Publications by authors named "Isabelle Romieu"

391 Publications

Adherence to the South African Food Based Dietary Guidelines may reduce breast cancer risk in black South African women: The SABC study.

Public Health Nutr 2021 Nov 29:1-39. Epub 2021 Nov 29.

Nutrition and Metabolism Branch, International Agency for Research on Cancer - WHO, 150 cours Albert Thomas, 69372, 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 (SAFBDGs) 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 SAFBDGs, a 9-point adherence score (out of 11 guidelines) was developed, using suggested adherence cut-points for scoring each recommendation (0 and 1). When the association between higher adherence to the SAFBDGs and breast cancer risk were assessed, data driven tertiles among controls were used as cut-points for scoring each recommendation (0, 0.5 and 1). Odds ratios and 95% confidence intervals were estimated using multivariate logistic regression models.

Setting: Soweto, South Africa.

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

Results: After adjusting for potential confounders, higher adherence (>5.0) to the SAFBDGs vs. 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 SAFBDGs.

Conclusions: Higher adherence to the SAFBDGs may reduce breast cancer risk in this population.The concerning low levels of adherence to the SAFBDGs emphasize the need for education campaigns and to create healthy food environments in South Africa to increase adherence to the SAFBDGs.
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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

Modification of the association by sex between the prenatal exposure to di(2-ethylhexyl) phthalate and fat percentage in a cohort of Mexicans schoolchildren.

Int J Obes (Lond) 2021 Sep 20. Epub 2021 Sep 20.

Instituto Nacional de Salud Pública, Dirección de Salud Ambiental, Cuernavaca, MOR, Mexico.

Introduction: Children's overweight and obesity are global public health problems, children with obesity have grater obesity risk as adults, thus leading to develop cardiometabolic diseases. Previous studies have found positive and significant associations between the exposure to phthalates and body mass index and body composition.

Objective: To evaluate the modification of the association by sex between DEHP exposure during pregnancy and the percentage of body fat in a cohort of Mexican schoolchildren.

Material And Methods: The sample was comprised by children which had previously participated in a POSGRAD longitudinal study. A subsample of 190 mother-children binomials were included. Mothers' DEHP concentrations and its metabolites had been measured in the second trimester of pregnancy: Mono-2-ethylhexyl phthalate (MEHP), Mono-2-ethyl-5-carboxypentyl phthalate (MECPP), Mono-2-ethyl-5-hidroxyhexyl phthalate (MEHHP), and Mono-2-ethyl-5-oxohexyl phthalate (MEOHP). The children's adipose mass was measured at age 8, 9, and 10. Longitudinal data were analyzed using the mixed effects linear regression model, with intercept and random slope, adjusted by important confounders and stratified by sex.

Results: We found a differentiated effect by sex, the exposure to DEHP during pregnancy significantly increases the adipose mass in boys. The average increase was 0.058% (p = 0.02) for every 1% variation in MECPP; 0.047% (p = 0.04) in MEHHP; 0.051% (p = 0.03) in MEOHP, and 0.066% (p = 0.007) in MECPP.

Conclusions: The results suggest an effect differentiated by sex; with boys being the main ones affected by the prenatal exposure to phthalates. However, we cannot rule out effects in girls.
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http://dx.doi.org/10.1038/s41366-021-00952-wDOI Listing
September 2021

Maternal FADS2 single nucleotide polymorphism modified the impact of prenatal docosahexaenoic acid (DHA) supplementation on child neurodevelopment at 5 years: Follow-up of a randomized clinical trial.

Clin Nutr 2021 10 11;40(10):5339-5345. Epub 2021 Sep 11.

Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA. Electronic address:

Background: Variability in the FADS2 gene, which codifies the Delta-6 Desaturases and modulates the conversion of essential n-3 and n-6 fatty acids into long-chain polyunsaturated fatty acids, might modify the impact of prenatal supplementation with n-3 docosahexaenoic acid (DHA) on neurodevelopment.

Objective: To assess if maternal FADS2 single nucleotide polymorphisms (SNPs) modified the effect of prenatal DHA on offspring development at 5 years.

Design: We conducted a post-hoc interaction analysis of the POSGRAD randomized controlled trial (NCT00646360) of prenatal supplementation with algal-DHA where 1094 pregnant women originally randomized to 400 mg/day of preformed algal DHA or a placebo from gestation week 18-22 through delivery. In this analysis, we included offspring with information on maternal genotype and neurodevelopment at 5 years (DHA = 316; Control = 306) and used generalized linear models to assess interactions between FADS2 SNPs rs174602 or rs174575 and prenatal DHA on neurodevelopment at 5 years measured with McCarthy Scales of Children's Abilities (MSCA).

