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Background:Ovarian cancer has a high case-fatality ratio, largely due to late diagnosis. Epidemiologic risk prediction models could help identify women at increased risk who may benefit from targeted prevention measures, such as screening or chemopreventive agents.Methods:We built an ovarian cancer risk prediction model with epidemiologic risk factors from 202 206 women in the European Prospective Investigation into Cancer and Nutrition study.Results:Older age at menopause, longer duration of hormone replacement therapy, and higher body mass index were included as increasing ovarian cancer risk, whereas unilateral ovariectomy, longer duration of oral contraceptive use, and higher number of full-term pregnancies were decreasing risk. The discriminatory power (overall concordance index) of this model, as examined with five-fold cross-validation, was 0.64 (95% confidence interval (CI): 0.57, 0.70). The ratio of the expected to observed number of ovarian cancer cases occurring in the first 5 years of follow-up was 0.90 (293 out of 324, 95% CI: 0.81-1.01), in general there was no evidence for miscalibration.Conclusion:Our ovarian cancer risk model containing only epidemiological data showed modest discriminatory power for a Western European population. Future studies should consider adding informative biomarkers to possibly improve the predictive ability of the model. [ABSTRACT FROM AUTHOR]

Background:Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations.Methods:In 486 799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d−1 increments of vegetable/fruit intakes.Results:Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d−1 increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d−1 increment): 1.01; 95% CI: 0.92-1.11.Conclusions:Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease. [ABSTRACT FROM AUTHOR]

Background:Prospective studies on insulin-like growth factor I (IGF-I) and epithelial ovarian cancer (EOC) risk are inconclusive. Data suggest risk associations vary by tumour characteristics.Methods:We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate IGF-I concentrations and EOC risk by tumour characteristics (n=565 cases). Multivariable conditional logistic regression models were used to estimate associations.Results:We observed no association between IGF-I and EOC overall or by tumour characteristics.Conclusions:In the largest prospective study to date was no association between IGF-I and EOC risk. Pre-diagnostic serum IGF-I concentrations may not influence EOC risk. [ABSTRACT FROM AUTHOR]

Background:There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Methods:A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases.Results:During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62-0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC.Conclusions:Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The role of diet in the prevention of diabetes remains uncertain. The aim of this study was to investigate two different dietary aspects, i.e. adherence to the Mediterranean diet and glycaemic load (GL), in relation to diabetes occurrence. Methods: We analysed data from the Greek cohort of the population-based European Prospective Investigation into Cancer and Nutrition (EPIC). From a total of 22,295 participants, actively followed for a median of 11.34 years, 2,330 cases of incident type 2 diabetes were recorded. All participants completed a validated, interviewer-administered semi-quantitative food frequency questionnaire at enrolment. From this information, we calculated a ten point Mediterranean diet score (MDS), reflecting adherence to the traditional Mediterranean diet, as well as the dietary GL. We estimated HRs and the corresponding 95% CIs of diabetes using Cox proportional hazards regression models adjusted for potential confounders. Results: A higher MDS was inversely associated with diabetes risk (HR 0.88 [95% CI 0.78, 0.99] for MDS ≥6 vs MDS ≤3). GL was positively associated with diabetes (HR 1.21 [95% CI 1.05, 1.40] for the highest vs the lowest GL quartile). A significant protection of about 20% was found for a diet with a high MDS and a low GL. Conclusions/interpretation: A low GL diet that also adequately adheres to the principles of the traditional Mediterranean diet may reduce the incidence of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background:Smoking is not associated with prostate cancer incidence in most studies, but associations between smoking and fatal prostate cancer have been reported.Methods:During 1992 and 2000, lifestyle information was assessed via questionnaires and personal interview in a cohort of 145 112 European men. Until 2009, 4623 incident cases of prostate cancer were identified, including 1517 cases of low-grade, 396 cases of high grade, 1516 cases of localised, 808 cases of advanced disease, and 432 fatal cases. Multivariable Cox proportional hazards regression models were used to examine the association of smoking status, smoking intensity, and smoking duration with the risk of incident and fatal prostate cancer.Results:Compared with never smokers, current smokers had a reduced risk of prostate cancer (RR=0.90, 95% CI: 0.83-0.97), which was statistically significant for localised and low-grade disease, but not for advanced or high-grade disease. In contrast, heavy smokers (25+ cigarettes per day) and men who had smoked for a long time (40+ years) had a higher risk of prostate cancer death (RR=1.81, 95% CI: 1.11-2.93; RR=1.38, 95% CI: 1.01-1.87, respectively).Conclusion:The observation of an increased prostate cancer mortality among heavy smokers confirms the results of previous prospective studies. [ABSTRACT FROM AUTHOR]

