Publications by authors named "Marie-Christine Boutron-Ruault"

558 Publications

Long-term exposure to air pollution and liver cancer incidence in six European cohorts.

Int J Cancer 2021 Jul 18. Epub 2021 Jul 18.

Section of Environmental Health, Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.

Particulate matter air pollution and diesel engine exhaust have been classified as carcinogenic for lung cancer, yet few studies have explored associations with liver cancer. We used six European adult cohorts which were recruited between 1985 and 2005, pooled within the 'Effects of low-level air pollution: A study in Europe' (ELAPSE) project, and followed for the incidence of liver cancer until 2011 to 2015. The annual average exposure to nitrogen dioxide (NO ), particulate matter with diameter < 2.5 μm (PM ), black carbon (BC), warm-season ozone (O ), and eight elemental components of PM (copper, iron, zinc, sulfur, nickel, vanadium, silicon, potassium) were estimated by European-wide hybrid land-use regression models at participants' residential addresses. We analyzed the association between air pollution and liver cancer incidence by Cox proportional hazards models adjusting for potential confounders. Of 330,064 cancer-free adults at baseline, 512 developed liver cancer during a mean follow-up of 18.1 years. We observed positive linear associations between NO (hazard ratio, 95% confidence interval: 1.17, 1.02-1.35 per 10 μg/m ), PM (1.12, 0.92-1.36 per 5 μg/m ), and BC (1.15, 1.00-1.33 per 0.5 10 /m) and liver cancer incidence. Associations with NO and BC persisted in two-pollutant models with PM . Most components of PM were associated with the risk of liver cancer, with the strongest associations for sulfur and vanadium, which were robust to adjustment for PM or NO . Our study suggests that ambient air pollution may increase the risk of liver cancer, even at concentrations below current EU standards. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ijc.33743DOI Listing
July 2021

Hysterectomy, non-malignant gynecological diseases, and the risk of incident hypertension: The E3N prospective cohort.

Maturitas 2021 Aug 12;150:22-29. Epub 2021 Jun 12.

CHU Rennes, Université de Rennes 1-Rennes, France.

Objectives: While it has been reported that women with uterine fibroids or endometriosis are commonly overweight and hypertensive, the association between non-malignant gynecological diseases and the risk of hypertension has been little studied prospectively. The aim of this study was to investigate in a large French cohort of women whether a history of hysterectomy, uterine fibroids, or endometriosis was prospectively related to an increased risk of incident hypertension.

Study Design: We analyzed 50,286 women from the E3N cohort who were free of hypertension at baseline, with a median follow-up of 16.4 years.

Main Outcome Measures: Gynecological diseases were based on self-report. Cox proportional hazards models with age as the timescale were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Covariates included smoking status, body mass index (BMI), physical activity, and hormonal factors.

Results: A total of 12,073 women (24%) developed hypertension during follow-up. Women with a history of hysterectomy had an increased risk of incident hypertension, which persisted after adjustment for potential confounding factors (adjusted HR=1.18, 95% CI 1.12-1.24). Risk was similar in women with hysterectomy with or without oophorectomy. Risk of hypertension was higher in women with a history of endometriosis (HR 1.19, 95%CI 1.11-1.22) or uterine fibroids (HR 1.18, 95%CI 1.13-1.22), irrespective of hysterectomy. Associations were similar after further adjustment for BMI.

Conclusions: Hysterectomy and non-malignant gynecological diseases were associated with an increased risk of hypertension in this large prospective study. Women with these conditions may benefit from blood pressure monitoring. ClinicalTrials.gov identifier: NCT03285230.
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http://dx.doi.org/10.1016/j.maturitas.2021.06.001DOI Listing
August 2021

Plasma concentrations of persistent organic pollutants and pancreatic cancer risk.

Int J Epidemiol 2021 Jul 14. Epub 2021 Jul 14.

Cancer Registry and Histopathology Department, "Civic-M.P. Arezzo" Hospital, ASP Ragusa, Ragusa, Italy.

Background: Findings and limitations of previous studies on persistent organic pollutants (POPs) and pancreatic cancer risk support conducting further research in prospective cohorts.

Methods: We conducted a prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Participants were 513 pancreatic cancer cases and 1020 matched controls. Concentrations of 22 POPs were measured in plasma collected at baseline.

Results: Some associations were observed at higher concentrations of p, p'-DDT, trans-nonachlor, β-hexachlorocyclohexane and the sum of six organochlorine pesticides and of 16 POPs. The odds ratio (OR) for the upper quartile of trans-nonachlor was 1.55 (95% confidence interval 1.06-2.26; P for trend = 0.025). Associations were stronger in the groups predefined as most valid (participants having fasted >6 h, with microscopic diagnostic confirmation, normal weight, and never smokers), and as most relevant (follow-up ≥10 years). Among participants having fasted >6 h, the ORs were relevant for 10 of 11 exposures. Higher ORs were also observed among cases with microscopic confirmation than in cases with a clinical diagnosis, and among normal-weight participants than in the rest of participants. Among participants with a follow-up ≥10 years, estimates were higher than in participants with a shorter follow-up (for trans-nonachlor: OR = 2.14, 1.01 to 4.53, P for trend = 0.035). Overall, trans-nonachlor, three PCBs and the two sums of POPs were the exposures most clearly associated with pancreatic cancer risk.

Conclusions: Individually or in combination, most of the 22 POPs analysed did not or only moderately increased the risk of pancreatic cancer.
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http://dx.doi.org/10.1093/ije/dyab115DOI Listing
July 2021

BMI in the Associations of Plant-Based Diets with Type 2 Diabetes and Hypertension Risks in Women: The E3N Prospective Cohort Study.

J Nutr 2021 Jun 3. Epub 2021 Jun 3.

Paris-Saclay University, UVSQ, University Paris-Sud, Inserm, Gustave Roussy, "Exposome and Heredity" Team, CESP, Villejuif, France.

Background: Few studies have evaluated the quality of plant-based diets in relation to chronic diseases, and the potential role of BMI is not clearly explored.

Objectives: To study the associations between plant-based diet indices and type 2 diabetes (T2D) and hypertension risks, as well as the extent to which the associations were modified and/or mediated by BMI.