Results: Maternal and offspring characteristics were similar between groups. At baseline, mean (±standard deviation) maternal age was 26 ± 5 years and schooling was 12 ± 4 years. Forty-six percent (46%) of the children were female. Maternal minor allele frequencies were 0.37 and 0.33 for SNPs rs174602 and rs174575, respectively. There were significant variations by SNP rs174602 and intervention group (p for interactions <0.05) where children in the intervention group had higher MSCA scores on the quantitative (DHA: mean ± SEM = 22.6 ± 0.9 vs. Control = 19.1 ± 0.9, mean difference (Δ) = 3.45; p = 0.01) and memory (DHA = 27.9 ± 1.1 vs. Control = 23.7 ± 1.1, Δ = 4.26; p = 0.02) scales only among offspring of TT (minor allele homozygotes).

Conclusions: Maternal FADS2 SNP rs174602 modified the effect of prenatal DHA on cognitive development at 5 years. Variations in the genetic make-up of target populations could be an important factor to consider for prenatal DHA supplementation interventions.
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http://dx.doi.org/10.1016/j.clnu.2021.08.026DOI Listing
October 2021

Infant Metabolome in Relation to Prenatal DHA Supplementation and Maternal Single-Nucleotide Polymorphism rs174602: Secondary Analysis of a Randomized Controlled Trial in Mexico.

J Nutr 2021 Nov;151(11):3339-3349

Doctoral Program in Nutrition and Health Sciences, Laney Graduate School, Emory University, Atlanta, GA, USA.

Background: Although DHA (22:6n-3) is critical for fetal development, results from randomized controlled trials (RCTs) of prenatal DHA supplementation report inconsistent effects on offspring health. Variants in fatty acid desaturase (FADS) genes that regulate the conversion of n-3 and n-6 essential fatty acids into their biologically active derivatives may explain this heterogeneity.

Objectives: We investigated the effect of prenatal DHA supplementation on the offspring metabolome at age 3 mo and explored differences by maternal FADS single-nucleotide polymorphism (SNP) rs174602.

Methods: Data were obtained from a double-blind RCT in Mexico [POSGRAD (Prenatal Omega-3 Fatty Acid Supplementation and Child Growth and Development)] in which women (18-35 y old) received DHA (400 mg/d) or placebo from mid-gestation until delivery. Using high-resolution MS with LC, untargeted metabolomics was performed on 112 offspring plasma samples. Discriminatory metabolic features were selected via linear regression (P < 0.05) with false discovery rate (FDR) correction (q = 0.2). Interaction by SNP rs174602 was assessed using 2-factor ANOVA. Stratified analyses were performed, where the study population was grouped into carriers (TT, TC; n = 70) and noncarriers (CC; n = 42) of the minor allele. Pathway enrichment analysis was performed with Mummichog (P < 0.05).

Results: After FDR correction, there were no differences in metabolic features between infants whose mothers received prenatal DHA (n = 58) and those whose mothers received placebo (n = 54). However, we identified 343 differentially expressed features in the interaction analysis after FDR correction. DHA supplementation positively enriched amino acid and aminosugars metabolism pathways and decreased fatty acid metabolism pathways among offspring of minor allele carriers and decreased metabolites within the tricarboxylic acid cycle and galactose metabolism pathways among offspring of noncarriers.

Conclusions: Our findings demonstrate differences in infant metabolism in response to prenatal DHA supplementation by maternal SNP rs174602 and further support the need to incorporate genetic analysis of FADS polymorphisms into DHA supplementation trials.This trial was registered at clinicaltrials.gov as NCT00646360.
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http://dx.doi.org/10.1093/jn/nxab276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8562085PMC
November 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

[Impact of nutritional factors during and after cancer].

Bull Cancer 2021 May 6;108(5):455-464. Epub 2021 Apr 6.

Cellule de coordination, domaine de Vilvert, réseau national alimentation cancer recherche (Réseau NACRe), 78350 Jouy-en-Josas, France.

Nutritional factors (diet, weight, alcohol, physical activity) are identified as factors having an impact on the onset of several cancer sites. Less abundant scientific data also underline their impact on the tumor progression. A review of the scientific literature was carried out by a group of experts established by the French National Cancer Institute (INCa) to better document the influence of nutritional factors during and after cancer on outcomes such as overall mortality, cancer specific mortality, recurrence, second primary cancers and quality of life. This analysis of the literature completes messages of reduction of alcohol consumption, prevention of undernutrition or excess weight and adherence to dietary recommendations, avoiding the use of dietary supplements, fasting or restrictive diets and strengthens messages promoting the practice of physical activity and the fight against sedentary lifestyle.
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http://dx.doi.org/10.1016/j.bulcan.2021.03.001DOI Listing
May 2021

Prevalent diabetes and risk of total, colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium.

