Plasma phyto-oestrogens and prostate cancer in the European Prospective Investigation into Cancer and Nutrition.

We examined plasma concentrations of phyto-oestrogens in relation to risk for subsequent prostate cancer in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition. Concentrations of isoflavones genistein, daidzein and equol, and that of lignans enterolactone and enterodiol, were measured in plasma samples for 950 prostate cancer cases and 1042 matched control participants. Relative risks (RRs) for prostate cancer in relation to plasma concentrations of these phyto-oestrogens were estimated by conditional logistic regression. Higher plasma concentrations of genistein were associated with lower risk of prostate cancer: RR among men in the highest vs the lowest fifth, 0.71 (95% confidence interval (CI) 0.53-0.96, P trend=0.03). After adjustment for potential confounders this RR was 0.74 (95% CI 0.54-1.00, P trend=0.05). No statistically significant associations were observed for circulating concentrations of daidzein, equol, enterolactone or enterodiol in relation to overall risk for prostate cancer. There was no evidence of heterogeneity in these results by age at blood collection or country of recruitment, nor by cancer stage or grade. These results suggest that higher concentrations of circulating genistein may reduce the risk of prostate cancer but do not support an association with plasma lignans.

Dietary fat and breast cancer risk in the Swedish women's lifestyle and health cohort.

We investigated whether dietary intakes of total fat, monounsaturated fat (MUFA), polyunsaturated fat (PUFA) and saturated fat (SFA) were associated with breast cancer risk in a prospective cohort of 49 261 Swedish women (30-49 years at enrolment), which yielded 974 breast cancer cases by December 2005. Further, we evaluated if associations differed by oestrogen and/or progesterone receptor tumour status. Total fat, MUFA, PUFA or SFA were not associated with risk overall. However, women in the highest MUFA and PUFA quintile intake had a reduced breast cancer risk after age 50 years (hazard ratios: 95% confidence interval=0.45: 0.25-0.99 and 0.54: 0.35-0.85, respectively) compared to women in the lowest quintile. The associations did not differ by oestrogen or progesterone receptor status. Despite the negative findings, type of fat during premenopausal years may have later differential effects on risk.

Intake of specific flavonoid classes and coronary heart disease--a case-control study in Greece.

OBJECTIVE: Dietary intake of flavonoids has been reported to protect against coronary heart disease (CHD) risk, but associations of specific classes of flavonoids with CHD have not been adequately studied. DESIGN: Hospital-based case-control study relying on interviewer administered questionnaires. SETTING: Cardiology Department of the University of Athens Medical School in the Hippokrateion General Hospital (1990-1991). SUBJECTS: Cases were 329 patients with electrocardiographically confirmed first coronary infarct or a first positive coronary arteriogram, or both (participation fraction 93%). Controls were 570 patients admitted to the same hospital for minor conditions unrelated to nutrition (participation fraction 95%). All cases and controls were interviewed in the hospital wards by experienced interviewers, and a 110-item food frequency questionnaire was administered. RESULTS: There was statistically significant evidence (P approximately 0.03) for an inverse association between intake of flavan-3-ols and CHD risk, an increase of about 21 mg per day corresponding to a 24% decrease in CHD risk. The inverse association between flavan-3-ols and CHD risk was largely accounted for by the intake of wine and to a lesser extent tea. For none of the other flavonoid classes was there statistically significant evidence of an association. CONCLUSION: Flavan-3-ols, which are largely found in wine and tea, are inversely associated with, and may be protective against, coronary heart disease.

Does coffee protect against hepatocellular carcinoma?

We analysed the relation between coffee consumption and hepatocellular carcinoma in two case-control studies conducted between 1984 and 1998 in Italy and Greece, including 834 cases and 1912 controls. Compared to non coffee drinkers, the multivariate odds ratio was 0.7 for drinkers of three or more cups per day.

Cancer and Mediterranean dietary traditions.

