Rudolf Kaaks

Dietary fibre in food and protection against colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC): an observational study

BACKGROUNDnDietary fibre is thought to protect against colorectal cancer but this view has been challenged by recent prospective and intervention studies that showed no protective effect.nnnMETHODSnWe prospectively examined the association between dietary fibre intake and incidence of colorectal cancer in 519978 individuals aged 25-70 years taking part in the EPIC study, recruited from ten European countries. Participants completed a dietary questionnaire in 1992-98 and were followed up for cancer incidence. Relative risk estimates were obtained from fibre intake, categorised by sex-specific, cohort-wide quintiles, and from linear models relating the hazard ratio to fibre intake expressed as a continuous variable.nnnFINDINGSnFollow-up consisted of 1939011 person-years, and data for 1065 reported cases of colorectal cancer were included in the analysis. Dietary fibre in foods was inversely related to incidence of large bowel cancer (adjusted relative risk 0.75 [95% CI 0.59-0.95] for the highest versus lowest quintile of intake), the protective effect being greatest for the left side of the colon, and least for the rectum. After calibration with more detailed dietary data, the adjusted relative risk for the highest versus lowest quintile of fibre from food intake was 0.58 (0.41-0.85). No food source of fibre was significantly more protective than others, and non-food supplement sources of fibre were not investigated.nnnINTERPRETATIONnIn populations with low average intake of dietary fibre, an approximate doubling of total fibre intake from foods could reduce the risk of colorectal cancer by 40%.

Overweight, obesity, and cancer risk

Over the past few decades the proportion of people with excess body weight has been increasing in both developed and less developed countries. About 50% of men and 35% of women in Europe are currently estimated to be overweight or obese. In addition to an increase in the risk of cardiovascular disease and type II diabetes, the evidence summarised here shows that excess body weight is directly associated with risk of cancer at several organ sites, including colon, breast (in postmenopausal women), endometrium, oesophagus, and kidney. In part, these associations with cancer risk may be explained by alterations in the metabolism of endogenous hormones-including sex steroids, insulin, and insulin-like growth factors-which can lead to distortion of the normal balance between cell proliferation, differentiation, and apoptosis. Avoidance of weight gain thus seems to be an important factor for cancer prevention.

Prospective study of IGF-I, IGF-binding proteins, and breast cancer risk, in northern and southern Sweden.

Objective: To examine the possible relationships of breast cancer risk to prediagnostic plasma levels of insulin; insulin-like growth factor-I (IGF-I); and IGF-binding proteins -1, -2, and -3. Methods: Within two prospective cohorts in Umeå and Malmö we measured plasma concentrations of insulin, IGF-I, and IGFBPs for a total of 513 incident breast cancer cases and 987 matched controls. Results: Globally, risk was unassociated with levels of IGF-I, IGFBP-3, or IGF-I adjusted for IGFBP-3. When breaking down the analysis by subgroups of age at blood donation, an increase in risk was observed for increasing levels of IGF-I in women aged 55 or older, in the Umeå cohort only (odds ratios of 1.00, 1.73, 1.76, 1.90; ptrend = 0.05). This effect weakened, however, when the analysis was restricted to subjects who did not use exogenous hormones for the treatment of menopausal symptoms. Levels of IGF-I and IGFBP-3 were not related to risk in younger women, recruited before age 50, contrary to observations from previous studies. In a subcohort where blood samples had been collected after at least four hours of fasting, breast cancer risk showed no clear associations with levels of insulin, IGFBP-1, or IGFBP-2. Conclusions: Our results do not confirm earlier findings of an association of plasma IGF-I levels with breast cancer risk especially in young women, but suggest a possible association with postmenopausal breast cancer risk, possibly among ERT/HRT users only. Our results do not support the hypothesis that elevated plasma insulin levels, and reduced levels of IGFBP-1 and IGFBP-2, are associated with increased breast cancer risk.

The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies

The objective of this study was to examine the effects of the intakeof dietary fat upon colorectal cancer risk in a combined analysis of datafrom 13 case-control studies previously conducted in populations withdiffering colorectal cancer rates and dietary practices. Original datarecords for 5,287 cases of colorectal cancer and 10,470 controls werecombined. Logistic regression analysis was used to estimate odds ratios (OR)for intakes of total energy, total fat and its components, and cholesterol.Positive associations with energy intake were observed for 11 of the 13studies. However, there was little, if any, evidence of anyenergy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01,1.02, and 0.92 for quintiles of residuals of total fat intake (P trend =0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (Ptrend = 0.39). The analysis suggests that, among these case-control studies,there is no energy-independent association between dietary fat intake andrisk of colorectal cancer. It also suggests that simple substitution of fatby other sources of calories is unlikely to reduce meaningfully the risk ofcolorectal cancer.