Br J Cancer 2021 May 26;124(11):1882-1890. Epub 2021 Mar 26.

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

Background: We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity.

Methods: We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis.

Results: A total of 667,916 individuals were included with an overall median (P25-P75) age at recruitment of 62.3 (57-67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86-1.04; I = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08-1.26; I = 0%) and a similar HR in women (1.13; 95% CI: 0.82-1.56; I = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77-0.85; I = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89-1.03; I = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity.

Conclusions: Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.
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http://dx.doi.org/10.1038/s41416-021-01347-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144608PMC
May 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

Body mass index and waist circumference in relation to the risk of 26 types of cancer: a prospective cohort study of 3.5 million adults in Spain.

BMC Med 2021 01 14;19(1):10. Epub 2021 Jan 14.

Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Gran Via Corts Catalanes, 587 àtic, 08007, Barcelona, Spain.

Background: A high body mass index (BMI) has been associated with increased risk of several cancers; however, whether BMI is related to a larger number of cancers than currently recognized is unclear. Moreover, whether waist circumference (WC) is more strongly associated with specific cancers than BMI is not well established. We aimed to investigate the associations between BMI and 26 cancers accounting for non-linearity and residual confounding by smoking status as well as to compare cancer risk estimates between BMI and WC.

Methods: Prospective cohort study with population-based electronic health records from Catalonia, Spain. We included 3,658,417 adults aged ≥ 18 years and free of cancer at baseline between 2006 and 2017. Our main outcome measures were cause-specific hazard ratios (HRs) with 99% confidence intervals (CIs) for incident cancer at 26 anatomical sites.

Results: After a median follow-up time of 8.3 years, 202,837 participants were diagnosed with cancer. A higher BMI was positively associated with risk of nine cancers (corpus uteri, kidney, gallbladder, thyroid, colorectal, breast post-menopausal, multiple myeloma, leukemia, non-Hodgkin lymphoma) and was positively associated with three additional cancers among never smokers (head and neck, brain and central nervous system, Hodgkin lymphoma). The respective HRs (per 5 kg/m increment) ranged from 1.04 (99%CI 1.01 to 1.08) for non-Hodgkin lymphoma to 1.49 (1.45 to 1.53) for corpus uteri cancer. While BMI was negatively associated to five cancer types in the linear analyses of the overall population, accounting for non-linearity revealed that BMI was associated to prostate cancer in a U-shaped manner and to head and neck, esophagus, larynx, and trachea, bronchus and lung cancers in an L-shaped fashion, suggesting that low BMIs are an approximation of heavy smoking. Of the 291,305 participants with a WC measurement, 27,837 were diagnosed with cancer. The 99%CIs of the BMI and WC point estimates (per 1 standard deviation increment) overlapped for all cancers.

Conclusions: In this large Southern European study, a higher BMI was associated with increased risk of twelve cancers, including four hematological and head and neck (only among never smokers) cancers. Furthermore, BMI and WC showed comparable estimates of cancer risk associated with adiposity.
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http://dx.doi.org/10.1186/s12916-020-01877-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807518PMC
January 2021

Pro-Inflammatory Diet Is Associated with Adiposity during Childhood and with Adipokines and Inflammatory Markers at 11 Years in Mexican Children.

Nutrients 2020 Nov 27;12(12). Epub 2020 Nov 27.

Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.

There is limited evidence about the inflammatory potential of diet in children. The aim of this study was to evaluate the association between the Children's Dietary Inflammatory Index (C-DII) from 5 to 11 years with adiposity and inflammatory biomarkers in Mexican children. We analyzed 726 children from a birth cohort study with complete dietary information and measurements to evaluate adiposity at 5, 7 and 11 y and 286 children with IL-6, hsCRP, leptin and adiponectin information at 11 y. C-DII trajectories were estimated using latent class linear mixed models. We used linear mixed models for adiposity and logistic and multinomial regression for biomarkers. In girls, each one-point increase in C-DII score was associated with greater adiposity (abdominal-circumference 0.41%, = 0.03; skinfold-sum 1.76%, = 0.01; and BMI Z-score 0.05, = 0.01). At 11 y the C-DII was associated with greater leptin (34% ≥ 13.0 ng/mL, = 0.03) and hsCRP concentrations (29% ≥ 3.00 mg/L, = 0.06) and lower adiponectin/leptin ratio (75% < 2.45, = 0.02). C-DII trajectory 3 in boys was associated with a 75.2% ( < 0.01) increase in leptin concentrations and a 37.9% decrease ( = 0.02) in the adiponectin/leptin ratio. This study suggests that the inflammatory potential of diet may influence adiposity in girls and the homeostasis of adipose tissue and chronic subclinical inflammation in 11-year-old children.
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http://dx.doi.org/10.3390/nu12123658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760203PMC
November 2020

Serum Phospholipid Fatty Acids Levels, Anthropometric Variables and Adiposity in Spanish Premenopausal Women.