The incidence of cancer overall in Mediterranean countries is lower than in Scandinavian countries, the United Kingdom, and the United States. This is mostly accounted for by the lower incidence among Mediterranean countries of cancer of the large bowel, breast, endometrium, and prostate. These forms of cancer have been linked to dietary factors, particularly low consumption of vegetables and fruit, and to a certain extent, high consumption of meat. The traditional Mediterranean diet is characterized by high consumption of foods of plant origin, relatively low consumption of red meat, and high consumption of olive oil, which in several studies has been reported to be more beneficial against cancer than other forms of added lipids. By taking into account the established or presumed nutritional causation of major forms of cancer and the composition of the traditional Mediterranean diet, estimates can be derived concerning the fraction of cancer occurrence in highly developed Western countries that could be attributed to their diets in comparison with the healthy traditional Mediterranean diet. Although estimates can only be crude, it can be calculated that up to 25% of the incidence of colorectal cancer, approximately 15% of the incidence of breast cancer, and approximately 10% of the incidence of prostate, pancreas, and endometrial cancer could be prevented if the populations of highly developed Western countries could shift to the traditional healthy Mediterranean diet.

Fraction of prostate cancer incidence attributed to diet in Athens, Greece.

Diet appears to be a major determinant in the incidence of prostate cancer. In a case-control study conducted in Athens, Greece, we found that dairy products, butter and seed oils were positively associated with risk of prostate cancer, whereas cooked and raw tomatoes were inversely associated. We utilized the data from this study to calculate the population attributable fractions under alternative assumptions of feasible dietary changes. For each subject, a dietary score was calculated and categorized into approximately quintiles, representing increasing levels of prostate cancer risk as a function of the intake of the five discriminatory food groups or items. Population attributable fractions in terms of this dietary score were calculated taking into account multivariate adjustment. We observed that, if all individuals were shifted to the baseline category, the incidence of prostate cancer in this study population would be reduced by 41% (95% confidence interval 23-59%). However, if all individuals were shifted to the adjacent lower risk quintile, the expected incidence reduction would be a more modest 19%. The incidence of prostate cancer in Greece could be reduced by about two-fifths if the population increased the consumption of tomatoes and reduced the intake of dairy products, and substituted olive oil for other added lipids.

Food groups and risk of squamous cell esophageal cancer in northern Italy.

To better understand the nutritional etiology of squamous cell esophageal cancer, we conducted a case-control study in 3 areas of northern Italy. A total of 304 incident, histologically confirmed cases of squamous cell carcinoma of the esophagus (275 men, 29 women) and 743 hospital controls (593 men, 150 women) with acute, non-neoplastic conditions, not related to smoking, alcohol consumption or long-term diet modification, were interviewed during 1992 to 1997. The validated food-frequency questionnaire included 78 questions on food items or recipes, which were then categorized into 19 main food groups, and 10 questions on fat intake pattern. After allowance for age, sex, education, area of residence, tobacco smoking, alcohol drinking and non-alcohol energy, a significant increased risk emerged for high consumption of soups (OR=2.1 for the highest vs. lowest quintile), whereas inverse associations with esophageal cancer risk were observed for pasta and rice (OR=0.7), poultry (OR=0.4), raw vegetables (OR=0.3), citrus fruit (OR=0.4) and other fruit (OR=0.5). The associations with dietary habits were consistent in different strata of tobacco smoking and alcohol drinking. Among added lipids, olive oil intake showed a significant reduction of esophageal cancer risk, even after allowance for total vegetable consumption (OR=0.4), while butter consumption was directly associated with this risk (OR=2.2). Our results thus provide further support to the evidence that raw vegetables and citrus fruit are inversely related to the risk of squamous cell esophageal cancer and suggest that olive oil may also reduce this risk.

Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma.