Background:Limited information exists about the endocrine milieu of benign breast disease (BBD), a documented breast cancer risk factor. We compared blood levels of estrogens, testosterone and insulin-like growth factor-1 (IGF-1) between BBD patients by histological type and women without breast pathology.Methods:We studied 578 BBD patients and 178 healthy women in Athens, Greece, who provided blood samples, and completed interviewer-administered questionnaires.Results:Of the BBD patients, 254 had non-proliferative disease, 268 proliferative disease without atypia and 56 atypical hyperplasia. Comparing BBD patients with healthy women, the per cent differences (and 95% confidence intervals) for blood hormones, among pre-menopausal and peri/post-menopausal women, respectively, were: 22.4% (−4.0%, 56.1%) and 32.0% (5.6%, 65.1%) for estradiol; 26.2% (10.1%, 44.8%) and 30.9% (16.8%, 46.6%) for estrone; 19.5% (3.1%, 38.4%) and 16.5% (−5.0%, 42.9%) for testosterone; and −5.2% (−13.8%, 4.4%) and −12.1% (−19.8%, −3.6%) for IGF-1. Steroid hormones tended to be higher in proliferative compared with non-proliferative BBD.Conclusions:Circulating steroid hormones tend to be higher among women with BBD than women with no breast pathology and higher in proliferative than non-proliferative disease; these patterns are more evident among peri/post-menopausal women. In peri/post-menopausal women IGF-1 was lower among women with BBD compared with healthy women. [ABSTRACT FROM AUTHOR]

Background/objectives:Heavy alcohol drinking is a risk factor of colorectal cancer (CRC), but little is known on the effect of polymorphisms in the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) on the alcohol-related risk of CRC in Caucasian populations.Subjects/methods:A nested case-control study (1269 cases matched to 2107controls by sex, age, study centre and date of blood collection) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the impact of rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms on CRC risk. Using the wild-type variant of each polymorphism as reference category, CRC risk estimates were calculated using conditional logistic regression, with adjustment for matching factors.Results:Individuals carrying one copy of the rs1229984(A) (ADH1B) allele (fast metabolizers) showed an average daily alcohol intake of 4.3 g per day lower than subjects with two copies of the rs1229984(G) allele (slow metabolizers) (Pdiff<0.01). None of the polymorphisms was associated with risk of CRC or cancers of the colon or rectum. Heavy alcohol intake was more strongly associated with CRC risk among carriers of the rs1573496(C) allele, with odds ratio equal to 2.13 (95% confidence interval: 1.26-3.59) compared with wild-type subjects with low alcohol consumption (Pinteraction=0.07).Conclusions:The rs1229984(A) (ADH1B) allele was associated with a reduction in alcohol consumption. The rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms were not associated with CRC risk overall in Western-European populations. However, the relationship between alcohol and CRC risk might be modulated by the rs1573496 (ADH7) polymorphism. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: There has been long-standing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development. Prospective epidemiological studies have shown variable relationships between pancreatic cancer risk and blood markers of glucose and insulin metabolism, overall and as a function of lag times between marker measurements (blood donation) and date of tumour diagnosis. Methods: Pre-diagnostic levels of HbA and C-peptide were measured for 466 participants with pancreatic cancer and 466 individually matched controls within the European Prospective Investigation into Cancer and Nutrition. Conditional logistic regression models were used to estimate ORs for pancreatic cancer. Results: Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA levels up to an OR of 2.42 (95% CI 1.33, 4.39 highest [≥6.5%, 48 mmol/mol] vs lowest [≤5.4%, 36 mmol/mol] category), even for individuals with HbA levels within the non-diabetic range. C-peptide levels showed no significant relationship with pancreatic cancer risk, irrespective of fasting status. Analyses showed no clear trends towards increasing hyperglycaemia (as marked by HbA levels) or reduced pancreatic beta cell responsiveness (as marked by C-peptide levels) with decreasing time intervals from blood donation to cancer diagnosis. Conclusions/interpretation: Our data on HbA show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in HbA levels, relatively independently of obesity and insulin resistance-the classic and major risk factors for type 2 diabetes. While there is no strong difference by lag time, more data are needed on this in order to reach a firm conclusion. [ABSTRACT FROM AUTHOR]

Background: Although several studies have investigated the association of the Mediterranean diet with overall mortality or risk of specific cancers, data on overall cancer risk are sparse.Methods: We examined the association between adherence to Mediterranean dietary pattern and overall cancer risk using data from the European Prospective Investigation Into Cancer and nutrition, a multi-centre prospective cohort study including 142,605 men and 335,873. Adherence to Mediterranean diet was examined using a score (range: 0-9) considering the combined intake of fruits and nuts, vegetables, legumes, cereals, lipids, fish, dairy products, meat products, and alcohol. Association with cancer incidence was assessed through Cox regression modelling, controlling for potential confounders.Results: In all, 9669 incident cancers in men and 21,062 in women were identified. A lower overall cancer risk was found among individuals with greater adherence to Mediterranean diet (hazard ratio=0.96, 95% CI 0.95-0.98) for a two-point increment of the Mediterranean diet score. The apparent inverse association was stronger for smoking-related cancers than for cancers not known to be related to tobacco (P (heterogeneity)=0.008). In all, 4.7% of cancers among men and 2.4% in women would be avoided in this population if study subjects had a greater adherence to Mediterranean dietary pattern.Conclusion: Greater adherence to a Mediterranean dietary pattern could reduce overall cancer risk. [ABSTRACT FROM AUTHOR]

