Polyphenol Intake and Epithelial Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study

We thank Bertrand Hemon for his valuable help with the EPIC database. We also thank the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, and the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands; Public Health Directorate, Asturias, Spain; the Oxford University, the Cambridge University, and the Imperial College of London, the UK, for their contribution and ongoing support to the EPIC Study. The authors also express their gratitude to all participants in the EPIC cohorts for their invaluable contribution to the study. This research was funded by the Women's Health Dexeus Foundation (R.Z.-R.). The coordination of EPIC is financially supported by the International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology-ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). We thank CERCA Program/Generalitat de Catalunya for institutional support. R.Z.-R. would like to thank the "Miguel Servet" program (CPII20/00009) from the Institute of Health Carlos III (Spain) and the European Social Fund (ESF).Despite some epidemiological evidence on the protective effects of polyphenol intake on epithelial ovarian cancer (EOC) risk from case-control studies, the evidence is scarce from prospective studies and non-existent for several polyphenol classes. Therefore, we aimed to investigate the associations between the intake of total, classes and subclasses of polyphenols and EOC risk in a large prospective study. The study was conducted in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which included 309,129 adult women recruited mostly from the general population. Polyphenol intake was assessed through validated country-specific dietary questionnaires and the Phenol-Explorer database. During a mean follow-up of 14 years, 1469 first incident EOC cases (including 806 serous, 129 endometrioid, 102 mucinous, and 67 clear cell tumours) were identified. In multivariable-adjusted Cox regression models, the hazard ratio in the highest quartile of total polyphenol intake compared with the lowest quartile (HRQ4vsQ1) was 1.14 (95% CI 0.94–1.39; p-trend = 0.11). Similarly, the intake of most classes and subclasses of polyphenols were not related to either overall EOC risk or any EOC subtype. A borderline statistically significant positive association was observed between phenolic acid intake (HRQ4vsQ1 = 1.20, 95% CI 1.01–1.43; p-trend = 0.02) and EOC risk, especially for the serous subtype and in women with obesity, although these associations did not exceed the Bonferroni correction threshold. The current results do not support any association between polyphenol intake and EOC in our large European prospective study. Results regarding phenolic acid intake need further investigationJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, UtrechtNational Institute for Public Health and the Environment (RIVM), Bilthoven, the NetherlandsPublic Health Directorate, Asturias, SpainOxford UniversityWorld Health OrganizationNIHR Imperial Biomedical Research Centre (BRC)Danish Cancer SocietyLigue nationale contre le cancerInstitut Gustave RoussyMutuelle Generale de l'Education NationaleInstitut National de la Sante et de la Recherche Medicale (Inserm)Deutsche Krebshilfe Helmholtz Association Federal Ministry of Education & Research (BMBF)Fondazione AIRC per la ricerca sul cancroConsiglio Nazionale delle Ricerche (CNR)Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds Dutch Prevention Funds Netherlands Organization for Scientific Research (NWO) World Cancer Research Fund (WCRF), Statistics NetherlandsHealth Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII)Swedish Cancer Society Swedish Research CouncilEuropean CommissionVasterbotten (Sweden)Cancer Research UK 14136 C8221/A29017UK Research & Innovation (UKRI) Medical Research Council UK (MRC)European Commission 1000143 MR/M012190/1CERCA Program/Generalitat de Catalunya CPII20/00009 Instituto de Salud Carlos IIIEuropean Social Fund (ESF)University of CambridgeImperial College of London, the UKWomen's Health Dexeus Foundatio

Baseline and lifetime alcohol consumption and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC)