Nutrients 2020 Jun 25;12(6). Epub 2020 Jun 25.

Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, 28029 Madrid, Spain.

This study investigates the still uncertain association between serum phospholipid fatty acids (PL-FA), and anthropometric and adiposity variables. A cross-sectional study was conducted with 1443 Spanish premenopausal women. Participants answered an epidemiological and a food frequency questionnaire. Anthropometric variables were measured using a bioimpedance scale. Serum PL-FAs levels were determined by gas chromatography-mass spectrometry. The association between body mass index (BMI), weight gain, body fat percentage, visceral fat index, and waist circumference with serum PL-FAs and desaturation indices was evaluated using multivariable linear regression models. BMI was positively associated with the relative concentration of saturated fatty acids (SFAs) (β = 0.94, q-val = 0.001), and with palmitoleic, dihomo-γ-linolenic (DGLA), arachidonic (AA) and α-linolenic acids, and was inversely associated with oleic, gondoic, trans-vaccenic, linoleic and γ-linolenic acids. Total fat percentage was positively associated with DGLA and AA, and inversely with linoleic and γ-linolenic acids. Low relative concentrations of some SFAs and high levels of n-6 PUFAs were associated with greater waist circumference. While the oleic/stearic and AA/DGLA acid ratios were inversely associated with BMI, DGLA/linoleic acid ratio was positively related to almost all variables. In addition to BMI, total fat percentage and waist circumference were also associated with certain individual fatty acids.
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http://dx.doi.org/10.3390/nu12061895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353394PMC
June 2020

Serum Phospholipid Fatty Acids and Mammographic Density in Premenopausal Women.

J Nutr 2020 09;150(9):2419-2428

Cancer and Environmental Epidemiology Unit, Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.

Background: The role of fatty acids (FAs) on mammographic density (MD) is unclear, and available studies are based on self-reported dietary intake.

Objectives: This study assessed the association between specific serum phospholipid fatty acids (PLFAs) and MD in premenopausal women.

Methods: The cross-sectional study DDM-Madrid recruited 1392 Spanish premenopausal women, aged 39-50 y, who attended a screening in a breast radiodiagnosis unit of Madrid City Council. Women completed lifestyle questionnaires and FFQs. Percentage MD was estimated using a validated computer tool (DM-Scan), and serum PLFA percentages were measured by GC-MS. Multivariable linear regression models were used to quantify the association of FA tertiles with MD. Models were adjusted for age, education, BMI, waist circumference, parity, oral contraceptive use, previous breast biopsies, and energy intake, and they were corrected for multiple testing.

Results: Women in the third tertile of SFAs showed significantly higher MD compared with those in the first tertile (βT3vsT1 = 7.53; 95% CI: 5.44, 9.61). Elevated relative concentrations of palmitoleic (βT3vsT1 = 3.12; 95% CI: 0.99, 5.25) and gondoic (βT3vsT1 = 2.67; 95% CI: 0.57, 4.77) MUFAs, as well as high relative concentrations of palmitelaidic (βT3vsT1 = 5.22; 95% CI: 3.15, 7.29) and elaidic (βT3vsT1 = 2.69; 95% CI: 0.59, 4.79) trans FAs, were also associated with higher MD. On the contrary, women with elevated relative concentrations of n-6 (ω-6) linoleic (βT3vsT1 = -5.49; 95% CI; -7.62, -3.35) and arachidonic (βT3vsT1 = -4.68; 95% CI: -6.79, -2.58) PUFAs showed lower MD. Regarding desaturation indices, an elevated palmitoleic to palmitic ratio and a low ratio of oleic to steric and arachidonic to dihomo-γ-linolenic acids were associated with higher MD.

Conclusions: Spanish premenopausal women with high relative concentrations of most SFAs and some MUFAs and trans FAs showed an increased MD, whereas those with high relative concentrations of some n-6 PUFAs presented lower density. These results, which should be confirmed in further studies, underscore the importance of analyzing serum FAs individually.
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http://dx.doi.org/10.1093/jn/nxaa168DOI Listing
September 2020

Prenatal exposure to VOCs and NOx and lung function in preschoolers.

Pediatr Pulmonol 2020 08 25;55(8):2142-2149. Epub 2020 Jun 25.

Departamento de Salud Ambiental, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico.

Background: Several studies have shown that exposure to air pollutants affects lung growth and development and can result in poor respiratory health in early life.