Alcohol intake and breast cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC)

ObjectiveMost epidemiologic studies have suggested an increased risk of breast cancer with increasing alcohol intake. Using data from 274,688 women participating in the European Prospective Investigation into Cancer and Nutrition study (EPIC), we investigated the relation between alcohol intake and the risk of breast cancer.MethodsIncidence rate ratios (IRRs) based on Cox proportional hazard models were calculated using reported intake of alcohol, recent (at baseline) and lifetime exposure. We adjusted for known risk factors and stratified according to study center as well as potentially modifying host factors.ResultsDuring 6.4 years of follow up, 4,285 invasive cases of breast cancer within the age group 35–75 years were identified. For all countries together the IRR per 10 g/day higher recent alcohol intake (continuous) was 1.03 (95% confidence interval (CI): 1.01–1.05). When adjusted, no association was seen between lifetime alcohol intake and risk of breast cancer. No difference in risk was shown between users and non-users of HRT, and there was no significant interaction between alcohol intake and BMI, HRT or dietary folate.ConclusionThis large European study supports previous findings that recent alcohol intake increases the risk of breast cancer.

Effects of weight control and physical activity in cancer prevention: Role of endogenous hormone metabolism

Abstract: Excess body weight and/or lack of physical activity are increasingly recognized as major risk factors for cancer of the colon, breast, endometrium, and prostate. This paper reviews the effects of excess body weight and physical inactivity on endogenous hormone metabolism (insulin, the IGF‐I/IGFBP system, and sex steroids) and of endocrine alterations with risk of cancer of the endometrium, breast, prostate, and colon.

Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

To clarify the role of metabolic factors in endometrial carcinogenesis, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), and examined the relation between prediagnostic plasma lipids, lipoproteins, and glucose, the metabolic syndrome (MetS; a cluster of metabolic factors) and endometrial cancer risk. Among pre- and postmenopausal women, 284 women developed endometrial cancer during follow-up. Using risk set sampling, 546 matched control subjects were selected. From conditional logistic regression models, high-density lipoprotein cholesterol (HDL-C) levels were inversely associated with risk body mass index (BMI)-adjusted relative risk (RR) for top versus bottom quartile 0.61 (95% confidence intervals (CI) 0.38-0.97), P(trend) = 0.02). Glucose levels were positively associated with risk (BMI-adjusted RR top versus bottom quartile 1.69 (95% CI 0.99-2.90), P(trend) = 0.03), which appeared stronger among postmenopausal women (BMI-adjusted RR top versus bottom tertile 2.61 (95% CI 1.46-4.66), P(trend) = 0.0006, P(heterogeneity) = 0.13) and never-users of exogenous hormones (P(heterogeneity) = 0.005 for oral contraceptive (OC) use and 0.05 for hormone replacement therapy-use). The associations of HDL-C and glucose with risk were no longer statistically significant after further adjustment for obesity-related hormones. Plasma total cholesterol, Low-density lipoprotein cholesterol (LDL-C), and triglycerides were not significantly related to overall risk. The presence of MetS was associated with risk (RR 2.12 (95% CI 1.51-2.97)), which increased with the number of MetS factors (P(trend) = 0.02). An increasing number of MetS factors other than waist circumference, however, was marginally significantly associated with risk only in women with waist circumference above the median (P(interaction) = 0.01). None of the associations differed significantly by fasting status. These findings suggest that metabolic abnormalities and obesity may act synergistically to increase endometrial cancer risk.

Serum levels of C-peptide, IGFBP-1 and IGFBP-2 and endometrial cancer risk; results from the European prospective investigation into cancer and nutrition

