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Experimental studies suggested that antioxidants could protect against skin carcinomas. However, epidemiological studies on antioxidant supplement use in relation to basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) risks yielded inconsistent findings, and few prospective studies have been conducted to date. We aimed to investigate the associations between antioxidant supplement intake and keratinocyte cancer (KC) risk.E3N is an ongoing prospective cohort initiated in 1990 and involving 98,995 French women aged 40-65 years at recruitment. Intakes of dietary antioxidants were estimated via a validated dietary questionnaire in 1993 and self-reported antioxidant supplement use was collected in 1995. We used Cox models to compute hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age and skin cancer risk factors.Over 1995-2014, 2426 BCC and 451 SCC cases were diagnosed among 63,063 women. We found positive relationships between vitamin A supplement use and KC risk (HR = 1.37, 95% CI 1.15-1.62), particularly with BCC (HR = 1.40, 95% CI 1.17-1.69); and between vitamin E supplement use and risks of both BCC (HR = 1.21, 95% CI 1.03-1.52) and SCC (HR = 1.43, 95% CI 1.03-1.99). Intake of beta-carotene supplements was associated with an increased SCC risk (HR = 1.59, 95% CI 1.00-2.54). Vitamin C supplement use was not associated with KC risk. We found similar results when considering total antioxidant intake.Intakes of vitamin A or E supplements were associated with an increased KC risk in women. Further studies with information on doses and duration of supplement use and the ability to examine their underlying mechanisms are needed.

We investigated the influence of premenopausal use of progestogens on melanoma using data from E3N (Etude Epidémiologique Auprès de Femmes de l’Education Nationale), a prospective cohort of 98,995 French women, aged 40–65 years at inclusion. We used Cox models to adjust for age and melanoma risk factors. Over 1992–2008, 540 melanoma cases were ascertained among 79,558 women. We found a modest association between self-reported progestogen use and melanoma risk (hazard ratio (HR) = 1.23, 95% confidence interval (CI) = 1.02, 1.47), which was reduced after adjustment for melanoma risk factors (HR = 1.15, 95% CI: 0.95, 1.39). There was no heterogeneity across types of progestogens (P = 0.22), and use of multiple progestogens was positively associated with melanoma risk (HR = 1.33, 95% CI: 1.04, 1.70). Among users, we found no relationship with duration of progestogen use, age at start and last use, and time since first and last use. Although our results did not show evidence of a confounding effect of sun exposure, progestogen users had lower levels of residential sun exposure and were more likely to report sunscreen use, suggesting specific sun exposure profiles in users. Our findings do not support a strong influence of progestogens on melanoma risk. Further research is needed to confirm these results.

This is the peer reviewed version of the following article: Cervenka, I., Al Rahmoun, M., Mahamat-Saleh, Y., Fournier, A., Boutron-Ruault, M.-C., Severi, G. ... Kvaskoff, M. (2019). Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition. International Journal of Cancer, which has been published in final form at https://doi.org/10.1002/ijc.32674. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country‐specific self‐administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline‐significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.

Background The Mediterranean diet (MD) has been reported to be associated with lower cancer risk. However, while previous studies explored major single components of the MD, only 1 previous study has investigated adherence to the MD in relation to melanoma risk. Objective The aim of this study was to explore the relations between adherence to the MD and the risk of skin cancer, including melanomas, basal cell carcinomas (BCCs), and squamous cell carcinomas (SCCs). Design Etude Epidemiologique aupres de femmes de la Mutuelle Generale de l'Education Nationale (E3N) is a prospective cohort of 98,995 French women aged 40-65 y in 1990. Dietary data were collected via a validated food questionnaire in 1993. Adherence to the MD was assessed using a 9-unit dietary score that incorporates intakes of fruit, vegetables, legumes, cereal products, olive oil, fish, dairy products, meat products, and alcohol. We used Cox proportional hazards regression models to compute HRs and 95% CIs adjusted for age and main known skin cancer risk factors. Results From 1993 to 2008, a total of 2003 skin cancer cases were ascertained among 67,332 women, including 404 melanomas, 1367 BCCs, and 232 SCCs. Score of adherence to the MD was associated with lower risk of skin cancer (HR: 0.83; 95% CI: 0.73, 0.93 for high compared with low score, Ptrend = 0.001). MD score was also inversely and linearly associated with risks of melanoma (HR: 0.72; 95% CI: 0.54, 0.96; Ptrend = 0.02) and BCC (HR: 0.77; 95% CI: 0.66, 0.90; Ptrend = 0.0006) but not SCC (HR: 1.08; 95% CI: 0.75, 1.55; Ptrend = 0.68), although with no heterogeneity across skin cancer types (Pheterogeneity = 0.23). Conclusion These findings suggest that adherence to the MD is associated with a lower skin cancer risk in women, particularly melanoma and BCC. If confirmed in future research, these findings may have important implications in skin cancer prevention.