Breast cancer incidence and birth weight are higher among Caucasian than Asian women, and birth size has been positively associated with breast cancer risk. Pregnancy hormone levels, however, have been generally lower in Caucasian than Asian women. We studied components of the insulin-like growth factor (IGF) system in cord blood from 92 singleton babies born in Boston, USA, and 110 born in Shanghai, China, in 1994-1995. Cord blood IGF-1 was significantly higher among Caucasian compared with Chinese babies (P<10(-6)). The opposite was noted for IGF-2 (P approximately 10(-4)). IGF-1 was significantly positively associated with birth weight and birth length in Boston, but not Shanghai. In contrast, stronger positive, though statistically non-significant, associations of IGF-2 with birth size were only evident in Shanghai. The associations of birth weight and birth length were positive and significant in taller women (for IGF-1 in Boston P approximately 0.003 and 0.03, respectively; for IGF-2 in Shanghai P approximately 0.05 and approximately 0.04, respectively), among whom maternal anthropometry does not exercise strong constraints in foetal growth. The documentation of higher cord blood levels of IGF-1, a principal growth hormone that does not cross the placenta, among Caucasian than in Asian newborns is concordant with breast cancer incidence in these populations. [ABSTRACT FROM AUTHOR]

Birth size of a woman has been positively associated with her breast cancer risk, particularly before menopause, but no study has investigated neonatal growth in relation to this risk. We conducted a case–control study nested within a population-based cohort of women, born in Sweden between 1901 and 1961, covering all 405 breast cancer patients and 1081 age- and hospital-matched controls, who were born after newborn charts became available. Compared to neonates who lost <200 g after birth and grew at a rate <25 g day−1 after reaching postnatal weight nadir (ie, the minimum, before starting to regain weight), those who either lost 200 g after birth or grew 25 g day−1 after nadir, or both, were at an approximately 50% increased breast cancer risk. The excess risk was striking and statistically significant among women below 50 years of age, but was not evident among older women. Immediate postnatal weight loss (an indicator of water loss, likely to reflect water retention associated with pregnancy hormones) as well as neonatal weight gain rate after the nadir (known to reflect growth hormone levels) was significantly positively associated with premenopausal breast cancer risk.British Journal of Cancer (2008) 99, 1544–1548. doi:10.1038/sj.bjc.6604702 www.bjcancer.com Published online 30 September 2008 [ABSTRACT FROM AUTHOR]

Adherence to traditional Mediterranean diet (MD) has been reported to be inversely associated with total, as well as cardiovascular, mortality. We have examined the relation between degree of such adherence and incidence of cancer overall in a general population sample of 25 623 participants (10 582 men, 15 041 women) of the Greek segment of the European Prospective Investigation into Cancer and nutrition (EPIC). All subjects completed a validated, interviewer-administered, semi-quantitative food-frequency questionnaire at enrolment. Degree of adherence to the traditional MD was assessed through a 10-point scale (0 minimal; 9 maximal) that incorporated key dietary characteristics. During a median follow-up of 7.9 years and 188 042 total person-years, 851 medically confirmed incident cancer cases (421 men, 430 women) were recorded. Using proportional hazards regression with adjustment for potential confounders, we found that a higher degree of MD adherence was associated with lower overall cancer incidence. A two-point increase in the score corresponded to a 12% reduction in cancer incidence (adjusted hazard ratio, 0.88 (95% confidence interval 0.80, 0.95)). The association was exposure-dependent and stronger among women. This inverse association with MD adherence was considerably stronger than that predicted on the basis of the associations of the individual components of this diet and points to the value of analysing dietary patterns in cancer studies. [ABSTRACT FROM AUTHOR]

We examined the relation with birth weight and umbilical cord blood concentrations of haematopoietic stem and progenitor populations in 288 singleton infants. Across the whole range of birth weight, there was a positive relation between birth weight and CD34+CD38(-) cells, with each 500 g increase in birth weight being associated with a 15.5% higher (95% confidence interval: 1.6-31.3%) cell concentration. CD34+ and CD34+c-kit+ cells had J-shaped relations and CFU-GM cells had a U-shaped relation with birth weight. Among newborns with >or=3000 g birth weights, concentrations of these cells increased with birth weight, while those below 3000 g had higher stem cell concentrations than the reference category of 3000-3499 g. Adjustment for cord blood plasma insulin-like growth factor-1 levels weakened the stem and progenitor cell-birth weight associations. The positive associations between birth weight and stem cell measurements for term newborns with a normal-to-high birth weight support the stem cell burden hypothesis of cancer risk. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective:The aim of this study was to examine the relationship of diet with serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in women.Design:Cross-sectional study.Setting and subjects:The population are 2109 women who were control subjects in a case–control study of breast cancer nested in the European Prospective Investigation into Cancer and Nutrition. Control subjects were randomly chosen among risk sets consisting of female cohort members alive and free of cancer (except non-melanoma skin cancer) at the time of diagnosis of the index case. Matching criteria were age at enrolment, follow-up time, time of the day of blood collection and study centre. Diet was measured through validated questionnaires. Serum hormone concentrations were measured by enzyme-linked immunosorbent assays. The relationship between serum IGF-I, IGFBP-3, and intake of nutrients and foods was explored by linear regression in models adjusted for energy intake, age, body mass index, smoking, physical activity, centre and laboratory batch.Results:Serum IGF-I levels were positively related to protein intake (P trend<0.001), but not related to energy, fat or carbohydrate intake. Positive relationships were observed with the intake of milk (P trend=0.007), calcium (P trend<0.001), magnesium (P trend=0.003), phosphorus (P trend<0.001), potassium (P trend=0.002), vitamin B6 (P trend=0.03), vitamin B2 (P trend=0.001) and inverse relationships with vegetables (P trend=0.02) and beta-carotene (P trend=0.02). IGFBP-3 was not related with most of the nutrients and foods in this study.Conclusions:In this population, circulating IGF-I is modestly related with the intake of protein and minerals, and with milk and cheese, while IGFBP-3 does not appear to be related with diet.European Journal of Clinical Nutrition (2007) 61, 91–98. doi:10.1038/sj.ejcn.1602494; published online 9 August 2006 [ABSTRACT FROM AUTHOR]

