Maria Dolores Chirlaque

Adherence to the Mediterranean Diet and Risk of Coronary Heart Disease in the Spanish EPIC Cohort Study

No known cohort study has investigated whether the Mediterranean diet can reduce incident coronary heart disease (CHD) events in a Mediterranean population. This study examined the relation between Mediterranean diet adherence and risk of incident CHD events in the 5 Spanish centers of the European Prospective Investigation into Cancer and Nutrition. Analysis included 41,078 participants aged 29-69 years, recruited in 1992-1996 and followed up until December 2004 (mean follow-up:10.4 years). Confirmed incident fatal and nonfatal CHD events were analyzed according to Mediterranean diet adherence, measured by using an 18-unit relative Mediterranean diet score. A total of 609 participants (79% male) had a fatal or nonfatal confirmed acute myocardial infarction (n = 468) or unstable angina requiring revascularization (n = 141). After stratification by center and age and adjustment for recognized CHD risk factors, high compared with low relative Mediterranean diet score was associated with a significant reduction in CHD risk (hazard ratio = 0.60, 95% confidence interval: 0.47, 0.77). A 1-unit increase in relative Mediterranean diet score was associated with a 6% reduced risk of CHD (95% confidence interval: 0.91, 0.97), with similar risk reductions by sex. Mediterranean diet adherence was associated with a significantly reduced CHD risk in this Mediterranean country, supporting its role in primary prevention of CHD in healthy populations.

Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study

Objective To compute the burden of cancer attributable to current and former alcohol consumption in eight European countries based on direct relative risk estimates from a cohort study. Design Combination of prospective cohort study with representative population based data on alcohol exposure. Setting Eight countries (France, Italy, Spain, United Kingdom, the Netherlands, Greece, Germany, Denmark) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Participants 109 118 men and 254 870 women, mainly aged 37-70. Main outcome measures Hazard rate ratios expressing the relative risk of cancer incidence for former and current alcohol consumption among EPIC participants. Hazard rate ratios combined with representative information on alcohol consumption to calculate alcohol attributable fractions of causally related cancers by country and sex. Partial alcohol attributable fractions for consumption higher than the recommended upper limit (two drinks a day for men with about 24 g alcohol, one for women with about 12 g alcohol) and the estimated total annual number of cases of alcohol attributable cancer. Results If we assume causality, among men and women, 10% (95% confidence interval 7 to 13%) and 3% (1 to 5%) of the incidence of total cancer was attributable to former and current alcohol consumption in the selected European countries. For selected cancers the figures were 44% (31 to 56%) and 25% (5 to 46%) for upper aerodigestive tract, 33% (11 to 54%) and 18% (−3 to 38%) for liver, 17% (10 to 25%) and 4% (−1 to 10%) for colorectal cancer for men and women, respectively, and 5.0% (2 to 8%) for female breast cancer. A substantial part of the alcohol attributable fraction in 2008 was associated with alcohol consumption higher than the recommended upper limit: 33 037 of 178 578 alcohol related cancer cases in men and 17 470 of 397 043 alcohol related cases in women. Conclusions In western Europe, an important proportion of cases of cancer can be attributable to alcohol consumption, especially consumption higher than the recommended upper limits. These data support current political efforts to reduce or to abstain from alcohol consumption to reduce the incidence of cancer.

Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition

Endometrial cancer risk has been associated with reproductive factors (age at menarche, age at menopause, parity, age at first and last birth, time since last birth and use of oral contraceptives (OCs)]. However, these factors are closely interrelated and whether they act independently still requires clarification. We conducted a study to examine the association of menstrual and reproductive variables with the risk of endometrial cancer among the European Prospective Investigation into Cancer and Nutrition (EPIC). Among the 302,618 women eligible for the study, 1,017 incident endometrial cancer cases were identified. A reduction in endometrial cancer risk was observed in women with late menarche, early menopause, past OC use, high parity and a shorter time since last full‐term pregnancy (FTP). No association was observed for duration of breast feeding after adjustment for number of FTP or for abortion (spontaneous or induced). After mutual adjustment, late age at menarche, early age at menopause and duration of OC use showed similar risk reductions of 7–8% per year of menstrual life, whereas the decreased risk associated with cumulative duration of FTPs was stronger (22% per year). In conclusion, our findings confirmed a reduction in risk of endometrial cancer with factors associated with a lower cumulative exposure to estrogen and/or higher exposure to progesterone, such as increasing number of FTPs and shorter menstrual lifespan and, therefore, support an important role of hormonal mechanisms in endometrial carcinogenesis.