Methods: The study included 74,522 women from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale prospective cohort [mean (SD): age, 52.94 (6.7) years; BMI, 22.970 (3.328) kg/m2]. Dietary data were collected at baseline (1993) via an FFQ. Overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) were developed. Multivariable Cox regression models were used to derive HRs and 95% CIs. Effect modification and mediation by BMI were explored.

Results: There were 3292 (4.64%) incident cases of T2D and 12,504 (27.14%) incident cases of hypertension over ∼20 years of follow-up. In the multivariable model further adjusted for BMI, higher adherence to PDI and hPDI was associated with lower T2D and hypertension risks, with an HR per 1-SD increase (95% CI) of 0.88 (0.85, 0.91) and 0.96 (0.94, 0.98) for PDI and 0.88 (0.85, 0.92) and 0.94 (0.92, 0.95) for hPDI, respectively. uPDI was not associated with T2D [0.98 (0.94, 1.01)], whereas a positive association was observed with hypertension: 1.04 (1.02, 1.06). There was interaction between PDI and uPDI, as well as BMI, on T2D (P-interaction < 0.001) but not on hypertension (P-interaction > 0.05). In addition, BMI mediated 26-59% and 0.2-59% of diet-T2D and diet-hypertension associations, respectively.

Conclusions: Differential associations between plant-based diets and T2D and hypertension risks were observed among women in this large prospective study. Only healthier plant foods were associated with lower risks, partly through decreasing BMI. The protocol was registered at clinicaltrials.gov as NCT03285230.
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http://dx.doi.org/10.1093/jn/nxab158DOI Listing
June 2021

Type 2 diabetes and its characteristics are associated with poor oral health: findings from 60,590 senior women from the E3N study.

BMC Oral Health 2021 06 23;21(1):315. Epub 2021 Jun 23.

Center for Research in Epidemiology and Population Health (CESP), Inserm (Institut National de la Santé Et de la Recherche Médicale) U1018, Generations and Health, Gustave Roussy Institute, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, France.

Background: Type 2 diabetes (T2D) has been identified as a risk factor for poor oral health, however, a limited number of oral health and T2D characteristics have been studied so far. We sought to assess T2D status, age at diagnosis, duration since diagnosis and treatment in relation to a variety of oral diseases.

Methods: Cross-sectional data were analyzed from the E3N (Etude Epidémiologique auprès de femmes de l'Education Nationale) cohort study which enrolled 60,590 women. Participants self-reported oral health status, and T2D cases were identified using diabetes-specific questionnaires and drug reimbursement insurance databases. Multivariable-adjusted ORs and 95% CIs were estimated using logistic regression models.

Results: The mean age (SD) of the women was 70 years (7.2), and 4.7% (n = 2857) had T2D. Compared to women without T2D, women with T2D were more likely to report a poor perceived oral health (OR 1.37 [95% CI 1.18, 1.60]), wearing dental prostheses (1.26 [1.14, 1.39]) and having problems of biting and chewing food (1.19 [1.07, 1.33]). In addition, for women with T2D the age at diagnosis (inversely) and the duration (positively) were associated with the likelihood to report poor oral health.

Conclusions: For women with T2D, duration and age at diagnosis are associated with wearing prostheses, problems of biting and chewing, periodontitis and gingivitis.
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http://dx.doi.org/10.1186/s12903-021-01679-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220760PMC
June 2021

Long-term exposure to low-level air pollution and incidence of asthma: the ELAPSE project.

Eur Respir J 2021 06 4;57(6). Epub 2021 Jun 4.

Dept of Environmental Science, Aarhus University, Roskilde, Denmark.

Background: Long-term exposure to ambient air pollution has been linked to childhood-onset asthma, although evidence is still insufficient. Within the multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we examined the associations of long-term exposures to particulate matter with a diameter <2.5 µm (PM), nitrogen dioxide (NO) and black carbon (BC) with asthma incidence in adults.

Methods: We pooled data from three cohorts in Denmark and Sweden with information on asthma hospital diagnoses. The average concentrations of air pollutants in 2010 were modelled by hybrid land-use regression models at participants' baseline residential addresses. Associations of air pollution exposures with asthma incidence were explored with Cox proportional hazard models, adjusting for potential confounders.

Results: Of 98 326 participants, 1965 developed asthma during a mean follow-up of 16.6 years. We observed associations in fully adjusted models with hazard ratios of 1.22 (95% CI 1.04-1.43) per 5 μg·m for PM, 1.17 (95% CI 1.10-1.25) per 10 µg·m for NO and 1.15 (95% CI 1.08-1.23) per 0.5×10m for BC. Hazard ratios were larger in cohort subsets with exposure levels below the European Union and US limit values and possibly World Health Organization guidelines for PM and NO. NO and BC estimates remained unchanged in two-pollutant models with PM, whereas PM estimates were attenuated to unity. The concentration-response curves showed no evidence of a threshold.

Conclusions: Long-term exposure to air pollution, especially from fossil fuel combustion sources such as motorised traffic, was associated with adult-onset asthma, even at levels below the current limit values.
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http://dx.doi.org/10.1183/13993003.03099-2020DOI Listing
June 2021

Thyroid dysfunction and breast cancer risk among women in the UK Biobank cohort.

Cancer Med 2021 Jul 26;10(13):4604-4614. Epub 2021 May 26.

Epidemiology of radiation Group, Center for Research in Epidemiology and Population Health, INSERM U1018, Paris Sud-Paris Saclay University, Villejuif, France.