Objective:To explore the independent associations of body height, body mass index (BMI), waist circumference and hip circumference with high-density lipoprotein-cholesterol (HDL-cholesterol) and non-high-density lipoprotein-cholesterol (non-HDL-cholesterol), in a large general population sample.Design:Cross sectional.Setting:Urban and rural areas throughout Greece.Subjects:In total,10 837 volunteers, 2034 men and 8803 women, aged 25–82 years, participants in the European Prospective Investigation into Cancer and Nutrition study (EPIC), who have never smoked and never been treated for dyslipidemia.Interventions:None.Results:The effect of height on non-HDL-cholesterol was opposite but in absolute terms almost as important as that of BMI with no gender interaction. Among women, hip circumference was inversely associated with non-HDL-cholesterol (standardized coefficient b st=−1.11, with standard error (s.e.)=0.42) and positively with HDL-cholesterol (b st=0.85, s.e.=0.12) whereas, waist circumference was inversely associated with HDL-cholesterol (b st=−1.16, s.e.=0.13) and strongly positively with non-HDL-cholesterol (b st=8.83, s.e.=0.45). Among men, associations were generally weaker (in absolute terms by about 50%) and for hip circumference the association with non-HDL-cholesterol was actually non significantly positive.Conclusions:Height was inversely associated with HDL and non-HDL-cholesterol implicating early life phenomena in the regulation of these variables. Larger hip circumference among women had beneficial effects on blood cholesterol fractions by increasing HDL-cholesterol and reducing non-HDL-cholesterol, whereas among men the relevant effects were less clear cut. The detrimental consequences of large waist circumference on both HDL (reduction) and non-HDL-cholesterol (increase) were also particularly marked among women.Sponsorship:The European Prospective Investigation into Cancer and Nutrition (EPIC) is coordinated by the International Agency for Research on Cancer (World Health Organization) and supported by the Europe Against Cancer Program of the European Commission. The Greek segment of the EPIC study is also supported by the Greek Ministry of Health and the Greek Ministry of Education. This study was additionally supported by the fellowship ‘Vassilios and Nafsika Tricha’.European Journal of Clinical Nutrition (2006) 60, 942–948. doi:10.1038/sj.ejcn.1602403; published online 8 February 2006 [ABSTRACT FROM AUTHOR]

Objective: To assess the relation between specific flavonoid classes and peripheral arterial occlusive disease (PAOD), an important manifestation of atherosclerosis.Design: Using data from a case-control study conducted in Greece in 1980 on the nutritional epidemiology of PAOD, we have exploited recently published databases on the content of foods in specific flavonoid classes to assess the relation between intake of these compounds and PAOD.Setting: A major teaching hospital in Athens, Greece.Subjects: Cases were 100 patients with PAOD and controls 100 patients with minor surgical conditions admitted to the same hospital.Interventions: No interventions. All cases and controls were interviewed in the hospital wards, and a 110-food item semiquantitative food frequency questionnaire was administered by the same interviewer.Results: Flavonols, flavones and perhaps flavan-3-ols were inversely associated with PAOD risk, the odds ratios (and 95% confidence intervals) for increments equal to the corresponding standard deviations being 0.41 (0.20-0.86), 0.56 (0.32-0.96) and 0.53 (0.26-1.05), respectively. Total flavonoids were also significantly inversely associated with PAOD.Conclusions: On the basis of these results, the biological properties of flavonoids and evidence concerning their relation to other manifestations of atherosclerosis, we conclude that dietary intake of specific classes of flavonoids, as well as total flavonoids, may have a protective effect against PAOD.Sponsorship: This study was partially supported by a grant to Harvard University by the Samourkas Foundation. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor I (IGF-I) stimulates cell proliferation and can enhance the development of tumours in different organs. Epidemiological studies have shown that an elevated level of circulating IGF-I is associated with increased risk of breast cancer, as well as of other cancers. Most of circulating IGF-I is bound to an acid-labile subunit and to one of six insulin-like growth factor binding proteins (IGFBPs), among which the most important are IGFBP-3 and IGFBP-1. Polymorphisms of the IGF1 gene and of genes encoding for the major IGF-I carriers may predict circulating levels of IGF-I and have an impact on cancer risk. We tested this hypothesis with a case-control study of 807 breast cancer patients and 1588 matched control subjects, nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 23 common single nucleotide polymorphisms in IGF1, IGFBP1, IGFBP3 and IGFALS, and measured serum levels of IGF-I and IGFBP-3 in samples of cases and controls. We found a weak but significant association of polymorphisms at the 5' end of the IGF1 gene with breast cancer risk, particularly among women younger than 55 years, and a strong association of polymorphisms located in the 5' end of IGFBP3 with circulating levels of IGFBP-3, which confirms previous findings. Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians. [ABSTRACT FROM AUTHOR]