Cutaneous melanoma has been suspected to be influenced by female hormones. Several studies reported a positive association between menopausal hormone therapy (MHT) use and melanoma risk; however, previous findings were conflicting. We sought to explore the associations between MHT use and melanoma risk in a prospective cohort of women in France, where a particularly wide variety of MHT formulations are available. E3N is a prospective cohort of 98,995 French women aged 40-65 years in 1990. MHT use was assessed through biennial self-administered questionnaires. We used Cox proportional hazards regression models adjusted for age and skin cancer risk factors. Over 1990-2008, 444 melanoma cases were ascertained among 75,523 postmenopausal women. Ever use of MHT was associated with a higher melanoma risk (hazard ratio (HR) = 1.35, 95% confidence intervals (CI) = 1.07-1.71). The association was strongest among past users (HR = 1.55, CI = 1.17-2.07, homogeneity for past vs. recent use: p = 0.11), and users of MHT containing norpregnane derivatives (HR = 1.59, CI = 1.11-2.27), although with no heterogeneity across types of MHT (p = 0.13). Among MHT users, the association was similar across durations of use. However, a higher risk was observed when treatment onset occurred shortly after menopause (

International audience; Epidemiological studies on statin use in relation to skin cancer risk are scarce and yielded conflicting results. We explored this association in Etude Epidémiologique auprès de femmes de l'Education Nationale, a prospective cohort of French women born in 1925–1950. Health and lifestyle data were self-reported biennially and matched with drug reimbursement data, allowing the identification of participants’ statin use since 2004. Multivariable cause-specific hazards regression models adjusted for skin cancer risk factors estimated hazard ratios with 95% confidence intervals. Over 2004–2014, 455 cutaneous melanoma, 1,741 basal cell carcinoma, and 268 squamous cell carcinoma cases were ascertained among 62,473 women. Compared with never use, there were no associations between ever use of statins and melanoma (hazard ratio = 1.16, 95% confidence interval = 0.94–1.44) or squamous cell carcinoma (hazard ratio = 0.89, 95% confidence interval = 0.66–1.19) risks and a decrease in basal cell carcinoma risk with ever use of statins (hazard ratio = 0.89, 95% confidence interval = 0.79–0.996). We found no trend of increasing or decreasing risks with dose, duration of use, time since first use, or age at first use and no statistically significant effect modification by pigmentary traits or residential UVR exposure. Because of the limited number of studies evaluating the associations between the use of statins and the risks of melanoma, basal cell carcinoma, and squamous cell carcinoma, these findings would deserve further investigation in other settings.

OBJECTIVES: Experimental studies suggested that antioxidants could protect against skin carcinomas. However, epidemiological studies on antioxidant supplement use in relation to basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) risks yielded inconsistent findings, and few prospective studies have been conducted to date. We aimed to investigate intake of antioxidants supplements and risk of keratinocytes cancers (KCs). METHODS: E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) is a prospective cohort of 98,995 French women aged 40–65 years in 1990. Intakes of antioxidants from diet were estimated via a validated food questionnaire in 1993, and antioxidant supplements use through questionnaires in 1995. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age and main known skin cancer risk factors. RESULTS: Over 1995–2014, 2425 BCC and 451 SCC cases were diagnosed among 63,063 women. We found positive relationships between vitamin A supplement use and KCs risk (HR = 1.37, 95% CI = 1.15–1.62), particularly with BCC (HR = 1.40, 95% CI = 1.17–1.69); and between vitamin E supplement use and risk of both BCC (HR = 1.21, 95% CI = 1.03–1.52) and SCC (HR = 1.43, 95% CI = 1.03–1.99). However, while intake of beta-carotene supplement was associated with increased SCC risk (HR = 1.59, 95% CI = 1.00–2.54), there was not associated with BCC risk, although with no heterogeneity across KC types (P(heterogeneity )= 0.21). Vitamin C supplement was also not associated with KCs. CONCLUSIONS: These findings suggest that intake of vitamin A or E supplement was associated with an increased KCs risk in women. Further studies with information on doses and duration of supplements and the ability to examine their underlying mechanisms are needed. FUNDING SOURCES: This work was supported by the Mutuelle Générale de l'Education Nationale (MGEN); the Gustave Roussy Institute; and the French League against Cancer (LNCC). Yahya Mahamat-Saleh was supported by research scholarships from the Paris Ile-de-France region and the EHESP (French School of Public Health).