Methods: We included a subsample of 772 Mexican preschoolers whose mothers participated in a Prenatal Omega-3 fatty acid Supplements, GRowth, And Development birth cohort study with the aim to evaluate the impact of prenatal exposure to volatile organic compounds and nitrogen oxides on lung function measured by oscillation tests. The preschoolers were followed until 5 years of age. Anthropometric measurements and forced oscillation tests were performed at 36, 48, and 60 months of age. Information on sociodemographic and health characteristics was obtained during follow up. Prenatal exposure to volatile organic compounds and nitrogen oxides was evaluated using a land use regression models and the association between them was tested using a lineal regression and longitudinal linear mixed effect models adjusting for potential confounders.

Results: Overall, the mean (standard deviation) of the measurements of respiratory system resistance and respiratory system reactance at 6, 8, and 10 Hz during the follow-up period was 11.3 (2.4), 11.1 (2.4), 10.3 (2.2) and -5.2 (1.6), -4.8 (1.7), and -4.6 hPa s L (1.6), respectively. We found a significantly positive association between respiratory resistance (β  = 0.011; 95%CI: 0.001, 0.023) (P < .05) and prenatal exposure to nitrogen dioxide and a marginally negatively association between respiratory reactance (β  = -11.40 95%CI: -25.26, 1.17 and β  = -11.91 95%CI: -26.51, 1.43) (P = .07) and prenatal exposure to xylene.

Conclusion: Prenatal exposure to air pollutants was significantly associated with the alteration of lung function measured by oscillation tests in these preschool children.
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http://dx.doi.org/10.1002/ppul.24889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485223PMC
August 2020

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

Latin American Study of Hereditary Breast and Ovarian Cancer : A Genomic Epidemiology Approach.

Front Oncol 2019 20;9:1429. Epub 2019 Dec 20.

Departamento de Investigación, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru.

Hereditary Breast and Ovarian Cancer (HBOC) syndrome is responsible for ~5-10% of all diagnosed breast and ovarian cancers. Breast cancer is the most common malignancy and the leading cause of cancer-related mortality among women in Latin America (LA). The main objective of this study was to develop a comprehensive understanding of the genomic epidemiology of HBOC throughout the establishment of The Latin American consortium for HBOC-LACAM, consisting of specialists from 5 countries in LA and the description of the genomic results from the first phase of the study. We have recruited 403 individuals that fulfilled the criteria for HBOC from 11 health institutions of Argentina, Colombia, Guatemala, Mexico and Peru. A pilot cohort of 222 individuals was analyzed by NGS gene panels. One hundred forty-three genes were selected on the basis of their putative role in susceptibility to different hereditary cancers. Libraries were sequenced in MiSeq (Illumina, Inc.) and PGM (Ion Torrent-Thermo Fisher Scientific) platforms. The overall prevalence of pathogenic variants was 17% (38/222); the distribution spanned 14 genes and varied by country. The highest relative prevalence of pathogenic variants was found in patients from Argentina (25%, 14/57), followed by Mexico (18%, 12/68), Guatemala (16%, 3/19), and Colombia (13%, 10/78). Pathogenic variants were found in (20%) and (29%) genes. Pathogenic variants were found in other 12 genes, including high and moderate risk genes such as , and . Additional pathogenic variants were found in HBOC unrelated genes such as , and . In this first phase of the project, we recruited 403 individuals and evaluated the germline genetic alterations in an initial cohort of 222 patients among 4 countries. Our data show for the first time in LA the distribution of pathogenic variants in a broad set of cancer susceptibility genes in HBOC. Even though we used extended gene panels, there was still a high proportion of patients without any detectable pathogenic variant, which emphasizes the larger, unexplored genetic nature of the disease in these populations.
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http://dx.doi.org/10.3389/fonc.2019.01429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933010PMC
December 2019

Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study.

BMC Med 2020 01 10;18(1). Epub 2020 Jan 10.

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

Background: Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases.

Methods: In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs.

Results: During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles.

Conclusion: Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
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http://dx.doi.org/10.1186/s12916-019-1474-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953215PMC
January 2020

Synergistic action of folate intake and testosterone associated with breast cancer risk.

Nutr Res 2019 11 23;71:100-110. Epub 2019 Oct 23.