Experimental evidence suggests that alcohol induces cutaneous carcinogenesis, yet epidemiological studies on the link between alcohol intake and skin cancer have been inconsistent. The European Prospective Investigation into Cancer and Nutrition (EPIC) is a prospective cohort initiated in 1992 in 10 European countries. Alcohol intake at baseline and average lifetime alcohol intake were assessed using validated country-specific dietary and lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in Cox models. A total of 14 037 skin cancer cases (melanoma: n = 2457; basal-cell carcinoma (BCC): n = 8711; squamous-cell carcinoma (SCC): n = 1928; unknown: n = 941) were identified among 450 112 participants (average follow-up: 15 years). Baseline alcohol intake was positively associated with SCC (>15 vs 0.1-4.9 g/day: HR = 1.44, 95% CI = 1.17-1.77; Ptrend = .001), BCC (HR = 1.12, 95% CI = 1.01-1.23; Ptrend = .04), and melanoma risks in men (HR = 1.17, 95% CI = 0.95-1.44; Ptrend = .17), while associations were more modest in women (SCC: HR = 1.09, 95% CI = 0.90-1.30; Ptrend = .13; BCC: HR = 1.08, 95% CI = 1.00-1.17,Ptrend = .03; melanoma: HR = 0.93, 95% CI = 0.80-1.08, Ptrend = .13). Associations were similar for lifetime alcohol intake, with an attenuated linear trend. Lifetime liquor/spirit intake was positively associated with melanoma (fourth vs first quartile: HR = 1.47, 95% CI = 1.08-1.99; Ptrend = .0009) and BCC risks in men (HR = 1.17, 95% CI = 1.04-1.31;Ptrend = .14). Baseline and lifetime intakes of wine were associated with BCC risk (HR = 1.25 in men; HR = 1.11-1.12; in women). No statistically significant associations were found between beverage types and SCC risk. Intake of beer was not associated with skin cancer risk. Our study suggests positive relationships between alcohol intake and skin cancer risk, which may have important implications for the primary prevention of skin cancer. What's new? Drinking alcohol can make the skin more sensitive to sunlight and vulnerable to skin cancer. Here, the authors conducted a large prospective cohort study to evaluate whether alcohol consumption correlates with skin cancer risk. Among the 450 112 participants, there were 2457 cases of melanoma, 8711 of basal cell carcinoma, and 1928 of squamous cell carcinoma. There was a positive association between alcohol and all three cancer types, stronger in men than in women. The association varied somewhat by beverage type

Circulating insulin-like growth factor I in relation to melanoma risk in the European Prospective Investigation into Cancer and Nutrition

Insulin-like growth factor-I (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case-control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma

Coffee and tea drinking in relation to the risk of differentiated thyroid carcinoma: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

PURPOSE: Coffee and tea constituents have shown several anti-carcinogenic activities in cellular and animal studies, including against thyroid cancer (TC). However, epidemiological evidence is still limited and inconsistent. Therefore, we aimed to investigate this association in a large prospective study. METHODS: The study was conducted in the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort, which included 476,108 adult men and women. Coffee and tea intakes were assessed through validated country-specific dietary questionnaires. RESULTS: During a mean follow-up of 14 years, 748 first incident differentiated TC cases (including 601 papillary and 109 follicular TC) were identified. Coffee consumption (per 100 mL/day) was not associated either with total differentiated TC risk (HRcalibrated 1.00, 95% CI 0.97-1.04) or with the risk of TC subtypes. Tea consumption (per 100 mL/day) was not associated with the risk of total differentiated TC (HRcalibrated 0.98, 95% CI 0.95-1.02) and papillary tumor (HRcalibrated 0.99, 95% CI 0.95-1.03), whereas an inverse association was found with follicular tumor risk (HRcalibrated 0.90, 95% CI 0.81-0.99), but this association was based on a sub-analysis with a small number of cancer cases. CONCLUSIONS: In this large prospective study, coffee and tea consumptions were not associated with TC risk.Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom)

Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe : Results from the EPIC prospective cohort study

Background Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations. Methods and findings This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992-2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus (Q1) = 1.07; 95% CI 1.03-1.10, P-trend <0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P <0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out. Conclusions In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.Peer reviewe

Association between nutritional profiles of foods underlying Nutri-Score front-of-pack labels and mortality: EPIC cohort study in 10 European countries.