Citrus intake has been suggested to increase the risk of skin cancer. Although this relation is highly plausible biologically, epidemiologic evidence is lacking. We aimed to examine the potential association between citrus intake and skin cancer risk. EPIC is an ongoing multi-center prospective cohort initiated in 1992 and involving ~ 520,000 participants who have been followed-up in 23 centers from 10 European countries. Dietary data were collected at baseline using validated country-specific dietary questionnaires. We used Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (CI). During a mean follow-up of 13.7 years, 8448 skin cancer cases were identified among 270,112 participants. We observed a positive linear dose–response relationship between total citrus intake and skin cancer risk (HR = 1.10, 95% CI 1.03–1.18 in the highest vs. lowest quartile; Ptrend = 0.001), particularly with basal cell carcinoma (BCC) (HR = 1.11, 95% CI 1.02–1.20, Ptrend = 0.007) and squamous cell carcinoma (SCC) (HR = 1.23, 95% CI 1.04–1.47, Ptrend = 0.01). Citrus fruit intake was positively associated with skin cancer risk (HR = 1.08, 95% CI 1.01–1.16, Ptrend = 0.01), particularly with melanoma (HR = 1.23, 95% CI 1.02–1.48; Ptrend = 0.01), although with no heterogeneity across skin cancer types (Phomogeneity = 0.21). Citrus juice was positively associated with skin cancer risk (Ptrend = 0.004), particularly with BCC (Ptrend = 0.008) and SCC (Ptrend = 0.004), but not with melanoma (Phomogeneity = 0.02). Our study suggests moderate positive linear dose–response relationships between citrus intake and skin cancer risk. Studies with available biomarker data and the ability to examine sun exposure behaviors are warranted to clarify these associations and examine the phototoxicity mechanisms of furocoumarin-rich foods.

Background: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk. Methods: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non–muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models. Results: During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with urothelial carcinoma risk (HR≥5vs1 = 0.48; 0.25–0.90; Ptrend in parous women = 0.010) and MHT use (compared with nonuse) was positively associated with urothelial carcinoma risk (HR = 1.27; 1.03–1.57), but no dose response by years of MHT use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analyses in never smokers showed similar HR patterns for the number of FTP, while no association between MHT use and urothelial carcinoma risk was observed. Association between MHT use and urothelial carcinoma risk remained significant only in current smokers. No heterogeneity of the risk estimations in the final model was observed by tumor aggressiveness or by tumor grade. A positive association between MTH use and non–muscle-invasive urothelial carcinoma risk was observed. Conclusions: Our results support that increasing the number of FTP may reduce urothelial carcinoma risk. Impact: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells.

Cutaneous melanoma has been suspected to be influenced by female hormones. Several studies reported a positive association between oral contraceptive (OC) use and melanoma risk. However, findings were conflicting and data from large prospective studies are lacking. E3N is a prospective cohort of 98,995 French women aged 40-65 years at inclusion in 1990. Exposure to lifetime OC use was assessed in 1992 and through biennial questionnaire updates. To assess the association between OC use and melanoma risk, we used Cox models adjusted for age, pigmentary traits, residential ultraviolet (UV) exposure in county of birth and at inclusion and family history of skin cancer. Over 1992-2008, 539 melanoma cases were ascertained among 79,365 women. In age-adjusted models, we found a modest positive association between ever use of OCs and melanoma risk (hazard ratio (HR) = 1.18, 95% confidence intervals (CIs) = 0.98-1.42), which was reduced after adjustment (HR = 1.14, 95% CI = 0.95-1.38). The association was stronger in long-term users (duration ≥10 years: HR = 1.33, 95% CI = 1.00-1.75) and in women who used high-estrogen OCs (HR = 1.27, 95% CI = 1.04-1.56). Among users, there was an inverse association with age at first use (ptrend < 0.01), but no evidence of an association with age at last use or time since last use. OC use was positively associated with tanning bed use (OR = 1.14, CI = 1.01-1.29), sunburns (ptrend = 0.5) and sunscreen use (OR = 1.13, CI = 1.00-1.28) since age 25. Overall, our findings do not support a strong association between OC use and melanoma risk and suggest intentional UV exposure in OC users, which supports a potential confusion by UV exposure in this relationship.