Population Health Research Center, National Institute of Public Health, Avenida Universidad No. 655, Colonia Santa María Ahuacatitlán, Cuernavaca, Morelos 62100, Mexico. Electronic address:

The amount of irreparable DNA damage is a function of the rate of cell division, and the association between sex hormones and the risk of breast cancer has been explained by an increase in cell division. Folate intake insufficiency leads to disturbances in DNA replication and DNA repair. We hypothesized that folate intake insufficiency and high serum concentrations of sex hormones act synergistically on the risk of breast cancer. The aim of this study was to investigate the interaction between sex hormones (exposure of interest A) and dietary folate intake (exposure of interest B) on the risk of breast cancer. We included 342 breast cancer primary postmenopausal cases and 294 controls obtained from a large population-based case-control study. Multiple conditional logistic regression models were used for the analysis and interactions were tested. The joint effect of the lowest dietary folate intake (T1 < 259.40 mg/d) and the highest serum concentration of testosterone (T3 ≥ 0.410 on the risk of breast cancer was odds ratio = 9.18 (95% confidence interval 2.56-32.88) when compared to the lowest-risk category, namely, the group of women with the highest dietary folate intake (T3 > 381.29 mg/d) and the lowest serum concentration of testosterone (T1 ≤ 0.25 pg/mL). There were some indications that the estimated join effect was greater than the product of the estimated effects alone (P = .001). These findings have important public health implications with respect to reducing the risk of the most frequent cancer in women worldwide.
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http://dx.doi.org/10.1016/j.nutres.2019.10.002DOI Listing
November 2019

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

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

Comparison of smoking-related DNA methylation between newborns from prenatal exposure and adults from personal smoking.

Epigenomics 2019 10 19;11(13):1487-1500. Epub 2019 Sep 19.

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for exposure in newborns is unknown. We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring.
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http://dx.doi.org/10.2217/epi-2019-0066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836223PMC
October 2019

Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations.

Nutrients 2019 08 20;11(8). Epub 2019 Aug 20.

CIBER Epidemiology and Public Healh (CIBERESP), Madrid 28029, Spain.

Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the , , and genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (, and ). However, none of these SNPs were statistically significant after Benjamini-Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor β (TGFβ) signaling was associated with CRC risk ( ≤ 0.001), with most statistically significant genes being = 0.008) and = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites ( = 0.036). The 25(OH)D-gene pathway analysis suggested that genetic variants in the genes related to VDR complex formation and transcriptional activity are associated with CRC depending on 25(OH)D levels (interaction = 0.041). Additional studies in large populations and consortia, especially with measured circulating 25(OH)D, are needed to confirm our findings.
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http://dx.doi.org/10.3390/nu11081954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722852PMC
August 2019

Occupation and risk of female breast cancer: A case-control study in Morocco.

Am J Ind Med 2019 10 5;62(10):838-846. Epub 2019 Aug 5.

IFSTTAR, UMRESTTE, UCBL, University of Lyon, Lyon, France.

Background: Breast cancer is the most frequent cancer among Moroccan women. Environmental and occupational factors may play a role in breast cancer etiology. This study aimed to investigate the association between occupation, industry, and breast cancer risk among Moroccan women.

Methods: A total of 300 breast cancer cases and 300 controls (matched by age and area of residence) were included in this study. Full occupational history was collected, with a detailed description of each job held for at least 6 months. Occupations were coded according to the International Standard Classification of Occupations (ISCO 08) and the Moroccan Analytical Classification of Professions (2001). Industries were coded according to the Statistical Classification of Economic Activities in the European Community (2008). Odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounders were estimated by using conditional logistic regression.

Results: An overall decreased risk of breast cancer was observed among women doing only household work (OR = 0.32; 95% CI = 0.18-0.55). An increased risk of breast cancer was observed among women in agricultural occupations, particularly those employed as agricultural laborers (ISCO 08 code: 921; OR = 2.91; 95% CI = 1.51-5.60) and the risk increased with duration of employment (P trend = .01). Analyses by industry corroborated these findings.

Conclusions: Our findings suggest that occupational exposures may be associated with increased risk of breast cancer among female agricultural workers in this population. Further investigations, with advanced methods of occupational exposure assessment, are warranted to clarify the role of chemicals involved in this high-risk occupation and to suggest preventive actions and screening.
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http://dx.doi.org/10.1002/ajim.23027DOI Listing
October 2019

A follow-up study after an improved cookstove intervention in rural Mexico: Estimation of household energy use and chronic PM exposure.

Environ Int 2019 10 25;131:105013. Epub 2019 Jul 25.

Environmental Health Department, Centre for Population Health Research, National Institute of Public Health (INSP), Cuernavaca, Morelos, Mexico; Hubert Department of Global Health, Emory University, Atlanta, GA, USA.