We conducted a case‐control study nested within the European Prospective Investigation into Cancer and Nutrition, to examine the associations between prediagnostic serum concentrations of C‐peptide, insulin‐like growth factor binding protein (IGFBP)‐1 and IGFBP‐2, and endometrial cancer risk. Among pre‐ and post‐menopausal women, who were not currently using exogenous hormones, 286 women developed incident endometrial cancer during an average 5.1 years follow‐up. Using risk set sampling, 555 matched control subjects were selected. In conditional logistic regression models adjusted for matching factors only, endometrial cancer risk increased with increasing serum levels of C‐peptide (relative risks (RR) for the top vs. bottom quartile = 2.13 [95% confidence interval (CI) 1.33–3.41], ptrend = 0.001, and decreasing serum levels of IGFBP‐2 (RR for the top vs. bottom quartile = 0.56 [95% CI 0.35–0.90], ptrend = 0.03, but was not significantly associated with IGFBP‐1 levels (RR for the top vs. bottom quartile = 0.76 [95% CI 0.47–1.21], ptrend = 0.25). In BMI‐adjusted models, only the C‐peptide association remained marginally statistically significant (RR for the top vs. bottom quartile = 1.56 [95% CI 0.94–2.57], ptrend = 0.05 for C‐peptide; 0.84 [95% CI 0.50–1.40], ptrend = 0.74 for IGFBP‐2; and 1.08 [95% CI 0.65–1.78], ptrend = 0.86 for IGFBP‐1 levels). These associations were stronger among nonfasting women (≤≤6 hr since last meal; 63% of subjects) but were not evident among fasting women, although the interactions were not statistically significant. The C‐peptide‐risk association was substantially attenuated after adjustment for free estradiol in postmenopausal women (RR for the top vs. bottom quartile = 1.28 [95% CI 0.67–2.45], ptrend = 0.42. Our results provide modest support to the hypothesis that hyperinsulinaemia is a risk factor for endometrial cancer.

Plasma levels of six carotenoids in nine European countries: report from the European Prospective Investigation into Cancer and Nutrition (EPIC)

BACKGROUNDnIn addition to their possible direct biological effects, plasma carotenoids can be used as biochemical markers of fruit and vegetable consumption for identifying diet-disease associations in epidemiological studies. Few studies have compared levels of these carotenoids between countries in Europe.nnnOBJECTIVEnOur aim was to assess the variability of plasma carotenoid levels within the cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC).nnnMETHODSnPlasma levels of six carotenoids--alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein and zeaxanthin--were measured cross-sectionally in 3043 study subjects from 16 regions in nine European countries. We investigated the relative influence of gender, season, age, body mass index (BMI), alcohol intake and smoking status on plasma levels of the carotenoids.nnnRESULTSnMean plasma level of the sum of the six carotenoids varied twofold between regions (1.35 micromol l(-1) for men in Malmö, Sweden vs. 2.79 micromol l(-1) for men in Ragusa/Naples, Italy; 1.61 micromol l(-1) for women in The Netherlands vs. 3.52 micromol l(-1) in Ragusa/Naples, Italy). Mean levels of individual carotenoids varied up to fourfold (alpha-carotene: 0.06 micromol l(-1) for men in Murcia, Spain vs. 0.25 micromol l(-1) for vegetarian men living in the UK). In multivariate regression analyses, region was the most important predictor of total plasma carotenoid level (partial R(2)=27.3%), followed by BMI (partial R(2)=5.2%), gender (partial R(2)=2.7%) and smoking status (partial R(2)=2.8%). Females had higher total carotenoid levels than males across Europe.nnnCONCLUSIONSnPlasma levels of carotenoids vary substantially between 16 different regions in Italy, Greece, Spain, France, Germany, the UK, Sweden, Denmark and The Netherlands. Compared with region of residence, the other demographic and lifestyle factors and laboratory measurements have limited predictive value for plasma carotenoid levels in Europe.

Total dietary carbohydrate, sugar, starch and fibre intakes in the European Prospective Investigation into Cancer and Nutrition

Objective:To describe dietary carbohydrate intakes and their food sources among 27 centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Methods:Between 1995 and 2000, 36u2009034 subjects, aged between 35–74 years, were administered a standardized, 24-h dietary recall using a computerized interview software programme (EPIC-SOFT). Intakes (g/day) of total carbohydrate, sugars, starch and fibre were estimated using the standardized EPIC Nutrient Database (ENDB). Mean intakes were adjusted for age, total energy intake, height and weight, and were weighted by season and day of recall.Results:Adjusted mean total carbohydrate intakes were highest in Italy and in the UK health-conscious cohort, and were lowest in Spain, Greece and France. Total fibre intakes were highest in the UK health-conscious cohort and lowest in Sweden and the UK general population. Bread contributed the highest proportion of carbohydrates (mainly starches) in every centre. Fruit consumption contributed a greater proportion of total carbohydrates (mainly sugars) among women than among men, and in southern centres compared with northern centres. Bread, fruits and vegetables represented the largest sources of fibre, but food sources varied considerably between centres. In stratified analyses, carbohydrate intakes tended to be higher among subjects who were physically active, never-smokers or non-drinkers of alcohol.Conclusions:Dietary carbohydrate intakes and in particular their food sources varied considerably between these 10 European countries. Intakes also varied according to gender and lifestyle factors. These data will form the basis for future aetiological analyses of the role of dietary carbohydrates in influencing health and disease.