During a 4-year period from January 1995 to December 1998, blood samples and questionnaire data were obtained from 333 incident cases of hepatocellular carcinoma (HCC), as well as from 360 controls who were hospitalized for eye, ear, nose, throat or orthopedic conditions in Athens, Greece. Coded sera were tested for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) by third-generation enzyme immunoassays, and information on smoking habits and beverage consumption was obtained. We found a significant dose-response, positive association between smoking and HCC risk [>/= 2 packs per day, odds ratio (OR)=2.5]. This association was stronger in individuals without chronic infection with either HBV or HCV (>/= 2 packs per day, OR=2.8). Consumption of alcoholic beverages above a threshold of 40 glasses per week increased the risk of HCC (OR=1.9). We also found evidence of a strong, statistically significant and apparently super-multiplicative effect of heavy smoking and heavy drinking in the development of HCC (OR for both exposures=9.6). This interaction was particularly evident among individuals without either HBsAg or anti-HCV (OR for both exposures=10.9). Coffee intake was not positively associated with HCC risk, but the reverse could not be excluded for the subgroup of chronically infected individuals. In conclusion, tobacco smoking and heavy alcohol consumption are associated with increased risk of HCC, especially when these 2 exposures occur together.

Risk factors for prostate cancer: a case-control study in Greece.

A case-control study of prostate cancer (PC) was undertaken in Athens, Greece. Cases were 320 patients with histologically confirmed incident disease, whereas controls were 246 patients without history or symptomatology of benign prostatic hyperplasia, treated in the same hospitals as the cases for minor diseases or conditions. Cases and controls had similar distributions with respect to height, body mass index, sibship size and birth order in the parental family, marital status and number of offspring in the subject's own family and a long series of previous surgical operations and medical diagnoses, including diabetes mellitus, hepatitis and sexually transmitted diseases. There was also no evidence for a positive association between vertex baldness, tobacco smoking and drinking of coffee or alcoholic beverages, on the one hand, and PC, on the other. There was evidence, however, that some aspect of urban life may increase the risk for PC and a suggestion that sexual activity in early adulthood may be inversely associated with this risk.

Diet during pregnancy and the risk of cerebral palsy.

The role of maternal diet in the development of the fetal brain has not been adequately explored. Marine n-3 fatty acids have, however, been proposed to be important for brain development. The present case-control study aimed to investigate the relationship between dietary intake during pregnancy and the occurrence of cerebral palsy (CP) in the offspring. Children with CP (n 109), born between 1984 and 1988 to mothers residing in the Greater Athens area, were identified at any time in 1991 or 1992 through institutions delivering care and rehabilitation. Successful nutritional interviews were conducted with ninety-one of these children. Controls were chosen among the neighbours of the CP cases or were healthy siblings of children with neurological diseases other than CP, seen by the same neurologists as the children with CP. A total of 278 control children were chosen, and 246 of them were included in the nutritional study. Guardians of all children were interviewed in person on the basis of a questionnaire covering obstetric, perinatal socioeconomic and environmental variables. A validated semiquantitative food-frequency questionnaire of 111 food items was used to estimate maternal dietary intake during pregnancy. Statistical analysis was done by modelling the data through logistic regression. Food groups controlling for energy intake were alternatively and simultaneously introduced in a core model containing non-nutritional confounding variables. Consumption of cereals (mostly bread) and fish intake were inversely associated with CP (P < 0.05 and P < 0.09 respectively) whereas consumption of meat was associated with increased risk (P < 0.02). A protective effect of fish consumption and a detrimental effect of meat intake have been suggested on the basis of earlier work and appear to be biologically plausible. If corroborated by other studies, these results could contribute to our understanding of the nutritional influences on fetal brain development.

Olive oil, other seasoning fats, and the risk of colorectal carcinoma.