Endometriosis has been associated with an increased risk of skin melanoma. However, associations with other skin cancer types and how they compare with melanoma are unclear. Our objective was to prospectively investigate the relationships between endometriosis and risk of non-melanoma and melanoma skin cancers. E3N is a prospective cohort of 98,995 French women aged 40–65 years in 1990. Data on surgically confirmed endometriosis and skin cancer diagnoses were collected every 2–3 years through self-report, with skin cancer cases confirmed through pathology reports. Hazard Ratios (HR) and 95% confidence intervals (CIs) were calculated using Cox regression models. Between 1990 and 2008, 535 melanoma, 247 squamous-cell carcinoma (SCC), and 1,712 basal-cell carcinoma (BCC) cases were ascertained. Endometriosis was associated with an increased overall risk of skin cancer (HR 1.28, 95% CI 1.05–1.55). When considering skin cancer type, endometriosis was associated with melanoma risk (HR 1.64, 95% CI 1.15–2.35), but not with SCC (HR 1.21, 95% CI 0.62–2.36) or BCC (HR 1.16, 95% CI 0.91–1.48) (non-melanoma skin cancers combined: HR 1.17, 95% CI 0.93–1.46), although no heterogeneity was detected across skin cancer types (Phomogeneity = 0.13). These data support an association between a personal history of endometriosis and the risk of skin cancer and suggest that the association is strongest for melanoma.

In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a multicentre prospective study that enrolled over 500,000 participants aged 25–70 years from ten European countries in 1992–2000. Information on coffee and tea drinking was collected at baseline using validated country-specific dietary questionnaires. We used adjusted Cox proportional hazards regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between coffee and tea consumption and melanoma risk. Overall, 2,712 melanoma cases were identified during a median follow-up of 14.9 years among 476,160 study participants. Consumption of caffeinated coffee was inversely associated with melanoma risk among men (HR for highest quartile of consumption vs. non-consumers 0.31, 95% CI 0.14–0.69) but not among women (HR 0.96, 95% CI 0.62–1.47). There were no statistically significant associations between consumption of decaffeinated coffee or tea and the risk of melanoma among both men and women. The consumption of caffeinated coffee was inversely associated with melanoma risk among men in this large cohort study. Further investigations are warranted to confirm our findings and clarify the possible role of caffeine and other coffee compounds in reducing the risk of melanoma.

Cutaneous melanoma has been suspected to be influenced by female sex hormones. A review of the literature in 2018 indicated that fertility drug (FD) use was associated with increased melanoma risk among parous women only. However, most studies so far were based on a retrospective design and the current evidence is unclear. We sought to prospectively investigate the associations between FD use and melanoma risk in women. E3N is a prospective cohort of 98 995 French women aged 40-65 years at inclusion in 1990. Information on use of FDs, including duration and time of administration, was assessed through self-administered questionnaires. We used Cox proportional hazards regression models adjusted for age and melanoma risk factors. Over 1990-2008, about 611 melanoma cases were ascertained among 86 653 women. Compared with never use, ever use of FDs was not associated with melanoma risk overall [hazard ratio (HR) = 1.15; 95% confidence interval (CI) = 0.75-1.74], or among parous women (HR = 1.08; 95% CI = 0.67-1.73). Among ever users of FDs, duration of use and age at first use were not associated with melanoma risk. Associations were similar after adjustment for UV exposure, although FD users were more likely to report tanning bed use than never-users (odds ratio = 1.50; CI = 1.01-2.22) in a subsample with recreational UV exposure data. Our data do not support an association between FD use and melanoma risk, but underlie the importance of taking into consideration potential confounding from sun exposure in future research.