This study aimed to evaluate the association between thyroid dysfunction and breast cancer risk. We included 239,436 females of the UK Biobank cohort. Information on thyroid dysfunction, personal and family medical history, medications, reproductive factors, lifestyle, and socioeconomic characteristics was retrieved from baseline self-reported data and hospital inpatient databases. Breast cancer diagnoses were identified through population-based registries. We computed Cox models to estimate hazard ratios (HRs) of breast cancer incidence for thyroid dysfunction diagnosis and treatments, and examined potential confounding and effect modification by comorbidities and breast cancer risk factors. In our study, 3,227 (1.3%) and 20,762 (8.7%) women had hyper- and hypothyroidism prior to the baseline. During a median follow-up of 7.1 years, 5,326 (2.2%) women developed breast cancer. Compared to no thyroid dysfunction, there was no association between hypothyroidism and breast cancer risk overall (HR = 0.93, 95% confidence interval (CI): 0.84-1.02, 442 cases), but we found a decreased risk more than 10 years after hypothyroidism diagnosis (HR=0.85, 95%CI 0.74-0.97, 226 cases). There was no association with hyperthyroidism overall (HR=1.08, 95%CI 0.86-1.35, 79 cases) but breast cancer risk was elevated among women with treated hyperthyroidism (HR=1.38, 95%CI: 1.03-1.86, 44 cases) or aged 60 years or more at hyperthyroidism diagnosis (HR=1.74, 95%CI: 1.01-3.00, 113 cases), and 5-10 years after hyperthyroidism diagnosis (HR=1.58, 95%CI: 1.06-2.33, 25 cases). In conclusion, breast cancer risk was reduced long after hypothyroidism diagnosis, but increased among women with treated hyperthyroidism. Future studies are needed to determine whether the higher breast cancer risk observed among treated hyperthyroidism could be explained by hyperthyroidism severity, type of treatment or aetiology.
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http://dx.doi.org/10.1002/cam4.3978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267139PMC
July 2021

The associations of the Palaeolithic diet alone and in combination with lifestyle factors with type 2 diabetes and hypertension risks in women in the E3N prospective cohort.

Eur J Nutr 2021 Apr 28. Epub 2021 Apr 28.

Paris-Saclay University, UVSQ, Univ. Paris-Sud, Inserm U1018, "Exposome, Heredity, Cancer, and Health" Team, CESP, Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, France.

Purpose: Patterns of change from the traditional Palaeolithic lifestyle to the modern lifestyle may partly explain the epidemic proportions of non-communicable diseases (NCDs). We investigated to what extent adherence to the Palaeolithic diet (PD) and the Palaeolithic-like lifestyle was associated with type 2 diabetes (T2D) and hypertension risks.

Methods: A study of 70,991 women from the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort, followed up for nearly 20 years. There were 3292 incident T2D and 12,504 incident hypertension cases that were validated. Dietary data were collected at baseline in 1993 via a food frequency questionnaire. The PD score and the Palaeolithic-like lifestyle score (PD, physical activity, smoking status, and body mass index [BMI]) were derived and considered in quintiles. Multivariable Cox regression models were employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for incident T2D and hypertension.

Results: In the fully adjusted models, a 1-SD increase of the PD score was associated with 4% and 3% lower risks of T2D and hypertension, respectively. Those in the highest versus the lowest quintile of the score had HR (95% CI) of 0.88 (0.79, 0.98) and 0.91 (0.86, 0.96) for T2D and hypertension, respectively (P-trend < 0.0001). Associations were stronger for the Palaeolithic-like lifestyle score; in the fully adjusted model, a 1-SD increase of the score was associated with 19% and 6% lower risks of T2D and hypertension, respectively. Risks lowered successively with each increase in quintile; those in the highest versus the lowest quintile had HR (95% CI) of 0.58 (0.52, 0.65) and 0.85 (0.80, 0.90) for T2D and hypertension, respectively (P-trend < 0.0001).

Conclusions: Our data suggest that adhering to a PD based on fruit, vegetables, lean meats, fish, and nuts, and incorporating a Palaeolithic-like lifestyle could be promising options to prevent T2D and hypertension.
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http://dx.doi.org/10.1007/s00394-021-02565-5DOI Listing
April 2021

Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma.

Sci Rep 2021 Apr 26;11(1):8932. Epub 2021 Apr 26.

Inserm, U900, Institut Curie, PSL University, Mines ParisTech, 75248, Paris, France.

Variants identified in earlier genome-wide association studies (GWAS) on differentiated thyroid carcinoma (DTC) explain about 10% of the overall estimated genetic contribution and could not provide complete insights into biological mechanisms involved in DTC susceptibility. Integrating systems biology information from model organisms, genome-wide expression data from tumor and matched normal tissue and GWAS data could help identifying DTC-associated genes, and pathways or functional networks in which they are involved. We performed data mining of GWAS data of the EPITHYR consortium (1551 cases and 1957 controls) using various pathways and protein-protein interaction (PPI) annotation databases and gene expression data from The Cancer Genome Atlas. We identified eight DTC-associated genes at known loci 2q35 (DIRC3), 8p12 (NRG1), 9q22 (FOXE1, TRMO, HEMGN, ANP32B, NANS) and 14q13 (MBIP). Using the EW_dmGWAS approach we found that gene networks related to glycogenolysis, glycogen metabolism, insulin metabolism and signal transduction pathways associated with muscle contraction were overrepresented with association signals (false discovery rate adjusted p-value < 0.05). Additionally, suggestive association of 21 KEGG and 75 REACTOME pathways with DTC indicate a link between DTC susceptibility and functions related to metabolism of cholesterol, amino sugar and nucleotide sugar metabolism, steroid biosynthesis, and downregulation of ERBB2 signaling pathways. Together, our results provide novel insights into biological mechanisms contributing to DTC risk.
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http://dx.doi.org/10.1038/s41598-021-88253-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076215PMC
April 2021

Association of Migraine With Incident Hypertension After Menopause: A Longitudinal Cohort Study.

Neurology 2021 07 21;97(1):e34-e41. Epub 2021 Apr 21.

From Center for Research in Epidemiology and Population Health (CESP) (C.J.M., D.E.F., A.-L.M., G.S., M.-C.B.-R.), Institut Gustave Roussy, INSERM (Institut National de la Santé et de la Recherche Médicale) U1018; Université Paris-Saclay (C.J.M., D.E.F., A.-L.M., G.S., M.-C.B.-R.), Université Paris-Sud, Villejuif; EA 2694-Santé Publique: Épidémiologie et Qualité des Soins (A.-L.M.), Université de Lille, CHU Lille, France; Deep Digital Phenotyping Research Unit, Department of Population Health (G.F.), Luxembourg Institute of Health, Strassen; Institute of Public Health Charité-Universitätsmedizin Berlin (T.K.), Germany; and Department of Statistics, Computer Science and Applications (DISIA) (G.S.), University of Florence, Italy.