BACKGROUND: An association between fats and colorectal carcinoma has been suggested, but the epidemiologic evidence by type of dietary fat is far less clear. Colorectal carcinoma rates have been relatively low in Mediterranean countries compared with most other Western countries, but the components of the Mediterranean diet responsible for this favorable pattern are unclear. METHODS: The relationship between various added (seasoning) fats and colorectal carcinoma risk was investigated using data from a case-control study conducted between January 1992 and June 1996 in six Italian areas. Cases were 1953 patients with incident, histologically confirmed colorectal carcinoma (1225 of the colon and 728 of the rectum) admitted to the major teaching and general hospitals in the study areas. Controls were 4154 subjects with no history of cancer who were admitted to hospitals in the same catchment areas for acute, nonneoplastic diseases unrelated to the the digestive tract and requiring no long term modifications of diet. Dietary habits were investigated using a validated food frequency questionnaire including 78 items. Lipid intake was estimated by taking into account the content of seasoning lipids in different dishes, the frequency of consumption and portion size of each dish, and individual fat intake patterns. RESULTS: The odds ratios (OR) for successive tertiles of olive oil intake, compared with the lowest one, were 0.87 (95% confidence interval [CI], 0.75-1.01) and 0.83 (95% CI, 0.70-0.99) (chi2trend = 4.49, P = 0.03) when colorectal carcinoma was analyzed as a whole, 0.82 (95% CI, 0.68-0.98) and 0.81 (95% CI, 0.66-0.99) (chi2trend = 4.05, P = 0.04) for colon carcinoma, and 0.96 (95% CI, 0.77-1.19) and 0.88 (95% CI, 0.66-1.12) for rectal carcinoma. For specific seed oils (including sunflower, maize, peanut, and soya), the OR for colorectal carcinoma was 0.91 in the highest tertile of intake, and the corresponding values were 1.01 for mixed seed oils and 0.93 for butter. None of these estimates was significantly different from the unity. Allowance for vegetable intake attenuated the apparent protection from olive oil consumption (OR, 0.94 for colon and 0.97 for rectum for the highest tertile), which still was apparent in younger subjects (OR, 0.82 for colon and 0.69 for rectum). CONCLUSIONS: In this study, seasoning fats did not appear to increase the risk of colorectal carcinoma, and there was little evidence for a differential effect by fat type. If such a differential effect exists, it is minor and could favor olive oil.

Energy intake and monounsaturated fat in relation to bone mineral density among women and men in Greece.

BACKGROUND: Several variables have been established as risk factors for osteoporosis: it is more common among women and the gender difference increases with age and with years since menopause. Estrogens, androgens, physical activity, and body mass index have been previously shown to be positively associated with bone mineral density and inversely with risk for fractures. METHODS: To assess the effect on bone mineral content of energy-generating nutrients, healthy men (n = 36) and women (n = 118) ages 25-69 years were interviewed among visitors and staff of the University of Athens Department of Medical Physics. Bone mineral density (BMD) was measured by single photon absorptiometry. RESULTS: Demographic and lifestyle variables were not significantly related to BMD in this study, although the patterns were consistent with those previously reported by other investigators. Total energy intake, which also reflects energy expenditure through physical activity, was positively associated with BMD among both men (P = 0.003) and women (P = 0.04). After adjustment for nonnutritional variables and energy intake, monounsaturated fat, which in the Greek population is mostly derived from olive oil, was associated with BMD. The association was positive among both men (P = 0.01) and women (P = 0.03). There was evidence for an inverse association between carbohydrate intake and BMD, but the association was significant only with respect to mono- and disaccharides. CONCLUSIONS: In this population, consumption of monounsaturated fat and physical activity were predictive of bone mineral density, but larger studies are needed.

Olive oil and human cancer: an assessment of the evidence.

BACKGROUND: We have attempted to summarize the evidence concerning the association of olive oil intake with cancer risk in humans. METHODS: We reviewed all the studies that met the following criteria: (1) they have directly examined olive oil in the context of an extensive food frequency questionnaire or have evaluated the role of monounsaturated fat in populations of Mediterranean countries where a large fraction of monounsaturated fat originates from olive oil and (2) they have analyzed the data with explicit or implicit control for energy intake to accommodate the likely confounding influence of caloric consumption and to account to a certain extent for differential completeness of reporting between cases and controls. Ecologic studies were also considered and relevant experimental data were invoked. RESULTS: With respect to breast cancer, there is converging evidence for a protective effect, although the data are not definitive. For other cancer types, the overall epidemiologic evidence, although promising, is quantitatively limited and qualitatively suboptimal. CONCLUSIONS: The issue is of major public health importance and deserves additional study.

Reliability of information on cigarette smoking and beverage consumption provided by hospital controls.