The role of hormonal factors in the etiology of lymphoid neoplasms remains unclear. Previous studies have yielded conflicting results, have lacked sufficient statistical power to assess many lymphoma subtypes, or have lacked detailed information on relevant exposures. Within the European Prospective Investigation Into Cancer and Nutrition cohort, we analyzed comprehensive data on reproductive factors and exogenous hormone use collected at baseline (1992–2000) among 343,458 women, including data on 1,427 incident cases of B-cell non-Hodgkin lymphoma (NHL) and its major subtypes identified after a mean follow-up period of 14 years (through 2015). We estimated hazard ratios and 95% confidence intervals using multivariable proportional hazards modeling. Overall, we observed no statistically significant associations between parity, age at first birth, breastfeeding, oral contraceptive use, or ever use of postmenopausal hormone therapy and risk of B-cell NHL or its subtypes. Women who had undergone surgical menopause had a 51% higher risk of B-cell NHL (based on 67 cases) than women with natural menopause (hazard ratio = 1.51, 95% confidence interval: 1.17, 1.94). Given that this result may have been due to chance, our results provide little support for the hypothesis that sex hormones play a role in lymphomagenesis.

Alcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex-hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol-consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol-related hormonal signature, obtained by Partial Least Square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct (NDE) and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor positive tumours with respectively TE=1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1-SD deviation increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE=1.03(1.00,1.06). However, an alcohol-related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone, was associated with BC risk (OR=1.25 (1.07,1.47)) for a 1-SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol-BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association. This article is protected by copyright. All rights reserved.

Source at https://doi.org/10.1002/ijc.31854. 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.

OBJECTIVES In this study, we attempt to describe the profile of sunbed users among cancer-free French women. METHODS E3N is a prospective cohort including 98,995 French women aged 40- 65 years in 1990. In 2008, a specific UV questionnaire was sent to all reported skin cancer cases and 3 controls per case, matched on age, county of birth, and education. We used logistic regression models adjusted for pigmentary traits. RESULTS Compared with non-users, ever-users of sunbeds were younger (ptrend < .0001), had higher levels of education (ptrend = .0004) and income (ptrend = .002), and were more likely to be divorced/separated (OR = 1.58). They were more likely to be smokers (OR = 1.59) or former smokers (OR = 1.64), had higher alcohol intakes (ptrend = .001), and lower physical activity levels (OR = 0.54), although they had a lower BMI (ptrend = .004) and a thinner body shape (ptrend = .006). Sunbed users were also more likely to report many freckles (ptrend = .01) and sunburns in adulthood (ptrend = .008), to use sunscreen (SPF

In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma, however epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a multi-centre prospective study that enrolled over 500,000 participants aged 25-70 years from ten European countries in 1992-2000. Information on coffee and tea drinking was collected at baseline using validated country-specific dietary questionnaires. We used adjusted Cox proportional hazards regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between coffee and tea consumption and melanoma risk. Overall, 2,712 melanoma cases were identified during a median follow-up of 14.9 years among 476,160 study participants. Consumption of caffeinated coffee was inversely associated with melanoma risk among men (HR for highest quartile of consumption vs. non-consumers 0.31, 95% CI 0.14-0.69) but not among women (HR 0.96, 95% CI 0.62-1.47). There were no statistically significant associations between consumption of decaffeinated coffee or tea and the risk of melanoma among both men and women. The consumption of caffeinated coffee was inversely associated with melanoma risk among men in this large cohort study. Further investigations are warranted to confirm our findings and clarify the possible role of caffeine and other coffee compounds in reducing the risk of melanoma., In France, the E3N study was financially supported by the Mutuelle Générale de l'Education Nationale (MGEN), the European Community, the French League Against Cancer (LNCC); Gustave Roussy; and the French Institute of Health and Medical research (INSERM). EPIC-Greece was supported by the Hellenic Health Foundation. Support for EPIC Norfolk is from Medical Research Council UK and Cancer Research UK. EPIC-Italy was supported by the Italian Association for Cancer Research (AIRC).

