Isabelle Savoye

Coffee, tea and melanoma risk: findings from the European Prospective Investigation into Cancer and Nutrition

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.

Patterns of Ultraviolet Radiation Exposure and Skin Cancer Risk: the E3N-SunExp Study

Background While ultraviolet (UV) radiation exposure is a recognized risk factor for skin cancer, associations are complex and few studies have allowed a direct comparison of exposure profiles associated with cutaneous melanoma, basal-cell carcinoma (BCC), and squamous-cell carcinoma (SCC) within a single population. Methods We examined associations between UV exposures and skin cancer risk in a nested case-control study within E3N, a prospective cohort of 98,995 French women born in 1925–1950. In 2008, a lifetime UV exposure questionnaire was sent to all reported skin cancer cases and three controls per case, which were matched on age, county of birth, and education. Analyses were performed using conditional logistic regression and included 366 melanoma cases, 1,027 BCC cases, 165 SCC cases, and 3,647 controls. Results A history of severe sunburns <25 years was associated with increased risks of all skin cancers (melanoma: OR 2.7; BCC: OR 1.7; SCC: OR 2.0 for ≥6 sunburns vs. none), while sunburns ≥25 years were associated with BCC and SCC only. While high-sun protection factor sunscreen use before age 25 was associated with lower BCC risk (Ptrend = 0.02), use since age 25 and reapplication of sunscreen were associated with higher risks of all three types of skin cancer. There were positive linear associations between total UV score and risks of BCC (Ptrend = 0.01) and SCC (Ptrend = 0.09), but not melanoma. While recreational UV score was strongly associated with BCC, total and residential UV scores were more strongly associated with SCC. Conclusions Melanoma, BCC, and SCC are associated with different sun exposure profiles in women.

Endometriosis and the risk of skin cancer: a prospective cohort study

PurposeEndometriosis 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.MethodsE3N is a prospective cohort of 98,995 French women aged 40–65xa0years in 1990. Data on surgically confirmed endometriosis and skin cancer diagnoses were collected every 2–3xa0years 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.ResultsBetween 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 (Phomogeneityxa0=xa00.13).ConclusionThese 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.

Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Adequate intake of copper and zinc, two essential micronutrients, are important for antioxidant functions. Their imbalance may have implications for development of diseases like colorectal cancer (CRC), where oxidative stress is thought to be etiologically involved. As evidence from prospective epidemiologic studies is lacking, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to investigate the association between circulating levels of copper and zinc, and their calculated ratio, with risk of CRC development. Copper and zinc levels were measured by reflection X-ray fluorescence spectrometer in 966 cases and 966 matched controls. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression and are presented for the fifth versus first quintile. Higher circulating concentration of copper was associated with a raised CRC risk (OR = 1.50; 95% CI: 1.06, 2.13; P-trend = 0.02) whereas an inverse association with cancer risk was observed for higher zinc levels (OR = 0.65; 95% CI: 0.43, 0.97; P-trend = 0.07). Consequently, the ratio of copper/zinc was positively associated with CRC (OR = 1.70; 95% CI: 1.20, 2.40; P-trend = 0.0005). In subgroup analyses by follow-up time, the associations remained statistically significant only in those diagnosed within 2 years of blood collection. In conclusion, these data suggest that copper or copper levels in relation to zinc (copper to zinc ratio) become imbalanced in the process of CRC development. Mechanistic studies into the underlying mechanisms of regulation and action are required to further examine a possible role for higher copper and copper/zinc ratio levels in CRC development and progression.

A prospective evaluation of plasma polyphenol levels and colon cancer risk

Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre‐diagnostic plasma polyphenols and colon cancer risk in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition study. Using high pressure liquid chromatography coupled to tandem mass spectrometry, we measured concentrations of 35 polyphenols in plasma from 809 incident colon cancer cases and 809 matched controls. We used multivariable adjusted conditional logistic regression models that included established colon cancer risk factors. The false discovery rate (qvalues) was computed to control for multiple comparisons. All statistical tests were two‐sided. After false discovery rate correction and in continuous log2‐transformed multivariable models, equol (odds ratio [OR] per log2‐value, 0.86, 95% confidence interval [95% CI]u2009=u20090.79–0.93; qvalueu2009=u20090.01) and homovanillic acid (OR per log2‐value, 1.46, 95% CIu2009=u20091.16–1.84; qvalueu2009=u20090.02) were associated with colon cancer risk. Comparing extreme fifths, equol concentrations were inversely associated with colon cancer risk (ORu2009=u20090.61, 95% CIu2009=u20090.41–0.91, ptrendu2009=u20090.003), while homovanillic acid concentrations were positively associated with colon cancer development (ORu2009=u20091.72, 95% CIu2009=u20091.17–2.53, ptrendu2009<u20090.0001). No heterogeneity for these associations was observed by sex and across other colon cancer risk factors. The remaining polyphenols were not associated with colon cancer risk. Higher equol concentrations were associated with lower risk, and higher homovanillic acid concentrations were associated with greater risk of colon cancer. These findings support a potential role for specific polyphenols in colon tumorigenesis.

