioactive polyphenol compounds could be an effective strategy to prevent or modulate deleterious health effects of inflammation should be addressed by further well-powered longitudinal studies.
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http://dx.doi.org/10.1017/S0007114519002538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015881PMC
January 2020

Prospective analysis of circulating metabolites and breast cancer in EPIC.

BMC Med 2019 09 24;17(1):178. Epub 2019 Sep 24.

Department of Community Medicine, UiT the Arctic University of Norway, Tromso, Norway.

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.
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http://dx.doi.org/10.1186/s12916-019-1408-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757362PMC
September 2019

Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition.

Int J Cancer 2020 06 10;146(12):3267-3280. Epub 2019 Oct 10.

CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992-2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00-1.26), with no detected heterogeneity across countries (p = 0.42). This risk increased linearly with duration of use (p = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97-1.43), which was heterogeneous across countries (p = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.
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http://dx.doi.org/10.1002/ijc.32674DOI Listing
June 2020

Prediagnostic Plasma Bile Acid Levels and Colon Cancer Risk: A Prospective Study.

J Natl Cancer Inst 2020 05;112(5):516-524

Hellenic Health Foundation, Athens, Greece.

Background: Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans.

Methods: Associations between prediagnostic plasma levels of 17 primary, secondary, and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations.

Results: Positive associations were observed between colon cancer risk and plasma levels of seven conjugated bile acid metabolites: the primary bile acids glycocholic acid (ORquartile 4 vs quartile 1= 2.22, 95% confidence interval [CI] = 1.52 to 3.26), taurocholic acid (OR = 1.78, 95% CI = 1.23 to 2.58), glycochenodeoxycholic acid (OR = 1.68, 95% CI = 1.13 to 2.48), taurochenodeoxycholic acid (OR = 1.62, 95% CI = 1.11 to 2.36), and glycohyocholic acid (OR = 1.65, 95% CI = 1.13 to 2.40), and the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95% CI = 1.12 to 2.54) and taurodeoxycholic acid (OR = 1.54, 95% CI = 1.02 to 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk.

Conclusions: This prospective study showed that prediagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.
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http://dx.doi.org/10.1093/jnci/djz166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225675PMC
May 2020

Polyphenol intake and differentiated thyroid cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Int J Cancer 2020 04 7;146(7):1841-1850. Epub 2019 Aug 7.

Department of Surgery, Skåne University Hospital Malmö, Lund University, Lund, Sweden.

Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow-up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country-specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC (HR = 0.99, 95% confidence interval [CI] 0.77-1.29), papillary (HR = 1.06, 95% CI 0.80-1.41) or follicular TC (HR = 1.10, 95% CI 0.55-2.22) were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols (p-trend = 0.019) and phenolic acids (p-trend = 0.007) and differentiated TC risk in subjects with BMI ≥ 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals.
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http://dx.doi.org/10.1002/ijc.32589DOI Listing
April 2020
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