The benefits of improved biomass cookstoves (ICS) depends on their adoption and sustained use. Few studies have documented if and how they are used more than five years after being introduced. We conducted a 9-year prospective cohort study among young rural women in the highlands of Michoacan, Mexico. Participants had received a Patsari ICS during a community trial either in 2005 or 2006. With retrospective information collected in 2012-13, we studied the households' energy use, ICS survival, and cooking practices during the follow-up period. Using an exposure model constructed with personal PM measurements in a subsample of homes at the time of the initial trial in 2005, we estimated the exposure associated with different energy use patterns during the follow-up period. The ICS had a mean lifespan of 4 years, after which more than half of the stoves were not in use; therefore, the use of open fire increased, particularly among the indigenous communities. ICS use peak was achieved two years after the initial trial, either exclusively or combined with open fire. Yearly household energy use and other variables were used to estimate chronic air pollution exposure. Mean PM exposure during the follow-up period ranged from 51 to 319 μg/m; the median was 102 and 146 μg/m for mainly ICS and mainly open fire use, respectively. The ICS has a useful period after which it needs maintenance, repair, or replacement. Unfortunately, many programs have not afforded a follow-up component. Exposure to biomass smoke air pollutants can be reduced by using an ICS instead of the traditional open fire. Household energy strategies should ensure equitable access to clean energy options adapted to local needs and preferences with culturally appropriate technology implemented on a sustainable perspective.
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http://dx.doi.org/10.1016/j.envint.2019.105013DOI Listing
October 2019

Short- and long-term impact of adapted physical activity and diet counseling during adjuvant breast cancer therapy: the "APAD1" randomized controlled trial.

BMC Cancer 2019 Jul 25;19(1):737. Epub 2019 Jul 25.

Val d'Aurelle Montpellier Cancer Institute (ICM), 208, Avenue des Apothicaires, Parc Euromédecine, 34298 Montpellier Cedex 5, France; Montpellier University, 34000, Montpellier, France.

Background: Patients with breast cancer undergoing chemotherapy and radiotherapy experience fatigue and other treatment side effects. Integrative therapies combining physical activity and dietary counseling are recommended; however to date no large randomized controlled trial has been conducted during adjuvant therapy. The Adapted Physical Activity and Diet (APAD) intervention was evaluated for its ability to decrease fatigue (primary outcome), anxiety, depression, body mass index (BMI), and fat mass, and enhance muscular and cognitive performances, and quality-of-life (QoL).

Methods: Women diagnosed with early breast cancer (N = 143, mean age = 52 ± 10 years) were randomized to APAD or usual care (UC). APAD included thrice-weekly moderate-intensity mixed aerobic and resistance exercise sessions and 9 dietetic consultations. Patient-reported outcomes (PROs) and anthropometric, muscular, and cognitive variables were measured at baseline, 18 weeks (end of chemotherapy), and 26 weeks (end of radiotherapy and intervention), and at 6- and 12-month post-intervention follow-ups. Multi-adjusted linear mixed-effects models were used to compare groups over time.

Results: Significant beneficial effects of the APAD intervention were observed on all PROs (i.e., fatigue, QoL, anxiety, depression) at 18 and 26 weeks. The significant effect on fatigue and QoL persisted up to 12-month follow-up. Significant decreases in BMI, fat mass, and increased muscle endurance and cognitive flexibility were observed at 26 weeks, but did not persist afterward. Leisure physical activity was enhanced in the APAD group vs UC group at 18 and 26 weeks. No significant effect of the intervention was found on major macronutrients intake.

Conclusions: A combined diet and exercise intervention during chemotherapy and radiotherapy in patients with early breast cancer led to positive changes in a range of psychological, physiological and behavioral outcomes at the end of intervention. A beneficial effect persisted on fatigue and QoL at long term, i.e., 1 year post-intervention. Diet-exercise supportive care should be integrated into the management of early breast cancer patients.

Trial Registration: The APAD study was prospectively registered on ClinicalTrials.gov (NCT01495650; date of registration: December 20, 2011).
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http://dx.doi.org/10.1186/s12885-019-5896-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659309PMC
July 2019

Blood DNA methylation and breast cancer risk: a meta-analysis of four prospective cohort studies.

Breast Cancer Res 2019 05 17;21(1):62. Epub 2019 May 17.

Divison of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA.

Background: Environmental and genetic factors play an important role in the etiology of breast cancer. Several small blood-based DNA methylation studies have reported risk associations with methylation at individual CpGs and average methylation levels; however, these findings require validation in larger prospective cohort studies. To investigate the role of blood DNA methylation on breast cancer risk, we conducted a meta-analysis of four prospective cohort studies, including a total of 1663 incident cases and 1885 controls, the largest study of blood DNA methylation and breast cancer risk to date.

Methods: We assessed associations with methylation at 365,145 CpGs present in the HumanMethylation450 (HM450K) Beadchip, after excluding CpGs that did not pass quality controls in all studies. Each of the four cohorts estimated odds ratios (ORs) and 95% confidence intervals (CI) for the association between each individual CpG and breast cancer risk. In addition, each study assessed the association between average methylation measures and breast cancer risk, adjusted and unadjusted for cell-type composition. Study-specific ORs were combined using fixed-effect meta-analysis with inverse variance weights. Stratified analyses were conducted by age at diagnosis (< 50, ≥ 50), estrogen receptor (ER) status (+/-), and time since blood collection (< 5, 5-10, > 10 years). The false discovery rate (q value) was used to account for multiple testing.

