Milk intake and incident stroke and CHD in populations of European descent: a Mendelian randomisation study.

Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (ß = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.

Social mobility and healthy behaviours from a gender perspective in the Spanish multicase-control study (MCC-Spain).

There is evidence for the influence of socioeconomic status (SES) on healthy behaviours but the effect of social mobility (SM) is not yet well known. This study aims to analyse the influence of origin and destination SES (O-SES and D-SES) and SM on healthy behaviours and co-occurrence, from an integrated gender and age perspective. Data were obtained from the controls of MCC-Spain between 2008-2013 (3,606 participants). Healthy behaviours considered: healthy diet, moderate alcohol consumption, non-smoking and physical activity. SM was categorized as stable high, upward, stable medium, downward or stable low. Binary and multinomial logistic regression models were adjusted. Those aged <65, with a low O-SES, D-SES and stable low SM are less likely to have healthy behaviours in the case of both women (physically active: OR = 0.65 CI = 0.45-0.94, OR = 0.71 CI = 0.52-0.98, OR = 0.61 CI = 0.41-0.91) and men (non-smokers: OR = 0.44 CI = 0.26-0.76, OR = 0.54 CI = 0.35-0.83, OR = 0.41 CI 0.24-0.72; physically active: OR = 0.57 CI = 0.35-0.92, OR = 0.64 CI = 0.44-0.95, OR = 0.53 CI = 0.23-0.87). However, for those aged ≥65, this probability is higher in women with a low O-SES and D-SES (non-smoker: OR = 8.09 CI = 4.18-15.67, OR = 4.14 CI = 2.28-7.52; moderate alcohol consumption: OR = 3.00 CI = 1.45-6.24, OR = 2.83 CI = 1.49-5.37) and in men with a stable low SM (physically active: OR = 1.52 CI = 1.02-1.26). In the case of men, the same behaviour pattern is observed in those with a low O-SES as those with upward mobility, with a higher probability of co-occurring behaviours (three-to-four behaviours: OR = 2.00 CI = 1.22-3.29; OR = 3.13 CI = 1.31-7.48). The relationship of O-SES, D-SES and SM with healthy behaviours is complex and differs according to age and gender.

Near real-time surveillance of the SARS-CoV-2 epidemic with incomplete data.

Designing public health responses to outbreaks requires close monitoring of population-level health indicators in real-time. Thus, an accurate estimation of the epidemic curve is critical. We propose an approach to reconstruct epidemic curves in near real time. We apply this approach to characterize the early SARS-CoV-2 outbreak in two Spanish regions between March and April 2020. We address two data collection problems that affected the reliability of the available real-time epidemiological data, namely, the frequent missing information documenting when a patient first experienced symptoms, and the frequent retrospective revision of historical information (including right censoring). This is done by using a novel back-calculating procedure based on imputing patients' dates of symptom onset from reported cases, according to a dynamically-estimated "backward" reporting delay conditional distribution, and adjusting for right censoring using an existing package, NobBS , to estimate in real time (nowcast) cases by date of symptom onset. This process allows us to obtain an approximation of the time-varying reproduction number ( R t ) in real-time. At each step, we evaluate how different assumptions affect the recovered epidemiological events and compare the proposed approach to the alternative procedure of merely using curves of case counts, by report day, to characterize the time-evolution of the outbreak. Finally, we assess how these real-time estimates compare with subsequently documented epidemiological information that is considered more reliable and complete that became available later in time. Our approach may help improve accuracy, quantify uncertainty, and evaluate frequently unstated assumptions when recovering the epidemic curves from limited data obtained from public health surveillance systems in other locations.

Partial contributions and temporal trends of leading causes of death during the last four decades in Spain.