Objective: Migraine has been identified as a potential risk factor for hypertension in prospective studies. In women, migraine prevalence decreases after menopause, but no studies have determined whether migraine is associated with hypertension after menopause. This study sought to determine whether history of migraine was associated with an increased risk of hypertension among menopausal women.

Methods: We assessed associations between migraine and hypertension in a longitudinal cohort study of 56,202 menopausal women participating in the French E3N cohort, with follow-up beginning in 1993. We included women who did not have hypertension or cardiovascular disease at the time of menopause. Migraine was classified as ever or never at each questionnaire cycle. Cox proportional hazards models were used to investigate relations between migraine and hypertension, controlling for potential confounding. A secondary analysis with baseline in 2011 considered aura status, grouping participants reporting migraine as migraine with aura, migraine without aura, or unknown migraine type.

Results: During 826,419 person-years, 12,501 cases of incident hypertension were identified, including 3,100 among women with migraine and 9,401 among women without migraine. Migraine was associated with an increased risk of hypertension in menopausal women (hazard ratio [HR] 1.29 [95% confidence interval 1.24, 1.35]) and was consistent in post hoc sensitivity analyses, such as when controlling for common migraine medications. Associations between migraine and hypertension were similar whether or not women reported aura (HR 1.54 [1.04, 2.30], HR 1.32 [0.87, 2.02], heterogeneity 0.60). Associations were slightly stronger among ever users of menopausal hormone therapy (HR 1.34 [1.27, 1.41]) than among never users (HR 1.19 [1.11, 1.28]).

Conclusions: Migraine was associated with an increased risk of hypertension among menopausal women. In secondary analysis, we did not observe a significant difference between migraine with aura and migraine without aura.
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http://dx.doi.org/10.1212/WNL.0000000000011986DOI Listing
July 2021

Association of Pre-diagnostic Antibody Responses to Escherichia coli and Bacteroides fragilis Toxin Proteins with Colorectal Cancer in a European Cohort.

Gut Microbes 2021 Jan-Dec;13(1):1-14

Department of Medical Biosciences, Pathology, Umeå University, Ireland.

Experimental evidence has implicated genotoxic () and enterotoxigenic (ETBF) in the development of colorectal cancer (CRC). However, evidence from epidemiological studies is sparse. We therefore assessed the association of serological markers of and ETBF exposure with odds of developing CRC in the European Prospective Investigation into Nutrition and Cancer (EPIC) study.Serum samples of incident CRC cases and matched controls (n = 442 pairs) were analyzed for immunoglobulin (Ig) A and G antibody responses to seven proteins and two isoforms of the ETBF toxin via multiplex serology. Multivariable-adjusted conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of sero-positivity to and ETBF with CRC.The IgA-positivity of any of the tested antigens was associated with higher odds of developing CRC (OR: 1.42; 95% CI: 1.05-1.91). Dual-positivity for both IgA and IgG to and ETBF was associated with >1.7-fold higher odds of developing CRC, with a significant association only for IgG (OR: 1.75; 95% CI: 1.04, 2.94). This association was more pronounced when restricted to the proximal colon cancers (OR: 2.62; 95% CI: 1.09, 6.29) compared to those of the distal colon (OR: 1.24; 95% CI: 0.51, 3.00) (= 0.095). Sero-positivity to and ETBF was associated with CRC development, suggesting that co-infection of these bacterial species may contribute to colorectal carcinogenesis. These findings warrant further exploration in larger prospective studies and within different population groups.
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http://dx.doi.org/10.1080/19490976.2021.1903825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078709PMC
April 2021

Fine-mapping of two differentiated thyroid carcinoma susceptibility loci at 2q35 and 8p12 in Europeans, Melanesians and Polynesians.

Oncotarget 2021 Mar 2;12(5):493-506. Epub 2021 Mar 2.

University Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, Exposome and Heredity Team, Villejuif, France.

Differentiated thyroid carcinoma (DTC) incidence is characterized by wide ethnic and geographic variations, with high incidence rates observed in Oceanian populations. Genome-wide association studies (GWAS) identified mainly four DTC susceptibility loci at 9q22.33, 14q13.3, 2q35 and 8p12. Here we performed fine-mapping of the 2q35 and 8p12 loci in the population of the EPITHYR consortium that includes Europeans, Melanesians and Polynesians to identify likely causal variants for DTC risk. We conducted a colocalization analysis using eQTLs data to determine the SNPs with the highest probability of causality. At 2q35, we highlighted rs16857609 located in . This SNP has a high probability of causality in the three populations, and a significant association in Europeans (OR = 1.4, = 1.9 x 10). It is also associated with expression of and of the nearby gene in thyroid tumour cells. At 8p12, we identified rs7844425 which was significantly associated with DTC in Europeans (OR = 1.32, = 7.6 x 10) and rs2439304, which was highlighted by the colocalization analysis but only moderately associated with DTC in our dataset (OR = 1.2, = 0.001). These SNPs are linked to the expression of in thyroid tissue. Hence, our study identified novel variants at 2q35 and 8p12 to be prioritized for further functional studies.
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http://dx.doi.org/10.18632/oncotarget.27888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939525PMC
March 2021

Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study.

Am J Clin Nutr 2021 06;113(6):1490-1502

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Background: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.

Objectives: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR).

Methods: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.

Results: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.

Conclusions: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
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http://dx.doi.org/10.1093/ajcn/nqab003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168352PMC
June 2021

Investigation of circulating metabolites associated with breast cancer risk by untargeted metabolomics: a case-control study nested within the French E3N cohort.

Br J Cancer 2021 May 15;124(10):1734-1743. Epub 2021 Mar 15.

Université Paris-Saclay, UVSQ, Univ. Paris-Sud, Inserm, Gustave Roussy, Exposome and Heredity Team, Centre for Epidemiology and Population Health, Villejuif, France.

Background: Perturbations in circulating metabolites prior to a breast cancer diagnosis are not well characterised. We aimed to gain more detailed knowledge to help understand and prevent the disease.