Background and aims Skin cancers are the most common cancers in Caucasian populations worldwide and their incidence is rising. Ultraviolet radiation (UV) exposure is currently the sole environmental factor on which skin cancer prevention can be based. Given the oxidant effects of UV leading to skin carcinogenesis, dietary consumption of antioxidants has been proposed to reduce skin cancer risk. However, previous findings were inconsistent. The Mediterranean diet (MD) has long been reported to reduce the risk of several diseases including cancers. While previous studies explored the relationships between major food groups or individual dietary components of the MD and skin cancer risk, no previous study has investigated adherence to a MD pattern in relation to skin cancer risk to date. Methods E3 N is an ongoing prospective cohort of 98,995 French women aged 40–65 years at inclusion in 1990. Participants completed self-administered questionnaires sent biennially. Skin cancer cases were confirmed through pathology reports. Dietary data were collected via a validated food frequency questionnaire in 1993. Adherence to a MD pattern was assessed using the 9-unit dietary score proposed by Trichopoulou et al. in 2005, which takes values from 0 to 9 points (minimum to maximum adherence) according to the combined intake of fruits, vegetables, legumes, cereals, lipids, fish, dairy products, meat products, and alcohol. In this revised version of the MD score, lipid intake was assessed by calculating the ratio of unsaturated (i.e. mono- and polyunsaturated) to saturated fatty acids. We used Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (CI) adjusted for age, birth cohort, pigmentary traits, residential UV exposure at birth and at inclusion, family history of skin cancer, total energy intake, body mass index, physical activity, smoking status, education and coffee intake. Results Between 1993 and 2008, 404 melanoma, 232 squamous-cell carcinoma (SCC), and 1367 basal-cell carcinoma (BCC) cases were ascertained among the 67,332 included women. The MD score distribution was as follows: Tertile 1: 0–3 (29.4%), Tertile 2: 4–5 (45.2%) and Tertile 3: 6–9 (25.4%). Adherence to the MD was associated with an overall reduction in skin cancer risk (HR = 0.87, 95% CI = 0.77–0.97 for T3 vs.T1, P-trend = 0.01; HR = 0.96, 95% CI = 0.94–0.99 per unit increase in the MD score). When considering skin cancer type, there was a linear inverse association between MD score and risk of non-melanoma skin cancers (HR = 0.87, 95% CI = 0.76–0.99, P-trend = 0.04), particularly BCC (HR = 0.84, 95% CI = 0.72–0.97, P-trend = 0.01). However, while we found no evidence of a linear association with melanoma (P-trend = 0.08), we observed that high MD scores were associated with a borderline reduced risk of melanoma (HR = 0.76, 95% CI = 0.57–1.00) compared with the lowest scores. Moreover, there was no heterogeneity detected across skin cancer types (Pheterogenity = 0.23). Conclusion In this large prospective cohort study, adherence to the MD was linearly associated with a reduction in overall skin cancer risk, mostly driven by an inverse association with BCC; in addition, a high MD score was associated with a decreased melanoma risk. These results suggest that a high level of adherence to the MD pattern may confer protection against skin cancer in women. If confirmed in future research, these findings may ultimately provide additional knowledge for skin cancer prevention.

