Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans. Associations between prediagnostic plasma levels of 17 primary, secondary, and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations. Positive associations were observed between colon cancer risk and plasma levels of seven conjugated bile acid metabolites: the primary bile acids glycocholic acid (OR_{quartile 4 vs quartile 1}= 2.22, 95% confidence interval [CI] = 1.52 to 3.26), taurocholic acid (OR = 1.78, 95% CI = 1.23 to 2.58), glycochenodeoxycholic acid (OR = 1.68, 95% CI = 1.13 to 2.48), taurochenodeoxycholic acid (OR = 1.62, 95% CI = 1.11 to 2.36), and glycohyocholic acid (OR = 1.65, 95% CI = 1.13 to 2.40), and the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95% CI = 1.12 to 2.54) and taurodeoxycholic acid (OR = 1.54, 95% CI = 1.02 to 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk. This prospective study showed that prediagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.

The Mediterranean diet (MD) has shown to reduce the occurrence of several chronic diseases. To evaluate its potential protective role on dementia incidence we studied 16,160 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain Dementia Cohort study recruited between 1992–1996 and followed up for a mean (±SD) of 21.6 (±3.4) years. A total of 459 incident cases of dementia were ascertained through expert revision of medical records. Data on habitual diet was collected through a validated diet history method to assess adherence to the relative Mediterranean Diet (rMED) score. Hazard ratios (HR) of dementia by rMED levels (low, medium and high adherence levels: ≤6, 7–10 and ≥11 points, respectively) were estimated using multivariable Cox models, whereas time-dependent effects were evaluated using flexible parametric Royston-Parmar (RP) models. Results of the fully adjusted model showed that high versus low adherence to the categorical rMED score was associated with a 20% (HR = 0.80, 95%CI: 0.60–1.06) lower risk of dementia overall and HR of dementia was 8% (HR = 0.92, 0.85–0.99, p = 0.021) lower for each 2-point increment of the continuous rMED score. By sub-types, a favorable association was also found in women for non-AD (HR per 2-points = 0.74, 95%CI: 0.62–0.89), while not statistically significant in men for AD (HR per 2-points = 0.88, 0.76–1.01). The association was stronger in participants with lower education. In conclusion, in this large prospective cohort study MD was inversely associated with dementia incidence after accounting for major cardiovascular risk factors. The results differed by dementia sub-type, sex, and education but there was no significant evidence of effect modification.

We aimed to investigate the association between protein intake and risk of inflammatory bowel disease [IBD] in the European Prospective Investigation into Cancer and Nutrition. A total of 413 593 participants from eight European countries were included. Dietary data were collected at baseline from validated food frequency questionnaires. Dietary data were calibrated to correct errors in measures related to each country-specific questionnaire. Associations between proteins [total, animal, and vegetable] or food sources of animal proteins, and IBD risk were estimated by Cox proportional hazard models. After a mean follow-up of 16 years, 177 patients with Crohn’s disease [CD] and 418 with ulcerative colitis [UC], were identified. There was no association between total protein, animal protein, or vegetable protein intakes and CD or UC risks. Total meat and red meat intakes were associated with UC risk (hazard ratio [HR] for the 4th vs 1st quartile = 1.40, 95% confidence interval [CI] = 0.99-1.98, p-trend = 0.01; and 1.61, 95% CI = 1.10-2.36, p-trend = 0.007, respectively]. There was no association between other food sources of animal protein [processed meat, fish, shellfish, eggs, poultry] and UC. We found no association between food sources of animal proteins and CD risk. Meat and red meat consumptions are associated with higher risks of UC. These results support dietary counselling of low meat intake in people at high-risk of IBD.