Methods: Baseline plasma samples from 791 breast cancer cases and 791 matched controls from the E3N (EPIC-France) cohort were profiled by nuclear magnetic resonance (NMR)-based untargeted metabolomics. Partial least-squares discriminant analysis (PLS-DA) models were built from NMR profiles to predict disease outcome, and odds ratios and false discovery rate (FDR)-adjusted CIs were calculated for 43 identified metabolites by conditional logistic regression.

Results: Breast cancer onset was predicted in the premenopausal subgroup with modest accuracy (AUC 0.61, 95% CI: 0.49-0.73), and 10 metabolites associated with risk, particularly histidine (OR = 1.70 per SD increase, FDR-adjusted CI 1.19-2.41), N-acetyl glycoproteins (OR = 1.53, FDR-adjusted CI 1.18-1.97), glycerol (OR = 1.55, FDR-adjusted CI 1.11-2.18) and ethanol (OR = 1.44, FDR-adjusted CI 1.05-1.97). No predictive capacity or significant metabolites were found overall or for postmenopausal women.

Conclusions: Perturbed metabolism compared to controls was observed in premenopausal but not postmenopausal cases. Histidine and NAC have known involvement in inflammatory pathways, and the robust association of ethanol with risk suggests the involvement of alcohol intake.
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http://dx.doi.org/10.1038/s41416-021-01304-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110540PMC
May 2021

Physical activity and stroke among women - A non-linear relationship.

Prev Med 2021 Sep 27;150:106485. Epub 2021 Feb 27.

INSERM (Institut National de la Santé et de la Recherche Médicale) U1018, Center for Research in Epidemiology and Population Health (CESP), Institut Gustave Roussy, Villejuif, France; Université Paris-Saclay, Université Paris-Sud, Villejuif, France. Electronic address:

Studies have identified non-linear inverse relationships between physical activity and the risk of stroke. A U-shaped response has been observed between haemorrhagic stroke and physical activity. The objective of this study was to investigate the associations between physical activities on stroke. We used data from the E3N cohort study, a French prospective study of women initiated in 1990. From the women in the study, we included those without cardiovascular disease or cancer at baseline, resulting in 94,169 women. We assessed total physical activity in 1993, grouped as quartiles. Cox models adjusted for potential confounders were used to assess the relationship with stroke, considering cases until 2008. Splines were used to assess the shape of the response. Similarly, we then considered high and low-intensity physical activity grouped as tertiles. Among the included women, with a mean age of 51.2 ± 6.7 years, 592 cases of stroke were identified over an average follow-up time of 16.2 years. Total physical activity was associated with a lower stroke risk (HR = 0.38 [0.31, 0.49]). An inverse relationship was observed between physical activity and all stroke sub-types. A non-linear (L-shaped) relationship was observed for all-stroke, and ischemic stroke, and a U-shaped response for sub-arachnoid and intracerebral haemorrhage. High-intensity activities were associated with a U-shaped response for haemorrhagic stroke types. Low-intensity activities were associated with a linear response for all stroke types. Our results support other observations that physical activity may reduce stroke risk.
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http://dx.doi.org/10.1016/j.ypmed.2021.106485DOI Listing
September 2021

Genetic architectures of proximal and distal colorectal cancer are partly distinct.

Gut 2021 Jul 25;70(7):1325-1334. Epub 2021 Feb 25.

Cancer Prevention and Control Program, Catalan Institute of Oncology - IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.

Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.

Results: We identified 13 loci that reached genome-wide significance (p<5×10) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.

Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
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http://dx.doi.org/10.1136/gutjnl-2020-321534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223655PMC
July 2021

Household Cleaning and Poor Asthma Control Among Elderly Women.

J Allergy Clin Immunol Pract 2021 06 23;9(6):2358-2365.e4. Epub 2021 Feb 23.

Université Paris-Saclay, UVSQ, Univ. Paris-Sud, Inserm, Équipe d'Épidémiologie respiratoire intégrative, CESP, Villejuif, France.

Background: Asthma control is suboptimal in nearly half of adults with asthma. Household exposure to disinfectants and cleaning products (DCP) has been associated with adverse respiratory effects, but data on their association with asthma control are scant.

Objectives: To investigate the association between household use of DCP and asthma control in a large cohort of French elderly women.

Methods: We used data from a case-control study on asthma (2011-2013) nested in the E3N cohort. Among 3023 women with current asthma, asthma control was defined by the Asthma Control Test (ACT). We used a standardized questionnaire to assess the frequency of cleaning tasks and DCP use. We also identified household cleaning patterns using a clustering approach. Associations between DCP and ACT were adjusted for age, smoking status, body mass index, and education.

Results: Data on ACT and DCP use were available for 2223 women (70 ± 6 years old). Asthma was controlled (ACT = 25), partly controlled (ACT = 20-24), and poorly controlled (ACT ≤ 19) in 29%, 46%, and 25% of the participants, respectively. Weekly use of sprays and chemicals was associated with poorly controlled asthma (odds ratio [95% confidence interval]: 1 spray: 1.31 [0.94-1.84], ≥2 sprays: 1.65 [1.07-2.53], P trend: .01; 1 chemical: 1.24 [0.94-1.64], ≥2 chemicals: 1.47 [1.03-2.09], P trend: .02). Risk for poor asthma control increased with the patterns "very frequent use of products" (1.74 [1.13-2.70]) and "infrequent cleaning tasks and intermediate use of products" (1.62 [1.05-2.51]).

Conclusion: Regular use of DCP may contribute to poor asthma control in elderly women. Limiting their use may help improve asthma management.
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http://dx.doi.org/10.1016/j.jaip.2021.02.022DOI Listing
June 2021

Red Blood Cell Fatty Acids and Risk of Colorectal Cancer in The European Prospective Investigation into Cancer and Nutrition (EPIC).

Cancer Epidemiol Biomarkers Prev 2021 May 22;30(5):874-885. Epub 2021 Feb 22.

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

Background: A growing body of evidence suggests that alterations of dietary fatty acid (FA) profiles are associated with colorectal cancer risk. However, data from large-scale epidemiologic studies using circulating FA measurements to objectively assess individual FA and FA categories are scarce.