OBJECTIVE: To determine if the Food Standards Agency nutrient profiling system (FSAm-NPS), which grades the nutritional quality of food products and is used to derive the Nutri-Score front-of-packet label to guide consumers towards healthier food choices, is associated with mortality. DESIGN: Population based cohort study. SETTING: European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from 23 centres in 10 European countries. PARTICIPANTS: 521 324 adults; at recruitment, country specific and validated dietary questionnaires were used to assess their usual dietary intakes. A FSAm-NPS score was calculated for each food item per 100 g content of energy, sugars, saturated fatty acids, sodium, fibre, and protein, and of fruit, vegetables, legumes, and nuts. The FSAm-NPS dietary index was calculated for each participant as an energy weighted mean of the FSAm-NPS score of all foods consumed. The higher the score the lower the overall nutritional quality of the diet. MAIN OUTCOME MEASURE: Associations between the FSAm-NPS dietary index score and mortality, assessed using multivariable adjusted Cox proportional hazards regression models. RESULTS: After exclusions, 501 594 adults (median follow-up 17.2 years, 8 162 730 person years) were included in the analyses. Those with a higher FSAm-NPS dietary index score (highest versus lowest fifth) showed an increased risk of all cause mortality (n=53 112 events from non-external causes; hazard ratio 1.07, 95% confidence interval 1.03 to 1.10, P<0.001 for trend) and mortality from cancer (1.08, 1.03 to 1.13, P<0.001 for trend) and diseases of the circulatory (1.04, 0.98 to 1.11, P=0.06 for trend), respiratory (1.39, 1.22 to 1.59, P<0.001), and digestive (1.22, 1.02 to 1.45, P=0.03 for trend) systems. The age standardised absolute rates for all cause mortality per 10 000 persons over 10 years were 760 (men=1237; women=563) for those in the highest fifth of the FSAm-NPS dietary index score and 661 (men=1008; women=518) for those in the lowest fifth. CONCLUSIONS: In this large multinational European cohort, consuming foods with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher mortality for all causes and for cancer and diseases of the circulatory, respiratory, and digestive systems, supporting the relevance of FSAm-NPS to characterise healthier food choices in the context of public health policies (eg, the Nutri-Score) for European populations. This is important considering ongoing discussions about the potential implementation of a unique nutrition labelling system at the European Union level

Dietary index based on the Food Standards Agency nutrient profiling system and risk of Crohn's disease and ulcerative colitis

Background: Nutri-score is now widely available in food packages in Europe. Aim: To study the overall nutritional quality of the diet in relation to risks of Crohn's disease (CD) and ulcerative colitis (UC), in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: We collected dietary data at baseline from validated food frequency questionnaires. We used a dietary index based on the UK Food Standards Agency modified nutrient profiling system (FSAm-NPS-DI) underlying the Nutri-Score label, to measure the nutritional quality of the diet. We estimated the association between FSAm-NPS-DI score, and CD and UC risks using Cox models stratified by centre, sex and age; and adjusted for smoking status, BMI, physical activity, energy intake, educational level and alcohol intake. Results: We included 394,255 participants (68.1% women; mean age at recruitment 52.1 years). After a mean follow-up of 13.6 years, there were 184 incident cases of CD and 459 incident cases of UC. Risk of CD was higher in those with a lower nutritional quality, that is higher FSAm-NPS-DI Score (fourth vs. first quartile: aHR: 2.04, 95% CI: 1.24–3.36; p-trend: <0.01). Among items of the FSAm-NPS-DI Score, low intakes of dietary fibre and fruits/vegetables/legumes/nuts were associated with higher risk of CD. Nutritional quality was not associated with risk of UC (fourth vs. first quartile of the FSAm-NPS-DI Score: aHR: 0.91, 95% CI: 0.69–1.21; p-trend: 0.76). Conclusions: A diet with low nutritional quality as measured by the FSAm-NPS-DI Score is associated with a higher risk of CD but not UC

Associations between Nutritional Factors and Skin Cancer Risk in the E3N and EPIC Cohorts