OBJECTIVES: The study was conducted to assess time trend shifts of leading causes of death and their partial contributions over the years 1975-2016 in Spain. STUDY DESIGN: A longitudinal ecological epidemiologic design was conducted to analyse linear trend period shifts using joinpoint regression as the annual percentage of change (APC) in the period 1975-2016. The partial contributions were illustrated as the rate ratio of a singular-cause to their major-cause shift periods. RESULTS: HIV/AIDS shaped the increasing trend period of infectious diseases in 1989-1995 (APC = 25.3, P < 0.05) and the decreasing trend in 1995-1999 and 1999-2016. Lung cancer fell gradually from 1994 in men (-0.4, P < 0.05); however, in women, the condition continued increasing from 1990 (P < 0.05). Dementia types influenced mental and neurological disease drifts. The recent trend for circulatory periods (1980-2016) was mainly modulated by cardiac ischaemia, with increased partial contributions (25%, 32% and 30%). Traffic accidents defined the descending tendency of external causes. CONCLUSIONS: Spain showed a Western pattern in descended rates, including non-decreasing trends in mental and neurological diseases, pancreatic cancer, drug abuse and suicide. Trend shifts and partial contributions illustrated targets for further mortality reduction.

The role of plasma microseminoprotein-beta in prostate cancer: an observational nested case-control and Mendelian randomization study in the European prospective investigation into cancer and nutrition.

BACKGROUND: Microseminoprotein-beta (MSP), a protein secreted by the prostate epithelium, may have a protective role in the development of prostate cancer. The only previous prospective study found a 2% reduced prostate cancer risk per unit increase in MSP. This work investigates the association of MSP with prostate cancer risk using observational and Mendelian randomization (MR) methods. PATIENTS AND METHODS: A nested case-control study was conducted with the European Prospective Investigation into Cancer and Nutrition (EPIC) with 1871 cases and 1871 matched controls. Conditional logistic regression analysis was used to investigate the association of pre-diagnostic circulating MSP with risk of incident prostate cancer overall and by tumour subtype. EPIC-derived estimates were combined with published data to calculate an MR estimate using two-sample inverse-variance method. RESULTS: Plasma MSP concentrations were inversely associated with prostate cancer risk after adjusting for total prostate-specific antigen concentration [odds ratio (OR) highest versus lowest fourth of MSP = 0.65, 95% confidence interval (CI) 0.51-0.84, Ptrend = 0.001]. No heterogeneity in this association was observed by tumour stage or histological grade. Plasma MSP concentrations were 66% lower in rs10993994 TT compared with CC homozygotes (per allele difference in MSP: 6.09 ng/ml, 95% CI 5.56-6.61, r2=0.42). MR analyses supported a potentially causal protective association of MSP with prostate cancer risk (OR per 1 ng/ml increase in MSP for MR: 0.96, 95% CI 0.95-0.97 versus EPIC observational: 0.98, 95% CI 0.97-0.99). Limitations include lack of complete tumour subtype information and more complete information on the biological function of MSP. CONCLUSIONS: In this large prospective European study and using MR analyses, men with high circulating MSP concentration have a lower risk of prostate cancer. MSP may play a causally protective role in prostate cancer.

Compositional analysis of dietary patterns.

Instead of looking at individual nutrients or foods, dietary pattern analysis has emerged as a promising approach to examine the relationship between diet and health outcomes. Despite dietary patterns being compositional (i.e. usually a higher intake of some foods implies that less of other foods are being consumed), compositional data analysis has not yet been applied in this setting. We describe three compositional data analysis approaches (compositional principal component analysis, balances and principal balances) that enable the extraction of dietary patterns by using control subjects from the Spanish multicase-control (MCC-Spain) study. In particular, principal balances overcome the limitations of purely data-driven or investigator-driven methods and present dietary patterns as trade-offs between eating more of some foods and less of others.

Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort.

There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from375 incident pancreatic cancer cases and375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (ORT3-T1 [odds ratio for highest versus lowest tertile] =0.63; 95%CI[confidence interval] = 0.41-0.98; ptrend = 0.036), n-3 polyunsaturated α-linolenic acid (ORT3-T1 = 0.60; 95%CI = 0.39-0.92; ptrend = 0.02) and docosapentaenoic acid (ORT3-T1 = 0.52; 95%CI = 0.32-0.85; ptrend = 0.008). Industrial trans-fatty acids were positively associated with pancreatic cancer risk among men (ORT3-T1 = 3.00; 95%CI = 1.13-7.99; ptrend = 0.029), while conjugated linoleic acids were inversely related to pancreatic cancer among women only (ORT3-T1 = 0.37; 95%CI = 0.17-0.81; ptrend = 0.008). Among current smokers, the long-chain n-6/n-3 polyunsaturated fatty acids ratio was positively associated with pancreatic cancer risk (ORT3-T1 = 3.40; 95%CI = 1.39-8.34; ptrend = 0.007). Results were robust to a range of sensitivity analyses. Our findings suggest that higher circulating levels of saturated fatty acids with an odd number of carbon atoms and n-3 polyunsaturated fatty acids may be related to lower risk of pancreatic cancer. The influence of some fatty acids on the development of pancreatic cancer may be sex-specific and modulated by smoking.