Methods: We investigate the association between red blood cell (RBC) membrane FAs and risk of colorectal cancer in a case-control study nested within a large prospective cohort. After a median follow-up of 6.4 years, 1,069 incident colorectal cancer cases were identified and matched to 1,069 controls among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). The FA composition of RBC phospholipids (in mol%) was analyzed by gas chromatography, and their association with risk of colorectal cancer was estimated by multivariable adjusted conditional logistic regression models.

Results: After correction for multiple testing, subjects with higher concentrations of RBC stearic acid were at higher risk for colorectal cancer (OR = 1.23; 95% CI = 1.07-1.42, per 1 mol%). Conversely, colorectal cancer incidence decreased with increasing proportions of RBC n-3 PUFA, particularly eicosapentaenoic acid (0.75; 0.62-0.92, per 1 mol%). The findings for the n-6 PUFA arachidonic acid were inconsistent.

Conclusions: The positive association between prediagnostic RBC stearic acid and colorectal cancer reflects putative differences in FA intake and metabolism between cancer cases and matched controls, which deserve further investigation. The inverse relationship between EPA and colorectal cancer is in line with the repeatedly reported protective effect of fish consumption on colorectal cancer risk.

Impact: These findings add to the evidence on colorectal cancer prevention.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1426DOI Listing
May 2021

Pepper Alkaloids and Processed Meat Intake: Results from a Randomized Trial and the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort.

Mol Nutr Food Res 2021 04 2;65(7):e2001141. Epub 2021 Mar 2.

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

Scope: Processed meat intake has been associated with adverse health outcomes. However, little is known about the type of processed meat more particularly responsible for these effects. This study aims to identify novel biomarkers for processed meat intake.

Methods And Results: In a controlled randomized cross-over dietary intervention study, 12 healthy volunteers consume different processed and non-processed meats for 3 consecutive days each. Metabolomics analyses are applied on post-intervention fasting blood and urine samples to identify discriminating molecular features of processed meat intake. Nine and five pepper alkaloid metabolites, including piperine, are identified as major discriminants of salami intake in urine and plasma, respectively. The associations with processed meat intake are tested for replication in a cross-sectional study (n = 418) embedded within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Three of the serum metabolites including piperine are associated with habitual intake of sausages and to a lesser extent of total processed meat.

Conclusion: Pepper alkaloids are major discriminants of intake for sausages that contain high levels of pepper used as ingredient. Further work is needed to assess if pepper alkaloids in combination with other metabolites may serve as biomarkers of processed meat intake.
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http://dx.doi.org/10.1002/mnfr.202001141DOI Listing
April 2021

Lifetime alcohol intake, drinking patterns over time and risk of stomach cancer: A pooled analysis of data from two prospective cohort studies.

Int J Cancer 2021 Jun 22;148(11):2759-2773. Epub 2021 Feb 22.

Hellenic Health Foundation, Athens, Greece.

Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (P = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences.
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http://dx.doi.org/10.1002/ijc.33504DOI Listing
June 2021

Female hormonal exposures and risk of rheumatoid arthritis in the French E3N-EPIC cohort study.

Rheumatology (Oxford) 2021 Feb 6. Epub 2021 Feb 6.

Rheumatology Department, Assistance Publique-Hôpitaux de Paris (AP-HP), AP-HP. Université Paris-Saclay-Hôpital Bicêtre, France, Paris.

Objective: To assess the relationships between female hormonal exposures and risk of rheumatoid arthritis (RA), in a prospective cohort of French women.

Methods: E3N is an on-going French prospective cohort that included 98 995 women aged 40-65 years in 1990. Every 2-3 years, women completed mailed questionnaires on their lifestyles, reproductive factors, and health conditions. Cox proportional-hazards regression models were used to determine factors associated with risk of incident RA, with age as the time scale, adjusted for known risk factors of RA, and considering endogenous and exogenous hormonal factors. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. Effect modification by smoking history was investigated.

Results: A total of 698 incident cases of RA were ascertained among 78 452 women. In multivariable-adjusted Cox regression models, risk of RA was increased with early age at first pregnancy (<22 vs ≥27 years; HR = 1.34; 95%CI 1.0-1.7) and menopause (≤45 vs ≥53 years; HR = 1.40; 95%CI 1.0-1.9). For early menopause, the association was of similar magnitude in ever and never smokers, although the association was statistically significant only in ever smokers (HR = 1.54; 95%CI 1.0-2.3). We found a decreased risk in nulliparous women never exposed to smoking (HR = 0.44; 95%CI 0.2-0.8). Risk of RA was inversely associated with exposure to progestogen only in perimenopause (>24 vs 0 months; multi-adjusted HR = 0.77; 95%CI 0.6-0.9).

Conclusions: These results suggest an effect of both endogenous and exogenous hormonal exposures on RA risk and phenotype that deserves further investigation.
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http://dx.doi.org/10.1093/rheumatology/keab101DOI Listing
February 2021

Multiethnic genome-wide association study of differentiated thyroid cancer in the EPITHYR consortium.

Int J Cancer 2021 Jun 24;148(12):2935-2946. Epub 2021 Feb 24.

Inserm, U1078, GGB, Université de Bretagne Occidentale, EFS, Brest, France.

Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. DTC is one of the cancers with the highest familial risk suggesting a major role of genetic risk factors, but only few susceptibility loci were identified so far. In order to assess the contribution of known DTC susceptibility loci and to identify new ones, we conducted a multiethnic genome-wide association study (GWAS) in individuals of European ancestry and of Oceanian ancestry from Pacific Islands. Our study included 1554 cases/1973 controls of European ancestry and 301 cases/348 controls of Oceanian ancestry from seven population-based case-control studies participating to the EPITHYR consortium. All participants were genotyped using the OncoArray-500K Beadchip (Illumina). We confirmed the association with the known DTC susceptibility loci at 2q35, 8p12, 9q22.33 and 14q13.3 in the European ancestry population and suggested two novel signals at 1p31.3 and 16q23.2, which were associated with thyroid-stimulating hormone levels in previous GWAS. We additionally replicated an association with 5p15.33 reported previously in Chinese and European populations. Except at 1p31.3, all associations were in the same direction in the population of Oceanian ancestry. We also observed that the frequencies of risk alleles at 2q35, 5p15.33 and 16q23.2 were significantly higher in Oceanians than in Europeans. However, additional GWAS and epidemiological studies in Oceanian populations are needed to fully understand the highest incidence observed in these populations.
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http://dx.doi.org/10.1002/ijc.33488DOI Listing
June 2021

Development and validation of a lifestyle-based model for colorectal cancer risk prediction: the LiFeCRC score.