Estimation of Dietary Sources and Flavonoid Intake in a Spanish Adult Population (EPIC-Spain)

BACKGROUND Epidemiologic studies have suggested associations between flavonoid intake and health benefits. Traditional Mediterranean diets consist of a high consumption of plant products rich in flavonoids. OBJECTIVE This study estimates dietary flavonoid intake and main food sources in a Mediterranean population (Spanish adults). DESIGN The study included 40,683 subjects aged 35 to 64 years from northern and southern regions of Spain who were included in the European Prospective Investigation into Cancer and Nutrition study Spanish cohort. Usual food intake was assessed by personal interviews using a computerized version of a validated diet history method. Expanded US Department of Agriculture databases for the flavonoid, isoflavone, and proanthocyanidin content were used. RESULTS The median and mean of total flavonoids were 269.17 and 313.26 mg/day, respectively. The most abundant flavonoid subgroup was proanthocyanidins (60.1%), followed by flavanones (16.9%), flavan-3-ols (10.3%), flavonols (5.9%), anthocyanidins (5.8%), flavones (1.1%), and isoflavones (<0.01%). The main sources of total flavonoid intake were apples (23%), red wine (21%), unspecified fruit (12.8%), and oranges (9.3%). CONCLUSIONS These results should be very useful for evaluating the relationships between flavonoid intake and several diseases.

Anthropometric measures, endogenous sex steroids and breast cancer risk in postmenopausal women: A study within the EPIC cohort

In a large case–control study on breast cancer risk and serum hormone concentrations, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we examined to what extent the relationship of excess body weight with breast cancer risk may be explained by changes in sex steroids. Height, weight, waist and hip circumferences, and serum measurements of testosterone [T], androstenedione [Δ4], dehydroepiandrosterone sulphate [DHEAS], estradiol [E2], estrone [E1] and sex‐hormone binding globulin [SHBG] were available for 613 breast cancer cases, and 1,139 matched controls, who were all menopausal at the time of blood donation. Free T [fT] and free E2 [fE2] were calculated using mass action equations. Breast cancer risk was related to body mass index (BMI) (RR = 1.11 [0.99–1.25], per 5 kg/m2 increase in BMI), and waist (RR = 1.12 [1.02–1.24], per 10 cm increase) and hip circumferences (RR = 1.14 [1.02–1.27], per 10 cm increase). The increase in breast cancer risk associated with adiposity was substantially reduced after adjustment for any estrogens, especially for fE2 (from 1.11 [0.99–1.25] to 0.99 [0.87–1.12], from 1.12 [1.02–1.24] to 1.02 [0.92–1.14] and from 1.14 [1.02–1.27] to 1.05 [0.93–1.18] for BMI, waist and hip circumferences, respectively). A modest attenuation in excess risk was observed after adjustment for fT, but the remaining androgens had little effect on the association of body adiposity with breast cancer. Our data indicate that the relationship of adiposity with breast cancer in postmenopausal women could be partially explained by the increases in endogenous estrogens, and by a decrease in levels of SHBG.

Eating out of home and its correlates in 10 European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC) study

OBJECTIVE To compare the average out-of-home (OH) consumption of foods and beverages, as well as energy intake, among populations from 10 European countries and to describe the characteristics of substantial OH eaters, as defined for the purpose of the present study, in comparison to other individuals. DESIGN Cross-sectional study. Dietary data were collected through single 24-hour dietary recalls, in which the place of consumption was recorded. For the present study, substantial OH eaters were defined as those who consumed more than 25% of total daily energy intake at locations other than the household premises. Mean dietary intakes and the proportion of substantial OH eaters are presented by food group and country. Logistic regression analyses were used to estimate the odds of being a substantial OH eater in comparison to not being one, using mutually adjusted possible non-dietary determinants. SETTING Ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS The subjects were 34 270 individuals, 12 537 men and 21 733 women, aged 35-74 years. RESULTS The fraction of energy intake during OH eating was generally higher in northern European countries than in the southern ones. Among the food and beverage groups, those selectively consumed outside the home were coffee/tea/waters and sweets and, to a lesser extent, cereals, meats, added lipids and vegetables. Substantial OH eating was positively associated with energy intake and inversely associated with age and physical activity. Substantial OH eating was less common among the less educated compared with the more educated, and more common during weekdays in central and north Europe and during the weekend in south Europe. CONCLUSIONS Eating outside the home was associated with sedentary lifestyle and increased energy intake; it was more common among the young and concerned in particular coffee/tea/waters and sweets.

Body Size and Risk of Prostate Cancer in the European Prospective Investigation into Cancer and Nutrition

Background: Body size has been hypothesized to influence the risk of prostate cancer; however, most epidemiologic studies have relied on body mass index (BMI) to assess adiposity, whereas only a few studies have examined whether body fat distribution predicts prostate cancer. Methods: We examined the association of height, BMI, waist and hip circumference, and waist-hip ratio with prostate cancer risk among 129,502 men without cancer at baseline from 8 countries of the European Prospective Investigation into Cancer and Nutrition (EPIC), using Cox regression, with age as time metric, stratifying by study center and age at recruitment, and adjusting for education, smoking status, alcohol consumption, and physical activity. Results: During a mean follow-up of 8.5 years, 2,446 men developed prostate cancer. Waist circumference and waist-hip ratio were positively associated with risk of advanced disease. The relative risk of advanced prostate cancer was 1.06 (95% confidence interval, 1.01-1.1) per 5-cm-higher waist circumference and 1.21 (95% confidence interval, 1.04-1.39) per 0.1-unit-higher waist-hip ratio. When stratified by BMI, waist circumference and waist-hip ratio were positively related to risk of total, advanced, and high-grade prostate cancer among men with lower but not among those with higher BMI (Pinteraction for waist with BMI, 0.25, 0.02, and 0.05, respectively; Pinteraction for waist-hip ratio with BMI, 0.27, 0.22, and 0.14; respectively). Conclusions: These data suggest that abdominal adiposity may be associated with an increased risk of advanced prostate cancer. This association may be stronger among individuals with lower BMI; however, this finding needs confirmation in future studies. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3252–61)