Adiponectin, an adipocyte-specific secretory protein known to induce apoptosis, has been reported to be inversely related to breast and endometrial cancers and recently found to inhibit proliferation of myeloid but not lymphoid cell lines. We hypothesised that adiponectin may be inversely associated with acute myeloblastic leukaemia (AML), but not with acute lymphoblastic leukaemia of B (ALL-B) or T (ALL-T) cell origin in children. Blood samples and clinical information were collected over the period 1996-2000 from 201 children (0-14 years old) with leukaemia (22 AML, 161 ALL-B and 18 ALL-T cases) through a national network of childhood Hematology-Oncology units in Greece and from 201 controls hospitalised for minor pediatric ailments. Serum adiponectin levels were measured under code, at the Beth Israel Deaconess Medical Center, Boston, MA, USA using a radioimmunoassay procedure. Each of the three leukaemia groups was compared with the control group through multiple logistic regression. Odds ratios (OR) and 95% confidence intervals (95% CI) for an increase of adiponectin equal to 1 s.d. among controls were estimated controlling for gender, age, as well as for height and weight, expressed in age-gender-specific centiles of Greek growth curves. Adiponectin was inversely associated with AML (OR=0.56; 95% CI, 0.34-0.94), whereas it was not significantly associated with either ALL-B (OR=0.88; 95% CI, 0.71-1.10) or ALL-T (OR=1.08; 95% CI, 0.67-1.72). Biological plausibility and empirical evidence point to the importance of this hormone in the pathogenesis of childhood AML. [ABSTRACT FROM AUTHOR]

We examined prospectively the association between weight change during adulthood and breast cancer risk, using data on 1358 incident cases that developed during 5.8 years of follow-up among 40,429 premenopausal and 57,923 postmenopausal women from six European countries, taking part in the European prospective investigation into cancer and nutrition study. Multivariate Cox regression models were used to calculate hazard ratios according to weight change (kg), defined as the weight difference between age at enrollment and age 20 adjusted for other risk factors. Changes in weight were not associated with premenopausal breast cancer risk. In postmenopausal women, weight gain was positively associated with breast cancer risk only among noncurrent hormone replacement therapy (HRT) users (P-trend < or = 0.0002). Compared to women with a stable weight (+/-2 kg), the relative risk for women who gained 15-20 kg was 1.50 (95% confidence interval (CI) 1.06-2.13). The pooled RR per weight gain increment of 5 kg was 1.08 (95% CI 1.04-1.12). Weight gain was not associated with breast cancer risk in current HRT users, although, overall, these women experienced a much higher risk of breast cancer compared with nonusers. Our findings suggest that large adult weight gain was a significant predictor of breast cancer in postmenopausal women not taking exogenous hormones. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: Maternal weight gain has been consistently linked to birth weight but, beyond maternal energy intake, no macronutrient has been associated with either of them. We have examined whether maternal energy-adjusted intake of macronutrients is associated with either maternal weight gain or birth-size parameters. DESIGN:: Cohort study. SETTING:: University hospital in Boston, USA. SUBJECTS:: A total of 224 pregnant women coming for their first routine prenatal visit. The women were followed through delivery. INTERVENTIONS:: None. Pregnant women's dietary intake during the second trimester was ascertained at the 27th week of pregnancy through a food frequency questionnaire. RESULTS:: Intake of neither energy nor any of the energy-generating nutrients was significantly associated with birth size. In contrast, maternal weight gain by the end of the second trimester of pregnancy was significantly associated with energy intake (+0.9?kg/s.d. of intake; P~0.006) as well as energy-adjusted intake of protein (+3.1?kg/s.d. of intake; P<10-4), lipids of animal origin (+2.6?kg/s.d. of intake; P<10-4) and carbohydrates (-5.2?kg/s.d. of intake; P<10-4). CONCLUSIONS:: Although maternal weight gain is strongly associated with birth size, the indicated nutritional associations with weight gain are not reflected in similar associations with birth-size parameters. The pattern is reminiscent of the sequence linking diet to coronary heart disease (CHD) through cholesterol: diet has been conclusively linked to blood cholesterol levels and cholesterol levels are conclusively linked to this disease, even though the association of diet with CHD has been inconclusive and controversial. SPONSORSHIP:: This study was supported in part by Grant No. CA54220 from the National Institutes of HealthEuropean Journal of Clinical Nutrition (2004) 58, 231-237. doi:10.1038/sj.ejcn.1601771 [ABSTRACT FROM AUTHOR]