The aim of this study was to explore the association between three previously identified dietary patterns (Western, Prudent, and Mediterranean) and colorectal cancer (CRC) risk by sex and cancer subtype. The Spanish cohort of the European Prospective Investigation into Cancer and Nutrition study provided dietary and epidemiological information from 15,629 men and 25,808 women recruited between 1992 and 1996. Among them, 568 CRC cases and 3289 deaths were identified during a median follow-up of 16.98 years. The associations between adherence to the three dietary patterns and CRC risk (overall, by sex, and by tumour location: proximal and distal colon and rectum) were investigated by fitting multivariate Cox proportional hazards regression models stratified by study centre and age. Possible heterogeneity of the effects by sex and follow-up time (1–10 vs. ≥10 years) was also explored. While no clear effect of the Prudent dietary pattern on CRC risk was found, a suggestive detrimental effect of the Western dietary pattern was observed, especially during the first 10 years of follow-up (HR_1SD-increase (95% CI): 1.17 (0.99–1.37)), among females (HR_1SD-increase (95% CI): 1.31 (1.06–1.61)), and for rectal cancer (HR_1SD-increase (95% CI): 1.38 (1.03–1.84)). In addition, high adherence to the Mediterranean pattern seemed to protect against CRC, especially when restricting the analyses to the first 10 years of follow-up (HR_1SD-increase (95% CI): 0.84 (0.73–0.98)), among males (HR_1SD-increase (95% CI): 0.80 (0.65–0.98)), and specifically against distal colon cancer (HR_1SD-increase (95% CI): 0.81 (0.63–1.03)). In conclusion, low adherence to the Western diet and high adherence to the Mediterranean dietary pattern could prevent CRC, especially distal colon and rectal cancer.

Lung cancer risk prediction models might efficiently identify individuals who should be offered lung cancer screening. However, their performance has not been comprehensively evaluated in Europe. We aimed to externally validate and evaluate the performance of several risk prediction models that predict lung cancer incidence or mortality in prospective European cohorts. We analysed 240 137 participants aged 45-80 years with a current or former smoking history from nine European countries in four prospective cohorts from the pooled database of the Lung Cancer Cohort Consortium: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (Finland), the Nord-Trøndelag Health Study (Norway), CONSTANCES (France), and the European Prospective Investigation into Cancer and Nutrition (Denmark, Germany, Italy, Spain, Sweden, the Netherlands, and Norway). We evaluated ten lung cancer risk models, which comprised the Bach, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial 2012 model (PLCO_m2012), the Lung Cancer Risk Assessment Tool (LCRAT), the Lung Cancer Death Risk Assessment Tool (LCDRAT), the Nord-Trøndelag Health Study (HUNT), the Optimized Early Warning Model for Lung Cancer Risk (OWL), the University College London-Death (UCLD), the University College London-Incidence (UCLI), the Liverpool Lung Project version 2 (LLP version 2), and the Liverpool Lung Project version 3 (LLP version 3) models. We quantified model calibration as the ratio of expected to observed cases or deaths and discrimination using the area under the receiver operating characteristic curve (AUC). For each model, we also identified risk thresholds that would screen the same number of individuals as each of the US Preventive Services Task Force 2021 (USPSTF-2021), the US Preventive Services Task Force 2013 (USPSTF-2013), and the Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) criteria. Among the participants, 1734 lung cancer cases and 1072 lung cancer deaths occurred within five years of enrolment. Most models had reasonable calibration in most countries, although the LLP version 2 overpredicted risk by more than 50% in eight countries (expected to observed ≥1·50). The PLCO_m2012, LCDRAT, LCRAT, Bach, HUNT, OWL, UCLD, and UCLI models showed similar discrimination in most countries, with AUCs ranging from 0·68 (95% CI 0·59-0·77) to 0·83 (0·78-0·89), whereas the LLP version 2 and LLP version 3 showed lower discrimination, with AUCs ranging from 0·64 (95% CI 0·57-0·72) to 0·78 (0·74-0·83). When pooling data from all countries (but excluding the HUNT cohort), 33·9% (73 313 of 216 387) of individuals were eligible by USPSTF-2021 criteria, which included 74·8% (1185) of lung cancers and 76·3% (730) of lung cancer deaths occurring over 5 years. Fewer individuals were selected by USPSTF-2013 and NELSON criteria. After applying thresholds to select a population of equal size to USPSTF-2021, the PLCO_m2012, LCDRAT, LCRAT, Bach, HUNT, OWL, UCLD, and UCLI, models identified 77·6%-79·1% of future cases, although they selected slightly older individuals compared with USPSTF-2021 criteria. Results were similar for USPSTF-2013 and NELSON. Several lung cancer risk prediction models showed good performance in European countries and might improve the efficiency of lung cancer screening if used in place of categorical eligibility criteria. US National Cancer Institute, l'Institut National du Cancer, Cancer Research UK.