Dietary sources of vitamin C, vitamin E and specific carotenoids in Spain

A cross-sectional study was conducted within the Spanish cohort of the European Prospective Investigation in Cancer and Nutrition to assess the principal food sources of vitamin C, vitamin E, alpha-carotene, beta-carotene, lycopene, lutein, beta-cryptoxanthin and zeaxanthin in an adult Spanish population. The study included 41446 healthy volunteers (25812 women and 15634 men), aged 29-69 years, from three Spanish regions in the north (Asturias, Navarra and Guipúzcoa) and two in the south (Murcia and Granada). Usual food intake was estimated by personal interview through a computerized version of a dietary history questionnaire. Foods that provided at least two-thirds of the studied nutrients were: fruits (mainly oranges) (51 %) and fruiting vegetables (mainly tomato and sweet pepper) (20 %) for vitamin C; vegetable oils (sunflower and olive) (40 %), non-citrus fruits (10 %), and nuts and seeds (8 %) for vitamin E; root vegetables (carrots) (82 %) for alpha-carotene; green leafy (28 %), root (24 %) and fruiting vegetables (22 %) for beta-carotene; fruiting vegetables (fresh tomato) (72 %) for lycopene; green leafy vegetables (64 %) for lutein; citrus fruits (68 %) for beta-cryptoxanthin; citrus fruits (43 %) and green leafy vegetables (20 %) for zeaxanthin. In conclusion, the main food sources of nutrients with redox properties have been identified in a Mediterranean country. This could provide an insight into the interpretation of epidemiological studies investigating the role of diet in health and disease.

Anthropometry and esophageal cancer risk in the European prospective investigation into cancer and nutrition

Background: Increasing evidence suggests that general obesity [measured by body mass index (BMI)] is positively associated with risk of esophageal adenocarcinoma (EAC). In contrast, previous studies have shown inverse relations with esophageal squamous cell carcinoma (ESCC). However, it is still unclear whether body fat distribution, particularly abdominal obesity, is associated with each type of esophageal cancer. Methods: We applied multivariable adjusted Cox proportional hazards regression to investigate the association between anthropometric measures and risk of EAC and ESCC among 346,554 men and women participating in the European Prospective Investigation into Cancer and Nutrition. All statistical tests were two sided. Results: During 8.9 years of follow-up, we documented 88 incident cases of EAC and 110 cases of ESCC. BMI, waist circumference, and waist-to-hip ratio (WHR) were positively associated with EAC risk [highest versus lowest quintile; relative risk (RR), 2.60; 95% confidence interval (95% CI), 1.23-5.51; Ptrend < 0.01; RR, 3.07; 95% CI, 1.35-6.98; Ptrend < 0.003; and RR, 2.12; 95% CI, 0.98-4.57; Ptrend < 0.004]. In contrast, BMI and waist circumference were inversely related to ESCC risk, whereas WHR showed no association with ESCC. In stratified analyses, BMI and waist circumference were significantly inversely related to ESCC only among smokers but not among nonsmokers. However, when controlled for BMI, we found positive associations for waist circumference and WHR with ESCC, and these associations were observed among smokers and nonsmokers. Conclusion: General and abdominal obesity were associated with higher EAC risk. Further, our study suggests that particularly an abdominal body fat distribution might also be a risk factor for ESCC. (Cancer Epidemiol Biomarkers Prev 2009;18(7):2079–89)

Concentrations of resveratrol and derivatives in foods and estimation of dietary intake in a Spanish population: European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort.

Resveratrol has been shown to have beneficial effects on diseases related to oxidant and/or inflammatory processes and extends the lifespan of simple organisms including rodents. The objective of the present study was to estimate the dietary intake of resveratrol and piceid (R&P) present in foods, and to identify the principal dietary sources of these compounds in the Spanish adult population. For this purpose, a food composition database (FCDB) of R&P in Spanish foods was compiled. The study included 40,685 subjects aged 35-64 years from northern and southern regions of Spain who were included in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort. Usual food intake was assessed by personal interviews using a computerised version of a validated diet history method. An FCDB with 160 items was compiled. The estimated median and mean of R&P intake were 100 and 933 microg/d respectively. Approximately, 32% of the population did not consume R&P. The most abundant of the four stilbenes studied was trans-piceid (53.6%), followed by trans-resveratrol (20.9%), cis-piceid (19.3%) and cis-resveratrol (6.2%). The most important source of R&P was wines (98.4%) and grape and grape juices (1.6%), whereas peanuts, pistachios and berries contributed to less than 0.01%. For this reason the pattern of intake of R&P was similar to the wine pattern. This is the first time that R&P intake has been estimated in a Mediterranean country.