We compared data from interviews of patients admitted to hospital and interviews repeated at home for 400 hospital controls. Of these, 294 (73.5%) could be re-interviewed (responders). Never smoking was reported by 44% of subjects in the in-hospital interviews and by 40% in the repeat at-home interviews. Among those interviewed in hospital, 38% claimed to be nondrinkers, as did 38% of responders, but only 28% characterized themselves as nondrinkers in the repeat interview. For consumption of regular coffee, 15% reported none in the selected sample, 14% among responders, but only 6% in the repeat at-home interview. Agreement was good for decaffeinated coffee and tea consumption.

A prospective study of alcohol, smoking, caffeine, and the risk of symptomatic diverticular disease in men.

The relationship between smoking, caffeine, and alcohol intake and the risk of symptomatic diverticular disease has not been investigated directly. We examined these associations in a prospective cohort of 47,678 US men, 40 to 75 years old. During 4 years of follow-up (1988 to 1992), we documented 382 newly diagnosed cases of symptomatic diverticular disease. After adjustments for age, physical activity, and energy-adjusted intake of dietary fiber and total fat, alcohol intake (comparing those who drink > 30 g of alcohol/d to nondrinkers) was only weakly and nonsignificantly associated with risk of symptomatic diverticular disease (relative risk (RR) = 1.36; 95 percent confidence interval (CI), 0.94 to 1.97; P for trend = 0.37). We observed no association between caffeine, specific caffeinated beverages, and decaffeinated coffee and the risk of symptomatic diverticular disease. Current smoking was not appreciably associated with risk of symptomatic diverticular disease compared to nonsmokers (RR = 1.25; 95 percent CI, 0.75 to 2.09) after adjustment for age, physical activity, and energy-adjusted intake of dietary fiber and total fat. In a subset analysis restricted to men who had undergone sigmoidoscopy or colonoscopy, a modest positive association was seen between smoking and risk of symptomatic diverticular disease. These results suggest that smoking, caffeine, and alcohol intake are not associated with any substantially increased risk of symptomatic diverticular disease.

A prospective study of diet and adult-onset asthma.

A role for diet in the pathophysiology of asthma may be mediated by altered immune or antioxidant activity with consequent effects on airway inflammation. We evaluated associations between several dietary factors assessed by a semiquantitative food frequency questionnaire, and incidence of asthma over a 10-yr period in 77,866 women 34 to 68 yr of age. Women in the highest quintile of vitamin E intake from diet, but not from supplements, had a risk of 0.53 (95% confidence interval [CI] = 0.33 to 0.86) compared with women in the lowest quintile. This relationship, however, was attenuated when the contribution from nuts, a major source of vitamin E in these data and a possible allergen, was removed (relative risk = 0.74 [0.50 to 1.10], p for trend = 0.007). Positive associations were found for vitamins C and E from supplements, but appeared to be explained by women at high risk of asthma initiating use of vitamin supplements prior to diagnosis. A nonsignificant inverse association with carotene intake was noted, but no clear relations with asthma were demonstrated for intake of linoleic acid or omega-3 fatty acids. These data suggest that antioxidant supplementation and intake of various fats during adulthood are not important determinants of asthma, although vitamin E from diet may have a modest protective effect.

Coffee intake and other factors in relation to multiple deliveries: a study in Greece.

We conducted a case-control study of factors that may be related to the prevalence of multiple births with at least one liveborn. Over a period of 15 months during 1991-1992 in Athens, Greece, we identified 380 women who had a multiple birth that was delivered in one of the six larger maternity hospitals in the area. We selected as controls 380 livebirth singleton pregnancies delivered at the same hospitals immediately following a multiple pregnancy. All mothers were interviewed in the maternity wards or at home, and zygosity was ascertained through the similarity method. The odds ratio for ovulation-inducing drugs was not elevated for monozygotic twins, but it was 9-fold for dizygotic twins and 90-fold for triplets or quadruplets. We excluded drug-induced pregnancies, twins of indeterminable zygosity, and all triplets from further analyses. We found no remarkable association between any of the study variables and the occurrence of monozygotic twins, with the exception of an increasing trend with age. For dizygotic twins, we found weak associations in the expected directions with maternal age (positive) and height (positive) as well as with parity and number of induced abortions (positive). A history of oral contraceptive use was inversely, but weakly, associated with dizygotic twinning. Each cup of coffee per day was associated with an increment in the odds ratio of 1.23-fold. (95% confidence interval = 1.05-1.43). Restriction of the analysis to dizygotic twins of different gender increased the point estimate of the odds ratio to 1.31 for each cup of coffee consumed daily.(ABSTRACT TRUNCATED AT 250 WORDS)