Introduction Evidence suggests that cutaneous melanoma, the most lethal form of skin cancer, may be influenced by sex hormones. Oral hormones are the leading contraception method in industrialized countries and represent a significant source of exogenous hormone use. Several studies reported a positive association between oral contraceptive (OC) use and melanoma risk. However, findings were conflicting and data from large prospective studies are lacking. Our aim was to explore the associations between OC use and melanoma risk in women. Methods E3 N is a prospective cohort of 98,995 French women aged 40–65 years at inclusion in 1990. Use of oral hormones for contraception was collected through a self-administered questionnaire at baseline, and detailed information on lifetime use of OCs was then recorded every 2–3 years from 1992. We computed hazard ratios (HRs) and 95% Confidence Intervals (CIs) using Cox regression models adjusted for age, birth cohort, pigmentary traits, residential UV exposure in county of birth and at inclusion, and family history of skin cancer. We stratified the results according to melanoma site and histological type using competing-risk models. To examine potential confounding by sun exposure, we used data from E3N-SunExp, a nested case-control study in which a specific questionnaire on lifetime residential and recreational UV exposures was sent to all incident skin cancer cases and 3 controls per case (matched on age, county of birth, education, and length of follow-up in the cohort) in 2008. Analyses in the sub-cohort were performed through logistic regression modelling. Results Between 1992 and 2008, 539 melanoma cases were ascertained among 79,365 women. In age-adjusted models, there was a modest association between ever use of OCs and melanoma risk (HR = 1.18, 95% CI = 0.98–1.42), which was reduced after full adjustment (HR = 1.14, 95% CI = 0.95–1.38). The association was stronger in long-term users (HR = 1.33, 95% CI = 1.00–1.75 for a duration of use of at least 10 years, compared with never use of OCs). Among ever users, there was an inverse association with age at first use (Ptrend = 0.01), consistent with longer durations of OC use in women with a younger age at first use. However, we found no evidence of an association with age at last use or time since last use. When exploring different formulations, the association between ever use of OCs and melanoma risk was restricted to OCs containing high doses of estrogen (≥ 50 μg of ethinyl estradiol) (HR = 1.26, CI = 1.03–1.53). In subtype- and site-specific analyses, ever use of OCs appeared positively associated with all types and sites of melanoma, except the trunk, although no heterogeneity was detected across subtypes (Phomogeneity = 0.54) or sites (Phomogeneity = 0.23). In the E3N-SunExp population, associations between OC use and melanoma risk were not substantially modified after adjustment for residential or recreational UV exposure. However, while we found no association between OC use and sun exposure, we observed that OC use was positively associated with sunscreen use (Ptrend = 0.04 from no protection to increasing SPF) and tanning bed use (odds ratio = 1.14, 95% CI = 1.01–1.29 for ever vs. never use), even after adjusting for age and year of birth. Conclusions Overall, our findings do not support a strong association between OC use and melanoma risk. OC users were more likely to use sunscreen and tanning beds, suggesting a specific profile of OC users regarding their attitude towards tanning. Therefore, we cannot exclude that the observed relation between OC use and melanoma risk, which has been debated in the literature for almost 40 years, could relate to particular sun exposure behaviors in users. Further research, including social and behavioral description of OC users, is thus critical to increase our understanding of the risk profile of women diagnosed with melanoma, and to question the hypothesis of a hormonal influence on melanoma risk.

Background and aims Experimental studies suggest that antioxidants could protect against skin carcinomas. However, epidemiological studies on dietary antioxidant supplement use in relation to risk of basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) yielded inconsistent findings, and very few prospective studies with available sun exposure data have been conducted to date. Our objective was to investigate the relationships between the use of dietary supplements in beta-carotene, and vitamins A, C, and E, and risk of non-melanoma skin cancers (NMSC). Methods E3 N is an ongoing prospective cohort involving 98,995 French women aged 40–65 years at inclusion in 1990. Data on the occurrence of BCC and SCC were collected every 2–3 years through self-administered questionnaires, with skin cancer cases confirmed through pathology reports. Intake of specific antioxidant supplements was collected in 1995. Dietary antioxidant intakes from foods were calculated using data collected via a validated food frequency questionnaire in 1993. We used Cox proportional hazards regression models with age as the time scale to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the risks of BCC and SCC associated with antioxidant supplement use. Models were adjusted for age, birth cohort, pigmentary traits, residential UV exposure at birth and at inclusion, family history of skin cancer, body mass index, physical activity, smoking status, and education. Results Over a mean follow-up of 11.6 years, 1245 BCC and 219 SCC cases were diagnosed among the 63,077 included women. We observed a positive association between vitamin A supplement use and risk of NMSCs (HR = 1.30, 95% CI: 1.02–1.67), particularly BCC (HR = 1.32, 95% CI: 1.01–1.72). There was also a positive association between vitamin E supplement use and NMSC risk (HR = 1.28; 95% CI: 1.05–1.56). Moreover, we found an interaction between vitamin A supplement use and dietary intake of retinol (Pinteraction = 0.04) on the risk of NSMCs: vitamin A supplement use was associated with an increased risk of NMSCs only in women in the highest tertile of dietary retinol intake (HR = 1.89; 95% CI: 1.29–2.75), but not in those in the middle (HR = 1.05, 95% CI: 0.64–1.74) or lowest tertiles of intake (HR = 1.10; 95% CI: 0.70–1.73). However, use of beta-carotene or vitamin C supplements was not associated with NMSC risk. Conclusion Our study suggests an increased risk of NMSCs associated with vitamin A (particularly for BCC) and vitamin E supplement use. The increased risk associated with vitamin A supplement use was restricted to women with high intakes of retinol from foods. These findings suggest that high supplementary intakes of some antioxidants could confer a higher risk of NMSCs in women, particularly in the context of high antioxidant intakes in the diet in the case of retinol. More research is warranted in order to replicate these findings and investigate their underlying mechanisms.