Childhood and adolescent lymphoma in Spain: incidence and survival trends over 20 years.

BACKGROUND: Lymphoma is the third most common malignancy in children (0-14 years) and the first in adolescents (15-19 years). This population-based study-the largest ever done in Spain-analyses incidence and survival of lymphomas among Spanish children and adolescents. PATIENTS AND METHODS: 1664 lymphoma cases (1983-2007) for incidence and 1030 for survival (1991-2005) followed until 31/12/2010, were provided by 11 cancer registries. Age-adjusted incidence rates (ASRw) to the world standard population were obtained; incidence trends were modelled using the Joinpoint programme, observed survival (OS) was estimated with Kaplan-Meier and trends tested with a log-rank test. Results are presented according to the International Classification of Childhood Cancer-3. RESULTS: In Spain, the ASRw0-14 for lymphomas was 17.5 per 1.000.000 child-years and 50.0 the specific rate for adolescents. Overall incidence increased significantly during 1983-1997 with no increases thereafter. Patients over 9 years old showed significant rising trends for all subtypes, except for Burkitt lymphoma (BL) in adolescents. During 2001-2005 (age 0-19 years), 5-year OS was 94 (90-98), 73 (64-83) and 86 (78-94) for Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL) and BL, respectively. No improvement in survival was found. The incidence in Spain was higher than overall European rates, but within the range of that in Southern Europe. Comparing OS in Spain 1991-1995 and 2001-2005 with results for Europe of the Automated Childhood Cancer Information System (ACCIS) (1988-1997) and the European cancer registry-based study on survival and care of cancer patients (EUROCARE) (2000-2007), it was similar for HL and lower for NHL and BL. CONCLUSIONS: Systematic monitoring and analysis of lymphoma paediatric data would provide clinical and epidemiological information to improve the health care of these patients and the outcomes for these malignancies in Spain.

Trends in incidence of thick, thin and in situ melanoma in Europe.

BACKGROUND: We analysed trends in incidence for in situ and invasive melanoma in some European countries during the period 1995-2012, stratifying for lesion thickness. MATERIAL AND METHODS: Individual anonymised data from population-based European cancer registries (CRs) were collected and combined in a common database, including information on age, sex, year of diagnosis, histological type, tumour location, behaviour (invasive, in situ) and lesion thickness. Mortality data were retrieved from the publicly available World Health Organization database. RESULTS: Our database covered a population of over 117 million inhabitants and included about 415,000 skin lesions, recorded by 18 European CRs (7 of them with national coverage). During the 1995-2012 period, we observed a statistically significant increase in incidence for both invasive (average annual percent change (AAPC) 4.0% men; 3.0% women) and in situ (AAPC 7.7% men; 6.2% women) cases. DISCUSSION: The increase in invasive lesions seemed mainly driven by thin melanomas (AAPC 10% men; 8.3% women). The incidence of thick melanomas also increased, although more slowly in recent years. Correction for lesions of unknown thickness enhanced the differences between thin and thick cases and flattened the trends. Incidence trends varied considerably across registries, but only Netherlands presented a marked increase above the boundaries of a funnel plot that weighted estimates by their precision. Mortality from invasive melanoma has continued to increase in Norway, Iceland (but only for elder people), the Netherlands and Slovenia.

Cancer survival in adult patients in Spain. Results from nine population-based cancer registries.