Well-being, gender, and psychological health in school-aged children

BackgroundDespite being a well-documented phenomenon, gender differences in psychological health complaints in adolescence are poorly understood. The purpose of this study was to test factors related to well-being as explanatory factors of gender differences in psychological complaints (feeling low, irritability or bad temper, nervousness, and sleeping difficulties) in adolescence.MethodsThis study was based on the 9th Health Behaviour in School-aged Children (HBSC) study, conducted in 2010 in the Wallonia-Brussels Federation, Belgium, on 9–24 year olds. Using logistic regression analyses, we studied gender differences in psychological complaints through well-being factors (life satisfaction, self-confidence, helplessness, and body image), across age categories, and examined the variation of female excess after taking into account each factor.ResultsThe four well-being factors together explained more than half of the female excess in feeling low. However, there were still significant gender differences in feeling low for children over 13. Among 13 to 15-year-olds, there were no gender differences in irritability after adjustment. An important decrease in gender differences in nervousness was observed in the multivariate analyses, although there was still significant female excess in nervousness increasing from 13 years old. After full adjustment, only gender differences in sleeping difficulties among 13–15-year-olds remained significant. For all psychological complaints studied, self-confidence caused the most important decrease in gender difference.ConclusionsThis study showed that factors related to well-being could mediate the association between gender and psychological complaints, and pointed to the importance of taking into account well-being factors in the analyses of the aetiology of gender differences in psychological complaints. However, our results suggested that future research should explore additional explanations for gender differences in psychological complaints.

Oral contraceptive use and cutaneous melanoma risk: a French prospective cohort study: Oral contraceptive use and cutaneous melanoma risk

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.

Is melanoma survival influenced by month of diagnosis

BACKGROUNDnDespite being a well-documented phenomenon, seasonal variation in the incidence of cutaneous melanoma is poorly understood, and data on the seasonality of melanoma survival are scarce. We sought to explore the seasonal variation in melanoma incidence and survival in Belgium and to assess the characteristics and outcomes of cases diagnosed during the seasonal peak.nnnMETHODSnAll cases of invasive cutaneous melanoma-patients over 15 years of age and registered by the Belgian Cancer Registry (BCR) from 2004 to 2009-were included (n=9782). Monthly variations in incidence were estimated by the ratio of the number of cases diagnosed each month to that diagnosed in January (Rmonth/January) using Nams method. The observed and relative 5-year survival rates were adjusted on patient and tumour characteristics using Cox proportional hazards regression models and generalised linear models with a Poisson error structure, respectively.nnnRESULTSnA peak in melanoma incidence was observed in June (RJune/January=1.64, 95% confidence interval (CI)=1.54-1.73). The 5-year observed survival (OS) and relative survival (RS) rates were significantly higher for patients diagnosed in June compared with other months (OSJune=84%, 95%CI=81-86 versus OSOthermonths=79%, 95%CI=78-80; RSJune=93%, 95%CI=90-95 versus RSothermonths=87%, 95%CI=86-88). After adjustment, the 5-year OS remained significantly higher for patients diagnosed in June (hazard ratioJune=0.78, 95%CI=0.62-0.98); however, the 5-year RS was no longer significantly different for patients diagnosed in June compared with other months (relative excess riskJune=1.16, 95%CI=0.73-1.84).nnnCONCLUSIONSnThis study demonstrated a seasonal variation in melanoma incidence in Belgium with a peak in June for the period 2004-2009. When adjusted for patient and tumour characteristics, patients diagnosed in June had higher observed survival rates, but relative survival rates did not differ. Our findings do not support an influence of season of diagnosis on melanoma prognosis.