Titre : Etude des associations entre facteurs nutritionnels et risque de cancers cutanés dans les cohortes E3N et EPICLes cancers cutanés sont les néoplasmes les plus fréquents chez les populations de type Caucasien et leur incidence est en constante augmentation. L'exposition aux rayonnements ultraviolets (UV) est le seul facteur environnemental reconnu comme cause avérée de cancer de la peau et actuellement le seul pour lequel une prévention est possible. Cependant, il apparait de plus en plus probable que certains facteurs nutritionnels, notamment les antioxydants, pourraient empêcher les effets néfastes de l'exposition aux UV et ainsi potentiellement représenter des agents de chimio-prévention des cancers cutanés. Il a également été suggéré que certains groupes d'aliments, tels que les agrumes, les compléments alimentaires, les acides gras, la vitamine D et l'alcool pouvaient être associés à un risque accru de cancers cutanés. Cependant, les études menées jusqu'à présent n'ont pas permis d'émettre de conclusion claire : peu d'études prospectives avec un échantillon suffisamment important et disposant de données sur l'exposition solaire sont disponibles. Il est donc nécessaire de faire progresser nos connaissances dans ce domaine afin de mieux cibler les campagnes de prévention des cancers cutanés.L’objectif principal de cette thèse était d’explorer les relations entre les facteurs nutritionnels et le risque de cancers cutanés. Les données utilisées dans ce projet incluent les données de la cohorte E3N, incluant près de 100 000 femmes françaises suivies depuis 1990, les données de la cohorte EPIC, incluant près de 520 000 participants issus de 10 pays européens, et les données du PMP, une étude prospective incluant 700 patients australiens atteints de mélanome suivis depuis 2014. De plus, les données de la littérature sur les liens entre vitamine D et mélanome ont été résumées et poolées dans une revue systématique et une méta-analyse.Nos résultats suggèrent que l’adhérence au régime méditerranéen est associée à risque plus faible de cancers cutanés, plus particulièrement de mélanome et de carcinome baso-cellulaire ; en revanche la prise de compléments alimentaires en bêta-carotène, vitamine A ou E était associée à un risque accru de carcinomes cutanés. De plus, nous avons observé que les consommations d’agrumes ou d’alcool étaient associées à un risque plus élevé de cancers cutanés. Par ailleurs, nos résultats suggèrent qu’une forte consommation d’un régime « riche en viande, poisson et graisses » est associée à l’épaisseur du mélanome. Enfin, les résultats de notre méta-analyse suggèrent que les taux circulants élevés de vitamine D sont associés à un risque accru de mélanome et de carcinomes cutanés.Les travaux de cette thèse ont mis en lumière des relations complexes entre les facteurs nutritionnels et le risque de cancers cutanés. Par ailleurs, ils soulèvent plusieurs questions qu’il serait envisageable d’approfondir dans d’autres études. Si ces résultats sont répliqués, ils pourraient, à terme, avoir un impact sur les stratégies de prévention des cancers cutanés.Mots-clés : cancers cutanés ; régime méditerranéen ; compléments en antioxydants ; agrumes ; alcool ; profils alimentaires ; vitamine D ; cohorte prospective ; méta-analyseTitle: Associations between nutritional factors and skin cancer risk in the E3N and EPIC cohortsSkin cancers are the most frequent neoplasms in Caucasian populations and their incidence has been constantly rising. Ultraviolet (UV) radiation exposure is the only environmental risk factor recognized as a cause of skin cancer and the only factor for which prevention is possible. However, it appears increasingly likely that several nutritional factors, particularly antioxidants, could counteract the negative effects of UV exposure and thus potentially represent chemo-preventive agents for skin cancer. It has also been suggested that several food groups, such as citrus, dietary supplements, vitamin D, fatty acids, and alcohol, could be associated with skin cancer risk. However, investigations to date did not allow to draw clear conclusions; few prospective data are indeed available within a sufficiently large sample and available sun exposure data. It is thus crucial to advance our knowledge in this field in order to target skin cancer prevention campaigns more precisely.The objective of this doctoral project was to study the relationships between nutritional factors and skin cancer risk. To achieve our objective, we used data from E3N, a prospective cohort of ~ 100,000 French women followed since 1990, data from EPIC cohort, a prospective cohort involving ~520,000 participants who have been followed-up in 23 centers from 10 European countries, and data from PMP, a prospective study of ~700 melanoma patients diagnosed in Queensland between 2010 and 2014. Additionally, data from the literature were summarized and pooled in a systematic review and meta-analysis.Our results suggest that adherence to the Mediterranean diet is associated with a lower skin cancer risk in women, particularly melanoma and basal-cell carcinoma. Intake of supplements in beta-carotene, vitamin A or E was associated with an increased keratinocyte cancer risk in women. In addition, we found positive linear relationships between citrus intake and skin cancer risk, which were mostly driven by associations with keratinocyte cancers, and between alcohol consumption and overall skin cancer risk. However, our results also suggest that people with high meat, fish, and fat intakes, who thus consumed relatively high levels of omega-3 and high omega-6 fatty acid intakes, are more likely to be diagnosed with thick than thin melanomas. In the meta-analysis, we found positive associations between serum 25(OH)D levels and melanoma and keratinocyte cancer risk.This project highlighted complex relationships between nutritional factors and the risk of skin cancers. It also raised several questions that could be considered for further study. If replicated and confirmed in future research, these findings may ultimately have important implications in skin cancer prevention.Keyword: skin cancer ; Mediterranean diet ; antioxidant supplements ; citrus ; alcohol ; dietary pattern; vitamin D; prospective cohort; meta-analysi