INTRODUCTION: With the aim of providing cancer control indicators, this work presents cancer survival in adult (≥15 years) patients in Spain diagnosed during the period 2000-2007 from Spanish cancer registries participating in the EUROCARE project. METHODS: Cancer cases from nine Spanish population-based cancer registries were included and analysed as a whole. All primary malignant neoplasms diagnosed in adult patients were eligible for the analysis. Cancer patients were followed until 31 December 2008. For each type of cancer, 1-, 3- and 5-year observed and relative survival were estimated by sex, age and years from diagnosis. Furthermore, age-standardized 5-year relative survival for the period 2000-2007 has been compared with that of the period 1995-1999. RESULTS: Skin melanoma (84.6 95% CI 83.0-86.2), prostate (84.6% 95% CI 83.6-85.6) and thyroid (84.2% CI 95% 82.0-86.6) cancers showed the highest 5-year relative survival, whereas the worst prognosis was observed in pancreatic (6% 95% CI 5.1-7.0) and oesophageal (9.4% 95% CI 7.9-11.1) cancers. Overall, survival is higher in women (58.0%) than in men (48.9%). The absolute difference in relative survival between 2000-2007 and 1995-1999 was positive for all cancers as a whole (+4.8% in men, +1.6% in women) and for most types of tumours. Survival increased significantly for chronic myeloid leukaemia, non-Hodgkin's lymphoma and rectum cancer in both sexes, and for acute lymphoid leukaemia, prostate, liver and colon cancers in men and Hodgkin's lymphoma and breast cancer in women. Survival patterns by age were similar in Europe and Spain. A decline in survival by age was observed in all tumours, being more pronounced for ovarian, corpus uteri, prostate and urinary bladder and less for head and neck and rectum cancers. CONCLUSION: High variability and differences have been observed in survival among adults in Spain according to the type of cancer diagnosed, from above 84% to below 10%, reflecting high heterogeneity. The differences in prognosis by age, sex and period of diagnosis reveal opportunities for improving cancer care in Spain.

Survival of 86,690 patients with thyroid cancer: A population-based study in 29 European countries from EUROCARE-5.

BACKGROUND: Incidence rates of thyroid cancer (TC) increased in several countries during the last 30 years, while mortality rates remained unchanged, raising important questions for treatment and follow-up of TC patients. This study updates population-based estimates of relative survival (RS) after TC diagnosis in Europe by sex, country, age, period and histology. METHODS: Data from 87 cancer registries in 29 countries were extracted from the EUROCARE-5 dataset. One- and 5-year RS were estimated using the cohort approach for 86,690 adult TC patients diagnosed in 2000-2007 and followed-up to 12/31/2008. RS trends in 1999-2007 and 10-year RS in 2005-2007 were estimated using the period approach. RESULTS: In Europe 2000-2007, 5-year RS after TC was 88% in women and 81% in men. Survival rates varied by country and were strongly correlated (Pearson ρ = 75%) with country-specific incidence rates. Five-year RS decreased with age (in women from >95% at age 15-54 to 57% at age 75+), from 98% in women and 94% in men with papillary TC to 14% in women and 12% in men with anaplastic TC. Proportion of papillary TC varied by country and increased over time, while survival rates were similar across areas and periods. In 1999-2007, 5-year RS increased by five percentage points for all TCs but only by two for papillary and by four for follicular TC. Ten-year RS in 2005-2007 was 89% in women and 79% in men. CONCLUSIONS: The reported increasing TC survival trend and differences by area are mainly explained by the varying histological case-mix of cases.

Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort.

Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1 = 1.26; 95% CI 1.00-1.58; Ptrend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1 = 1.29; 95% CI 1.02-1.62; Ptrend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.

Meal patterns across ten European countries - results from the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study.

OBJECTIVE: To characterize meal patterns across ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study. DESIGN: Cross-sectional study utilizing dietary data collected through a standardized 24 h diet recall during 1995-2000. Eleven predefined intake occasions across a 24 h period were assessed during the interview. In the present descriptive report, meal patterns were analysed in terms of daily number of intake occasions, the proportion reporting each intake occasion and the energy contributions from each intake occasion. SETTING: Twenty-seven centres across ten European countries. SUBJECTS: Women (64 %) and men (36 %) aged 35-74 years (n 36 020). RESULTS: Pronounced differences in meal patterns emerged both across centres within the same country and across different countries, with a trend for fewer intake occasions per day in Mediterranean countries compared with central and northern Europe. Differences were also found for daily energy intake provided by lunch, with 38-43 % for women and 41-45 % for men within Mediterranean countries compared with 16-27 % for women and 20-26 % for men in central and northern European countries. Likewise, a south-north gradient was found for daily energy intake from snacks, with 13-20 % (women) and 10-17 % (men) in Mediterranean countries compared with 24-34 % (women) and 23-35 % (men) in central/northern Europe. CONCLUSIONS: We found distinct differences in meal patterns with marked diversity for intake frequency and lunch and snack consumption between Mediterranean and central/northern European countries. Monitoring of meal patterns across various cultures and populations could provide critical context to the research efforts to characterize relationships between dietary intake and health.