OBJECTIVE:: To identify dietary patterns, and their socio-demographic and lifestyle correlates in a large sample of Greek adults, and assess their adherence to the traditional Mediterranean diet. DESIGN:: Principal component (PC) analysis was used to identify dietary patterns among 28 034 participants of the Greek branch of the European Prospective Investigation into Cancer and Nutrition. Dietary information was collected through a validated, semiquantitative, food-frequency questionnaire. The extracted PCs were subsequently regressed on sociodemographic and lifestyle variables. Analyses were also performed to classify individuals with similar dietary behavior into clusters. RESULTS:: Four PCs were identified: PC1 resembled the Mediterranean diet, PC2 approximated a vegetarian diet with emphasis on seed oils, PC3 reflected a preference for sweets, and PC4 reflected a Western diet. PC1 and PC2 were positively associated with age, education, physical activity, and nonsmoking status. Females, in comparison to males, scored higher on PC1 but lower on PC2. Males, younger, more educated individuals, nonsmokers and residents of Greater Athens (Attica) scored higher on PC3. PC4 was associated with younger age, less education, and current smoking. In cluster analyses, cluster A contrasted clusters B and C in having much higher mean PC1- and PC2-scores and substantially lower PC3- and PC4-scores. PC1 and PC4 were, respectively, positively and inversely correlated with an a priori Mediterranean-diet score; PC2 and PC3 were unrelated to it. CONCLUSION:: The Mediterranean-like PC1-score as well as the vegetarian-like PC2 were higher among older, more educated people, and were associated with a healthier lifestyle than PC4, which reflected a Western-type diet. PC1 was strongly positively associated with an a priori Mediterranean-diet score. SPONSORSHIP:: The European Prospective Investigation into Cancer and Nutrition (EPIC) is coordinated by the International Agency for Research on Cancer and supported by the Europe Against Cancer Programme of the European Commission. The Greek segment of the EPIC study is also supported by the Greek Ministry of Health and the Greek Ministry of Education.European Journal of Clinical Nutrition (2003) 57, 1378-1385. doi:10.1038/sj.ejcn.1601699 [ABSTRACT FROM AUTHOR]

Flavonoids have been investigated for possible inverse associations with various chronic degenerative diseases, but there are no epidemiologic data concerning a possible association between several of the main flavonoid categories and breast cancer risk. We have applied recently published data on the flavonoid content of several foods and beverages on dietary information collected in the context of a large case-control study of 820 women with breast cancer and 1548 control women, conducted in Greece. We found a strong, statistically significant inverse association of flavone intake with breast cancer. The odds ratio for an increment equal to one standard deviation of daily flavone intake (i.e. 0.5 mg day(-1)) was 0.87, with 95% confidence interval 0.77-0.97. The association persisted after controlling for fruit and vegetable consumption, or for other flavonoid intake. This inverse association is compatible with and may explain the reported inverse association of breast cancer with consumption of vegetables, particularly leafy vegetables. After controlling for dietary confounding, there was no association of breast cancer risk with flavanones, flavan-3-ols, flavonols, anthocyanidins or isoflavones. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Women born after pre-eclamptic pregnancies have been reported to be at reduced risk of breast cancer as adults, because of reduced intrauterine oestrogen influence on breast tissue; high levels of alpha-foetoprotein (a glycoprotein with anti-oestrogenic properties), however, could also be important. In severe pre-eclampsia, placental function and foetal growth are reduced, and umbilical cord plasma levels of alpha-foetoprotein could reflect the underlying processes. Umbilical cord blood was collected in 12804 consecutive deliveries. Among 307 pregnancies with clinical pre-eclampsia, 66 singleton pregnancies were identified as clinically severe, and 610 singleton pregnancies were selected as controls. Oestradiol and alpha-foetoprotein were measured from umbilical plasma, and birth weight was standardized as the ratio between the observed and expected birth weight, adjusted for differences in gestation length and offspring sex. Cord plasma levels of alpha-foetoprotein were significantly higher in severe pre-eclampsia than controls (P<0.01) after adjustment for gestational age and birth weight. For oestradiol, there was no difference in cord plasma levels between the severe pre-eclampsia group and controls, after adjustment for length of gestation and birth weight. These results suggest that an anti-oestrogenic effect associated with pre-eclampsia may be mediated through high levels of alpha-foetoprotein rather than low levels of oestradiol. [ABSTRACT FROM AUTHOR]

Since sports participation entails the risk of injuries that account for substantial morbidity and disability, the existence of adequate epidemiological information is essential for the development of sound preventive strategies. In this study, we present data on the occurrence of sports injuries among children in six European countries, namely Austria, Denmark, France, Greece, The Netherlands, and the United Kingdom. An operational definition for sports injuries was developed, and comparable data from the European Home and Leisure Accident Surveillance System, an established injury surveillance system operating in 12 European union countries, were collected from the participating member states, during a 1-year period (1998). Sports injuries were examined in schools, in organised and unorganised settings, and in specific types of sports by demographics and injury descriptive variables. Sports injuries represent a quantitatively important and sufficiently serious problem in European union countries, accounting for an estimated annual number of about a quarter of a million outpatient visits in two of the participating countries, which provide national estimates. It is evident, that sport injuries are not only common but also injuries of considerable severity, since a large fraction represents fractures, while approximately 4% of the total require hospitalisation. Football and basketball among male children are, in declining order, the two sports responsible for the most frequent injuries in the European union countries, whereas gymnastics and volleyball prevail among females. The study indicates the importance of injury surveillance in describing the epidemiology of sports injuries and provides an estimate of the magnitude and the profile of sport injuries that take place annually in European union countries. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between alcoholism and risk of male breast cancer.Methods: We conducted a retrospective population-based cohort study in Sweden of men diagnosed with alcoholism between 1965 and 1995. The cohort was followed up through interlinkages with nationwide registries (the national cancer registry, immigration registry, causes of death registry, and population registry), using the national registration numbers. Standardized incidence ratios (SIRs), calculated using the Swedish national cancer incidence rate as reference, were used as estimates of relative risks.Results: A total of 145,811 men were enrolled into the cohort, contributing 1,499,504 person-years of follow-up. Sixteen incident breast cancer cases were identified, and the mean age at diagnosis was 68 years. We excluded the first year of follow-up (cases and person-years) from the analysis to avoid detection bias. The overall SIR (excluding the first year of follow-up) was 1.1 (95% CI 0.6-2.0). Although based on small numbers we found no indication of a differential SIR according to duration of follow-up, age at cohort enrolment, or age at follow-up (attained age or age at cancer diagnosis).Conclusion: The observed associations are not compatible with an increase in breast cancer risk among male alcoholics. [ABSTRACT FROM AUTHOR]