Etude des associations entre facteurs nutritionnels et risque de cancers cutanés dans les cohortes E3N et EPIC

Title: Associations between nutritional factors and skin cancer risk in the E3N and EPIC cohortsSkin cancers are the most frequent neoplasms in Caucasian populations and their incidence has been constantly rising. Ultraviolet (UV) radiation exposure is the only environmental risk factor recognized as a cause of skin cancer and the only factor for which prevention is possible. However, it appears increasingly likely that several nutritional factors, particularly antioxidants, could counteract the negative effects of UV exposure and thus potentially represent chemo-preventive agents for skin cancer. It has also been suggested that several food groups, such as citrus, dietary supplements, vitamin D, fatty acids, and alcohol, could be associated with skin cancer risk. However, investigations to date did not allow to draw clear conclusions; few prospective data are indeed available within a sufficiently large sample and available sun exposure data. It is thus crucial to advance our knowledge in this field in order to target skin cancer prevention campaigns more precisely.The objective of this doctoral project was to study the relationships between nutritional factors and skin cancer risk. To achieve our objective, we used data from E3N, a prospective cohort of ~ 100,000 French women followed since 1990, data from EPIC cohort, a prospective cohort involving ~520,000 participants who have been followed-up in 23 centers from 10 European countries, and data from PMP, a prospective study of ~700 melanoma patients diagnosed in Queensland between 2010 and 2014. Additionally, data from the literature were summarized and pooled in a systematic review and meta-analysis.Our results suggest that adherence to the Mediterranean diet is associated with a lower skin cancer risk in women, particularly melanoma and basal-cell carcinoma. Intake of supplements in beta-carotene, vitamin A or E was associated with an increased keratinocyte cancer risk in women. In addition, we found positive linear relationships between citrus intake and skin cancer risk, which were mostly driven by associations with keratinocyte cancers, and between alcohol consumption and overall skin cancer risk. However, our results also suggest that people with high meat, fish, and fat intakes, who thus consumed relatively high levels of omega-3 and high omega-6 fatty acid intakes, are more likely to be diagnosed with thick than thin melanomas. In the meta-analysis, we found positive associations between serum 25(OH)D levels and melanoma and keratinocyte cancer risk.This project highlighted complex relationships between nutritional factors and the risk of skin cancers. It also raised several questions that could be considered for further study. If replicated and confirmed in future research, these findings may ultimately have important implications in skin cancer prevention.Keyword: skin cancer ; Mediterranean diet ; antioxidant supplements ; citrus ; alcohol ; dietary pattern; vitamin D; prospective cohort; meta-analysisTitre : Etude des associations entre facteurs nutritionnels et risque de cancers cutanés dans les cohortes E3N et EPICLes cancers cutanés sont les néoplasmes les plus fréquents chez les populations de type Caucasien et leur incidence est en constante augmentation. L'exposition aux rayonnements ultraviolets (UV) est le seul facteur environnemental reconnu comme cause avérée de cancer de la peau et actuellement le seul pour lequel une prévention est possible. Cependant, il apparait de plus en plus probable que certains facteurs nutritionnels, notamment les antioxydants, pourraient empêcher les effets néfastes de l'exposition aux UV et ainsi potentiellement représenter des agents de chimio-prévention des cancers cutanés. Il a également été suggéré que certains groupes d'aliments, tels que les agrumes, les compléments alimentaires, les acides gras, la vitamine D et l'alcool pouvaient être associés à un risque accru de cancers cutanés. Cependant, les études menées jusqu'à présent n'ont pas permis d'émettre de conclusion claire : peu d'études prospectives avec un échantillon suffisamment important et disposant de données sur l'exposition solaire sont disponibles. Il est donc nécessaire de faire progresser nos connaissances dans ce domaine afin de mieux cibler les campagnes de prévention des cancers cutanés.L’objectif principal de cette thèse était d’explorer les relations entre les facteurs nutritionnels et le risque de cancers cutanés. Les données utilisées dans ce projet incluent les données de la cohorte E3N, incluant près de 100 000 femmes françaises suivies depuis 1990, les données de la cohorte EPIC, incluant près de 520 000 participants issus de 10 pays européens, et les données du PMP, une étude prospective incluant 700 patients australiens atteints de mélanome suivis depuis 2014. De plus, les données de la littérature sur les liens entre vitamine D et mélanome ont été résumées et poolées dans une revue systématique et une méta-analyse.Nos résultats suggèrent que l’adhérence au régime méditerranéen est associée à risque plus faible de cancers cutanés, plus particulièrement de mélanome et de carcinome baso-cellulaire ; en revanche la prise de compléments alimentaires en bêta-carotène, vitamine A ou E était associée à un risque accru de carcinomes cutanés. De plus, nous avons observé que les consommations d’agrumes ou d’alcool étaient associées à un risque plus élevé de cancers cutanés. Par ailleurs, nos résultats suggèrent qu’une forte consommation d’un régime « riche en viande, poisson et graisses » est associée à l’épaisseur du mélanome. Enfin, les résultats de notre méta-analyse suggèrent que les taux circulants élevés de vitamine D sont associés à un risque accru de mélanome et de carcinomes cutanés.Les travaux de cette thèse ont mis en lumière des relations complexes entre les facteurs nutritionnels et le risque de cancers cutanés. Par ailleurs, ils soulèvent plusieurs questions qu’il serait envisageable d’approfondir dans d’autres études. Si ces résultats sont répliqués, ils pourraient, à terme, avoir un impact sur les stratégies de prévention des cancers cutanés.Mots-clés : cancers cutanés ; régime méditerranéen ; compléments en antioxydants ; agrumes ; alcool ; profils alimentaires ; vitamine D ; cohorte prospective ; méta-analys