Results: The average age at blood draw ranged from 52.2 to 62.2 years across the four cohorts. Median follow-up time ranged from 6.6 to 8.4 years. The methylation measured at individual CpGs was not associated with breast cancer risk (q value > 0.59). In addition, higher average methylation level was not associated with risk of breast cancer (OR = 0.94, 95% CI = 0.85, 1.05; P = 0.26; P for study heterogeneity = 0.86). We found no evidence of modification of this association by age at diagnosis (P = 0.17), ER status (P = 0.88), time since blood collection (P = 0.98), or CpG location (P = 0.98).

Conclusions: Our data indicate that DNA methylation measured in the blood prior to breast cancer diagnosis in predominantly postmenopausal women is unlikely to be associated with substantial breast cancer risk on the HM450K array. Larger studies or with greater methylation coverage are needed to determine if associations exist between blood DNA methylation and breast cancer risk.
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http://dx.doi.org/10.1186/s13058-019-1145-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525390PMC
May 2019

Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk.

Clin Epigenetics 2019 04 30;11(1):66. Epub 2019 Apr 30.

International Agency for Research on Cancer (IARC), Lyon, France.

Background: It is well established that estrogens and other hormonal factors influence breast cancer susceptibility. We hypothesized that a woman's total lifetime estrogen exposure accumulates changes in DNA methylation, detectable in the blood, which could be used in risk assessment for breast cancer.

Methods: An estimated lifetime estrogen exposure (ELEE) model was defined using epidemiological data from EPIC-Italy (n = 31,864). An epigenome-wide association study (EWAS) of ELEE was performed using existing Illumina HumanMethylation450K Beadchip (HM450K) methylation data obtained from EPIC-Italy blood DNA samples (n = 216). A methylation index (MI) of ELEE based on 31 CpG sites was developed using HM450K data from EPIC-Italy and the Generations Study and evaluated for association with breast cancer risk in an independent dataset from the Generations Study (n = 440 incident breast cancer cases matched to 440 healthy controls) using targeted bisulfite sequencing. Lastly, a meta-analysis was conducted including three additional cohorts, consisting of 1187 case-control pairs.

Results: We observed an estimated 5% increase in breast cancer risk per 1-year longer ELEE (OR = 1.05, 95% CI 1.04-1.07, P = 3 × 10) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data (OR = 1.77, 95% CI 1.07-2.93, P = 0.027) and in the meta-analysis (OR = 1.43, 95% CI 1.05-2.00, P = 0.024); however, the correlation between the MI and ELEE was not validated across study cohorts.

Conclusion: We have identified a blood DNA methylation signature associated with breast cancer risk in this study. Further investigation is required to confirm the interaction between estrogen exposure and DNA methylation in the blood.
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http://dx.doi.org/10.1186/s13148-019-0664-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492393PMC
April 2019

Role of Leptin in the Association Between Body Adiposity and Persistent Asthma: A Longitudinal Study.

Obesity (Silver Spring) 2019 06 20;27(6):894-898. Epub 2019 Apr 20.

VIMA: Aging and Chronic Diseases, Epidemiological and Public Health Approaches, INSERM U1168, Villejuif, France.

Objective: Obesity is a likely risk factor for asthma. However, underlying mechanisms by which obesity affects asthma activity remain poorly understood. This study aimed to investigate the role of leptin, an adipocyte-derived proinflammatory protein, as a mediator in the association between body adiposity (assessed using BMI, waist circumference, and body fat percentage) and persistent asthma.

Methods: A causal approach to mediation analysis was used to disentangle total and direct effects and the indirect effect mediated by leptin, using data from the French prospective French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) (baseline: 2003-2007; follow-up: 2011-2013; mean follow-up time: 7 years). A total of 331 participants with current asthma at baseline were included.

Results: Per 1-SD increment in BMI, waist circumference, and body fat percentage, the adjusted odds ratios of the total effect were 1.59 (95% CI: 0.95-2.97), 2.06 (1.06-4.00), and 3.25 (1.01-9.41), respectively; the odds ratios of the indirect effect mediated by leptin were 1.68 (1.09-2.46), 1.55 (0.99-2.57), and 1.99 (0.94-4.83), respectively.

Conclusions: Leptin partly (> 60%) mediated the association between high body adiposity and persistent asthma over time. Using a newly developed analytic approach, this longitudinal study brought new insight into one mechanism by which obesity may affect asthma activity.
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http://dx.doi.org/10.1002/oby.22466DOI Listing
June 2019
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