BMC Med 2021 Jan 4;19(1). Epub 2021 Jan 4.

Public Health Directorate, Asturias, Spain.

Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population.

Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992-2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed.

Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell's C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264-0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084-0.575)).

Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level.
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http://dx.doi.org/10.1186/s12916-020-01826-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780676PMC
January 2021

Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort.

Clin Gastroenterol Hepatol 2020 Dec 29. Epub 2020 Dec 29.

Escuela Andaluza de Salud Pública, Granada, Spain.

Background & Aims: Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer cohort.

Methods: Scores reflecting adherence to the WCRF/AICR recommendations (scale, 1-5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5738 cancer-free European Prospective Investigation into Cancer participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95% CIs were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression.

Results: Higher WCRF/AICR scores were characterized by metabolic signatures of increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly with colorectal cancer risk (fatty acids: OR, 0.51 per unit increase; 95% CI, 0.29-0.90; endogenous metabolites: OR, 0.62 per unit change; 95% CI, 0.50-0.78) than the WCRF/AICR score (OR, 0.93 per unit change; 95% CI, 0.86-1.00) overall. Signature associations were stronger in male compared with female participants.

Conclusions: Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.
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http://dx.doi.org/10.1016/j.cgh.2020.11.045DOI Listing
December 2020

Long-term exposure to low-level air pollution and incidence of chronic obstructive pulmonary disease: The ELAPSE project.

Environ Int 2021 01 1;146:106267. Epub 2020 Dec 1.

Department of Environmental Science, Aarhus University, Roskilde, Denmark; Global Centre for Clean Air Research, University of Surrey, Guildford, United Kingdom.

Background: Air pollution has been suggested as a risk factor for chronic obstructive pulmonary disease (COPD), but evidence is sparse and inconsistent.

Objectives: We examined the association between long-term exposure to low-level air pollution and COPD incidence.

Methods: Within the 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE) study, we pooled data from three cohorts, from Denmark and Sweden, with information on COPD hospital discharge diagnoses. Hybrid land use regression models were used to estimate annual mean concentrations of particulate matter with a diameter < 2.5 µm (PM), nitrogen dioxide (NO), and black carbon (BC) in 2010 at participants' baseline residential addresses, which were analysed in relation to COPD incidence using Cox proportional hazards models.

Results: Of 98,058 participants, 4,928 developed COPD during 16.6 years mean follow-up. The adjusted hazard ratios (HRs) and 95% confidence intervals for associations with COPD incidence were 1.17 (1.06, 1.29) per 5 µg/m for PM, 1.11 (1.06, 1.16) per 10 µg/m for NO, and 1.11 (1.06, 1.15) per 0.5 10m for BC. Associations persisted in subset participants with PM or NO levels below current EU and US limit values and WHO guidelines, with no evidence for a threshold. HRs for NO and BC remained unchanged in two-pollutant models with PM, whereas the HR for PM was attenuated to unity with NO or BC.

Conclusions: Long-term exposure to low-level air pollution is associated with the development of COPD, even below current EU and US limit values and possibly WHO guidelines. Traffic-related pollutants NO and BC may be the most relevant.
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http://dx.doi.org/10.1016/j.envint.2020.106267DOI Listing
January 2021

The impact of lifecourse socio-economic position and individual social mobility on breast cancer risk.

BMC Cancer 2020 Nov 23;20(1):1138. Epub 2020 Nov 23.

UMR LEASP, Université de Toulouse III, UPS, Inserm, Toulouse, France.

Background: Women with an advantaged socioeconomic position (SEP) have a higher risk of developing breast cancer (BC). The reasons for this association do not seem to be limited to reproductive factors and remain to be understood. We aimed to investigate the impact of lifecourse SEP from childhood and social mobility on the risk of BC considering a broad set of potential mediators.

Methods: We used a discovery-replication strategy in two European prospective cohorts, E3N (N = 83,436) and EPIC-Italy (N = 20,530). In E3N, 7877 women were diagnosed with BC during a median 24.4 years of follow-up, while in EPIC-Italy, 893 BC cases were diagnosed within 15.1 years. Hazard ratios (HR) were estimated using Cox proportional hazard models on imputed data.

Results: In E3N, women with higher education had a higher risk of BC (HR [95%CI] = 1.21 [1.12, 1.30]). This association was attenuated by adjusting for reproductive factors, in particular age at first childbirth (HR[95%CI] = 1.13 [1.04, 1.22]). Health behaviours, anthropometric variables, and BC screening had a weaker effect on the association. Women who remained in a stable advantaged SEP had a higher risk of BC (HR [95%CI] = 1.24 [1.07; 1.43]) attenuated after adjustment for potential mediators (HR [95%CI] = 1.13 [0.98; 1.31]). These results were replicated in EPIC-Italy.

Conclusions: These results confirm the important role of reproductive factors in the social gradient in BC risk, which does not appear to be fully explained by the large set of potential mediators, including cancer screening, suggesting that further research is needed to identify additional mechanisms.
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http://dx.doi.org/10.1186/s12885-020-07648-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684912PMC
November 2020

Pigmentary traits, sun exposure, and risk of non-Hodgkin's lymphoma/chronic lymphocytic leukemia: A study within the French E3N prospective cohort.

Cancer Med 2021 01 21;10(1):297-304. Epub 2020 Nov 21.

Hematology-Oncology Department, Centre Hospitalier de Versailles, Le Chesnay, France.