Objective: Acute lymphoblastic leukemia (ALL) among children may be a rare outcome of a delayed non-specific infection in situations of overall low herd immunity. We evaluated the hypothesis as to whether newly diagnosed ALL cases, compared to their controls, are characterized by lower herd immunity, as reflected in a more seronegative spectrum to several agents, with the exception of a strongly positive response to a single infectious agent, assumed to trigger ALL.Methods: The study included 94 incident cases of ALL, from all pediatric hematology-oncology units of Greece, and 94, matched for age and gender, controls hospitalized with minor non-infectious conditions. The past exposure to common infections was assessed using 10 serological markers.Results: There was little evidence for an association of ALL with the serology of any of the studied infectious agents among the very young children. In contrast, among children aged 5 years or older, leukemia was inversely associated with seropositivity to Epstein-Barr virus, human herpes virus-6, Mycoplasma pneumoniae and parvovirus B19.Conclusions: Among children aged 5 years or older the risk of leukemia may be higher when the low herd immunity for several agents is challenged by late infection from an agent that, as a rule, would attack children at a younger age. [ABSTRACT FROM AUTHOR]

We studied the relation of certain endocrine-related variables among 23 cases of male breast cancer and 76 apparently healthy male controls. There were significant inverse associations with smoking (P = 0.03), birth order (P = 0.02) and reported frequency of orgasms in later life (P = 0.0004). The study provides strong indirect evidence that endocrine factors are important in the aetiology of male breast cancer. [ABSTRACT FROM AUTHOR]

Objective: Insulin-like growth factor-1 (IGF-1) and its principal binding protein-3 (IGFBP-3) are central in the mediation of the effect of growth hormone, and the IGF system has been reported to play a role in the pathogenesis of childhood leukemia.Methods: To further evaluate the hypothesis connecting the IGF system to this disease, we have examined whether IGF-1 and IGFBP-3 are associated with the two main endogenous risk factors for childhood leukemia, namely gender and birth weight, since boys and heavier newborns are known to be at higher risk. IGF-1 and IGFBP-3 were measured under code in the serum of 118 apparently healthy children aged 0-14 years and the values of each of these components were regressed on age, gender and birth weight. Insulin-like growth factor-2 (IGF-2), as a dependent variable, and anemia during the corresponding pregnancy, as a predictor variable, were also evaluated for exploratory purposes.Results: In the total data set, IGF-1 was positively associated with birth weight (p = 0.0001), whereas girls had higher levels of IGFBP-3 (p = 0.01).Conclusions: It appears that the associations of measured components of the IGF system with the examined risk factors for childhood leukemia are largely compatible with those that would have been expected, if this system played a role in the pathogenesis of childhood leukemia. [ABSTRACT FROM AUTHOR]

Objective: Prediction of cancer risk is a minor component of current health risk appraisals. Perception of individual cancer risk is poor. A Cancer Risk Index was developed to predict individual cancer risk for cancers accounting for 80% of the cancer burden in the United States.Methods: We used group consensus among researchers at the Harvard Medical School and Harvard School of Public Health to identify risk factors as definite, probable and possible causes of cancer. Risk points were allocated according to the strength of the causal association and summed. Population average risk of cancer and cumulative 10-year risk was obtained from SEER data. Individual ranking relative to the population average was determined. The risk index was evaluated for validity using colon cancer incidence in prospective cohort data.Results: The Harvard Cancer Risk Index provides a broad classification of cancer risk. Validation against cohort data shows good agreement for colon cancer.Conclusion: The Harvard Cancer Risk Index offers a simple estimation of personal risk of cancer. It may help inform users of the major risk factors for cancer and identify changes in lifestyle that will reduce their risk. It offers the potential for tailored health-promotion messages. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to describe the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) in the etiology of hepatocellular carcinoma (HCC).Methods: During a 4-year period from January 1995 to December 1998, blood samples and questionnaire data were obtained from 333 incident cases of HCC from Athens, Greece, as well as from patients in two control groups, also from Athens. Controls were 272 metastatic liver cancer (MLC) patients and 360 patients hospitalized for injuries or eye, ear, nose or throat conditions. Coded sera were tested for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) by third-generation enzyme immunoassays.Results: The odds ratios (with 95% confidence intervals) in logistic regression modeling comparing the HCC cases to the combined control series were 48.8 (30.5-78.3) for the presence of HBsAg and 23.2 (11.4-47.3) for the presence of anti-HCV. The odds ratio for concurrent infection with HBV and HCV was 46.2 (9.9-216.6) compared to infection with neither virus.Conclusions: Although HBV and HCV are both important causes of HCC in this study population the data do not suggest, neither do they conclusively refute, a super-additive interaction between the two infections in the development of this malignancy. In this population, 58% of HCC cases can be attributed to HBV, 12% to HCV, and 3% to dual infection with these viruses. [ABSTRACT FROM AUTHOR]