25-Hydroxyvitamin D status, vitamin D intake, and skin cancer risk: a systematic review and dose-response meta-analysis of prospective studies

International audienceSun exposure is a major environmental risk factor for skin cancers and is also an important source of vitamin D. However, while experimental evidence suggests that vitamin D may have a protective effect on skin cancer risk, epidemiologic studies investigating the influence of 25-hydroxyvitamin D (25(OH)D) level and/or vitamin D intake on skin cancer risk are conflicting. A systematic review and dose-response meta-analyses of prospective studies was conducted to clarify these associations. Relevant studies were identified by searching the PubMed database up to 30th August 2019. Random effects dose-response meta-analyses were used to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs). Overall, thirteen prospective studies were included. Circulating level of 25(OH)D was associated with higher risks of melanoma (SRR (95% CI) per 30 nmol = 1.42 (1.17-1.72)) and keratinocyte cancer (KC) (SRR (95% CI) per 30 nmol/L = 1.30 (1.13-1.49)). The SRR (95% CI) per 30 nmol/L increase in 25(OH) D level was 1.41 (1.19-1.67), and 1.57 (0.64-3.86), for basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), respectively. However, while we found that vitamin D intake (from diet, supplemental and total) was not associated with risks of melanoma and SCC, vitamin D intake was associated with slightly increased BCC risk, albeit with no heterogeneity across skin cancer type. This meta-analysis suggests positive associations between circulating 25(OH)D level and risk of melanoma and KC, however, this finding is most likely confounded by sun exposure. We found no associations between vitamin D intake skin cancers, except positive associations with BCC risk