To investigate whether risk factors for keratinocyte carcinomas (KCs), namely pigmentary traits and sun exposure, are associated with risk of non-Hodgkin's lymphomas (NHL) and chronic lymphocytic leukemia (CLL). E3N is a prospective cohort of French women aged 40-65 years at inclusion in 1990. Cancer data were collected at baseline and updated every 2-3 years. Hazard Ratios (HRs) and 95% confidence intervals (CIs) for associations between pigmentary traits and sun exposure, and risk of CLL/NHL were estimated using Cox models. With a median follow-up of 24 years, 622 incident cases of CLL/NHL were ascertained among the 92,097 included women. The presence of nevi was associated with CLL/NHL risk: HR for "many or very many nevi" relative to "no nevi": 1.56 [1.15; 2.11]. Such association with number of nevi appears to be mostly limited to risk of CLL: HR for "many or very many nevi": 3.00 [1.38; 6.52]; versus 1.32 [0.94; 1.84] for NHL. Women whose skin was highly sensitive to sunburn also had a higher risk of CLL: HR = 1.96 [1.21; 3.18], while no increase in risk of NHL was observed. Skin or hair color, number of freckles, and average daily ultraviolet (UV) dose during spring and summer in location of residence at birth or at inclusion (kJ/m ) were not associated with CLL/NHL risk. Some pigmentary traits (presence of nevi and skin sensitivity), but not sun exposure, were associated with CLL/NHL. These observations suggest that CLL may share some constitutional risk factors with keratinocyte cancers.
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http://dx.doi.org/10.1002/cam4.3586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826467PMC
January 2021

Long-term low-level ambient air pollution exposure and risk of lung cancer - A pooled analysis of 7 European cohorts.

Environ Int 2021 01 13;146:106249. Epub 2020 Nov 13.

Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden; Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden. Electronic address:

Background/aim: Ambient air pollution has been associated with lung cancer, but the shape of the exposure-response function - especially at low exposure levels - is not well described. The aim of this study was to address the relationship between long-term low-level air pollution exposure and lung cancer incidence.

Methods: The "Effects of Low-level Air Pollution: a Study in Europe" (ELAPSE) collaboration pools seven cohorts from across Europe. We developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates for nitrogen dioxide (NO), fine particulate matter (PM), black carbon (BC), and ozone (O) to assign exposure to cohort participants' residential addresses in 100 m by 100 m grids. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socio-economic status). We fitted linear models, linear models in subsets, Shape-Constrained Health Impact Functions (SCHIF), and natural cubic spline models to assess the shape of the association between air pollution and lung cancer at concentrations below existing standards and guidelines.

Results: The analyses included 307,550 cohort participants. During a mean follow-up of 18.1 years, 3956 incident lung cancer cases occurred. Median (Q1, Q3) annual (2010) exposure levels of NO, PM, BC and O (warm season) were 24.2 µg/m (19.5, 29.7), 15.4 µg/m (12.8, 17.3), 1.6 10m (1.3, 1.8), and 86.6 µg/m (78.5, 92.9), respectively. We observed a higher risk for lung cancer with higher exposure to PM (HR: 1.13, 95% CI: 1.05, 1.23 per 5 µg/m). This association was robust to adjustment for other pollutants. The SCHIF, spline and subset analyses suggested a linear or supra-linear association with no evidence of a threshold. In subset analyses, risk estimates were clearly elevated for the subset of subjects with exposure below the EU limit value of 25 µg/m. We did not observe associations between NO, BC or O and lung cancer incidence.

Conclusions: Long-term ambient PM exposure is associated with lung cancer incidence even at concentrations below current EU limit values and possibly WHO Air Quality Guidelines.
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http://dx.doi.org/10.1016/j.envint.2020.106249DOI Listing
January 2021

Associations Between Physical Activity and Incident Hypertension Across Strata of Body Mass Index: A Prospective Investigation in a Large Cohort of French Women.

J Am Heart Assoc 2020 12 14;9(23):e015121. Epub 2020 Nov 14.

Institut National de la Santé et de la Recherche Médicale U1018 Center for Research in Epidemiology and Population Health Institut Gustave Roussy Villejuif France.

Background High body mass index (BMI) and low physical activity are associated with increased risk of hypertension. Few studies have assessed their joint impact or the relation of physical activity and hypertension among individuals within a healthy BMI range. The objective of this study was to investigate the associations between physical activity and hypertension across strata of BMI. Methods and Results We used data from the E3N (Etude Epidémiologique de femmes de la Mutuelle Générale de l´Education) cohort, a French prospective study of women aged 40 to 65 years. We included participants who completed a diet history questionnaire and who did not have prevalent hypertension at baseline, resulting in a total of 41 607 women. Questionnaires assessed time spent undertaking various types of physical activity. Hypertension cases were self-reported. Cox models were used to calculate hazard ratios (HRs) for physical activity. Associations were assessed over strata of BMI. Among the 41 607 included women, 10 182 cases of hypertension were identified in an average follow-up time of 14.5 years. Total physical activity was associated with a lower hypertension risk in women within the high-normal BMI range (BMI, 22.5-24.9) (HR , 0.89; 95% CI, 0.79-0.99). An inverse relationship was observed between sports (HR, 0.87; 95% CI, 0.83-0.93), walking (HR, 0.94; 95% CI, 0.90-1.00), and gardening (HR, 0.94; 95% CI, 0.89-0.99). Sports were associated with a reduced risk of hypertension in women with a healthy weight, but evidence was weaker in overweight/obese or underweight women. Conclusions Women with a healthy weight were those who could benefit most from practicing sports, and sports provided the largest risk reduction compared with other types of activity.
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http://dx.doi.org/10.1161/JAHA.119.015121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763781PMC
December 2020

Association between anthropometry and lifestyle factors and risk of B-cell lymphoma: An exposome-wide analysis.

Int J Cancer 2021 May 12;148(9):2115-2128. Epub 2020 Nov 12.

Department of Oncology, Lund University, Lund, Sweden.

To better understand the role of individual and lifestyle factors in human disease, an exposome-wide association study was performed to investigate within a single-study anthropometry measures and lifestyle factors previously associated with B-cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2402 incident BCL cases were diagnosed from 475 426 participants that were followed-up on average 14 years. Standard and penalized Cox regression models as well as principal component analysis (PCA) were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, diet and BCL and/or the subtypes. PCAs confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B-cell lymphoma (DLBCL) and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL.
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http://dx.doi.org/10.1002/ijc.33369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048490PMC
May 2021
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