Objective: Breast size has been hypothesized to predict a woman's risk of breast cancer although studies in the main have not supported an association. In a large, population-based case-control study we examined whether breast size might emerge as a significant risk factor among very lean women in whom breast size might be a truer reflection of the volume of gland mass at risk for malignant change.Methods: The data derive from a population-based case-control study of women aged 50 to 79 years conducted in several New England states and Wisconsin. Incident cases of invasive breast cancer (n = 2015) were identified through state tumor registries and controls (n = 2556) were selected at random within age strata from population lists. Telephone interviews were conducted to obtain information on known and suspected risk factors which included bra dimensions (cup and back size) prior to a first birth, or at the age of 20 for nulliparous women.Results: We observed a significant positive association for cup size which was limited to women who were the most lean as young adults based on chest circumference. Among those reporting a chest size under 34 inches multivariate-adjusted relative risks were 1.34 (95% CI: 1.04 to 1.74) for cup size B, and 1.76 (95% CI: 1.04 to 3.01) for cup size C and larger, compared to a cup size smaller than B, and the trend for increasing cup size was statistically significant (P = 0.005). There was no relation with breast size among women reporting an average or larger back circumference (34 inches or larger).Conclusion: Breast size before a pregnancy is a positive predictor of postmenopausal breast cancer, but this association is limited to those who were especially lean as young women. [ABSTRACT FROM AUTHOR]

Characteristics probably associated with the fetal hormonal milieu have recently been shown to increase (birth size indicators, prematurity, neonatal jaundice) or decrease (pregnancy toxaemia) breast cancer risk in the female offspring. However, it is unknown whether differences in pregnancy hormone levels may contribute to the marked geographical variation in breast cancer incidence. We have compared, in a highly standardized manner, pregnancy hormone levels in a population with high incidence and one with low incidence of breast cancer. Three hundred and four pregnant Caucasian women in Boston and 334 pregnant Chinese women in Shanghai were enrolled from March 1994 to October 1995. Levels of oestradiol, oestriol, prolactin, progesterone, human growth hormone, albumin and sex hormone-binding globulin were measured in maternal blood at weeks 16 and 27 of gestation and compared between the two study sites using non-parametric Wilcoxon's rank-sum test. Demographical, anthropometrical and pregnancy characteristics were ascertained through interview, and relevant variables concerning delivery and the newborn were abstracted from medical records and paediatric charts. During the first visit, median serum levels of all studied hormones were statistically significant, and in most instances substantially, higher among Chinese women, who have a low incidence of breast cancer, compared with American women, who have a high incidence of breast cancer. An analogous pattern was evident during the second visit, although the relative differences tended to be smaller. Further research is needed to identify lifestyle or other exogenous determinants of pregnancy hormone levels, as well as possible mechanisms by which they may influence carcinogenic processes in the breast and possibly other organs. [ABSTRACT FROM AUTHOR]

Although several dietary compounds are hypothesized to have anticarcinogenic properties, the role of specific micronutrients in the development of breast cancer remains unclear. To address this issue, we assessed intake of retinol, β-carotene, vitamin C and vitamin E in relation to breast cancer risk in a case-control study in Greece. Eight hundred and twenty women with histologically confirmed breast cancer were compared with 1548 control women. Dietary data were collected through a 115-item semiquantitative food frequency questionnaire. Data were modelled by logistic regression, with adjustment for total energy intake and established breast cancer risk factors, as well as mutual adjustment among the micronutrients. Among post-menopausal women, there was no association between any of the micronutrients evaluated and risk of breast cancer. Among premenopausal women, β-carotene, vitamin C and vitamin E were each inversely associated with breast cancer risk, but after mutual adjustment among the three nutrients onlyb-carotene remained significant; the odds ratio (OR) for a one-quintile increase in b-carotene intake was 0.84 (95% confidence interval 0.73-0.97). The inverse association observed with b-carotene intake, however, is slightly weaker than the association previously observed with vegetable intake in these data, raising the possibility that the observed β-carotene effect is accounted for by another component of vegetables. [ABSTRACT FROM AUTHOR]

This article reviews the epidemiology of cancer of the pancreas, both descriptive and analytical, at all times cognizant of the problems of misdiagnosis, particularly underdiagnosis, of this lethal disease that continue to hinder epidemiological studies. Pancreas cancer is consistently reported to occur more frequently in men than in women, in blacks than in whites, and in urban rather than rural population groups. In some countries, the mortality rates continue to rise, whereas in others, declining levels of disease can be seen among members of younger birth cohorts. Although some of these patterns can be explained by variation in pancreas cancer risk factors, many cannot. Analytical studies consistently demonstrate that cigaret smoking increases the risk of cancer of the pancreas, and this appears, at the present time, to be the only clearly demonstrated risk factor for pancreatic cancer. Although the association with disease risk and coffee consumption, alcohol consumption, occupational exposures, diabetes, pancreatitis, and other factors requires clarification, it appears likely that the most fruitful research area in the coming years may involve exploration of pancreatic cancer risk and nutritional practices. [ABSTRACT FROM AUTHOR]

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