Consumption of olive oil and specific food groups in relation to breast cancer risk in Greece.

BACKGROUND: Experimental animal studies suggest that olive oil consumption, as contrasted to consumption of other fat types, does not enhance the occurrence of chemically induced mammary tumors, but human data are sparse. Furthermore, evidence is inconclusive concerning the role of food groups, as distinct from that of major nutrients, in the etiology of breast cancer in women. PURPOSE: This analysis was conducted to evaluate and quantify the effect of consumption of olive oil, margarine, and a range of food groups on the risk of breast cancer. METHODS: Data from a comprehensive, semiquantitative food-frequency questionnaire administered to 820 women with breast cancer and 1548 control women from the study base were used to calculate odds ratios (ORs) and X statistics of linear trend for the consumption of olive oil, margarine, and a series of food groups classified in quintiles. Adjustment for the effects of reproductive risk factors, energy intake, and mutual confounding influences was implemented through unconditional logistic regression modeling. RESULTS: Vegetable consumption and fruit consumption were independently associated with statistically significant reductions of breast cancer risk by 12% and 8%, respectively, per quintile increase; no significant associations were evident for the other food groups examined. Increased olive oil consumption was associated with significantly reduced breast cancer risk (OR = 0.75 [95% confidence interval = 0.57-0.98] for more than once a day versus once a day), whereas increased margarine consumption was associated with significantly increased risk (OR = 1.05 [95% confidence interval = 1.00-1.10] for an increment of four times a month). The olive oil association was apparently concentrated among postmenopausal women, but the relevant interaction term was not statistically significant; there was no suggestion of interaction with menopausal status for consumption of either vegetables, fruits, or margarine. CONCLUSIONS: Although major categories of macronutrients do not show significant associations with breast cancer risk in most studies, including the present one, vegetables and fruits are inversely, significantly, and strongly associated with this risk. There also is evidence that olive oil consumption may reduce the risk of breast cancer, whereas margarine intake appears to be associated with an elevated risk for the disease.

The association of fat and other macronutrients with breast cancer: a case-control study from Greece.

The Greek diet is characterized by a high total fat but low saturated fat intake. In a hospital-based case-control study of female breast cancer conducted in Athens (1989-91), 820 patients with confirmed cancer of the breast were compared with 795 orthopaedic patient controls and 753 hospital visitor controls, matched to the cases by age and interviewer. Diet was ascertained through a semiquantitative food frequency questionnaire; macronutrient intakes were estimated from the nutrient content of a selected typical portion size for each specified food item, summed for all items. Logistic regression was used to analyse the data, controlling for demographic and reproductive risk factors for breast cancer as well as for total energy intake and mutual confounding influences among nutrients. There was no significant or suggestive association of total protein, total fat, categories of fat or total carbohydrates with breast cancer risk. Thus, the mutually adjusted relative risk per quintile and (in parenthesis) 95% confidence interval were: for protein, 1.06 (0.94-1.20); saturated fat, 0.99 (0.89-1.11); monounsaturated fat, 0.97 (0.88-1.07), polyunsaturated fat, 1.05 (0.97-1.13); and total carbohydrates, 1.03 (0.94-1.12). In alternative analytical approaches only total protein appeared to be positively associated to the occurrence of breast cancer with some consistency, but the results were far from statistically significant. These findings do not support a role for fat or other energy-generating nutrients in the aetiology of breast cancer.