Unprocessed red meat and processed meat consumption and risk of stroke in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND/OBJECTIVES: High intakes of unprocessed red or processed meat may increase the risk of stroke. We aimed to examine the association between unprocessed red meat, processed meat and total red meat consumption and risk of total stroke and ischaemic stroke. SUBJECTS/METHODS: Cox proportional hazards regression analyses were conducted based on the data for 41,020 men and women aged 29-69 years at baseline. RESULTS: During a mean follow-up of 13.8 years, 674 incident cases of stroke (531 ischaemic strokes, 79 haemorrhagic strokes, 42 subarachnoid haemorrhages and 22 mixed or unspecified events) were identified. After multiple adjustment, unprocessed red meat, processed meat and total red meat consumption were not correlated with incidence of total stroke or ischaemic stroke in either men or women. The hazard ratios (HRs) for unprocessed red meat and processed meat and risk of total stroke comparing the highest with the lowest quintiles were, respectively, 0.81 (95% confidence interval (CI) 0.54-1.21; P-trend=0.15) and 0.92 (95% CI 0.64-1.32; P-trend=0.82) in men and 1.21 (95% CI 0.79-1.85; P-trend=0.10) and 0.81 (95% CI 0.51-1.27; P-trend=0.17) in women. The HRs for unprocessed red meat and processed meat and risk of ischaemic stroke were, respectively, 0.80 (95% CI 0.51-1.25; P-trend=0.51) and 0.86 (95% CI 0.57-1.29; P-trend=0.77) in men and 1.24 (95% CI 0.74-2.05; P-trend=0.13) and 0.82 (95% CI 0.47-1.42; P-trend=0.31) in women. CONCLUSIONS: In the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, unprocessed red meat and processed meat consumption were not associated with risk of stroke in men or women.

An epidemiologic risk prediction model for ovarian cancer in Europe: the EPIC study.

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.

Fruit and vegetable consumption in relation to hepatocellular carcinoma in a multi-centre, European cohort study.

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.

Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort.

Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (i.e., dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences. We examined associations between reproductive and hormone-related risk factors for EOC by subtype in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 334,126 women with data on reproductive and hormone-related risk factors (follow-up: 1992-2010), 1,245 incident cases of EOC with known histology and invasiveness were identified. Data on tumor histology, grade, and invasiveness, were available from cancer registries and pathology record review. We observed significant heterogeneity by the dualistic model (i.e., type I [low grade serous or endometrioid, mucinous, clear cell, malignant Brenner] vs. type II [high grade serous or endometrioid]) for full-term pregnancy (phet = 0.02). Full-term pregnancy was more strongly inversely associated with type I than type II tumors (ever vs. never: type I: relative risk (RR) 0.47 [95% confidence interval (CI): 0.33-0.69]; type II, RR: 0.81 [0.61-1.06]). We observed no significant differences in risk in analyses by major histologic subtypes of invasive EOC (serous, mucinous, endometrioid, clear cell). None of the investigated factors were associated with borderline tumors. Established protective factors, including duration of oral contraceptive use and full term pregnancy, were consistently inversely associated with risk across histologic subtypes (e.g., ever full-term pregnancy: serous, RR: 0.73 [0.58-0.92]; mucinous, RR: 0.53 [0.30-0.95]; endometrioid, RR: 0.65 [0.40-1.06]; clear cell, RR: 0.34 [0.18-0.64]; phet = 0.16). These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.

Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort.

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.

Dietary folate intake and breast cancer risk: European prospective investigation into cancer and nutrition.

BACKGROUND: There is limited evidence on the association between dietary folate intake and the risk of breast cancer (BC) by hormone receptor expression in the tumors. We investigated the relationship between dietary folate and BC risk using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: A total of 367993 women age 35 to 70 years were recruited in 10 European countries. During a median follow-up of 11.5 years, 11575 women with BC were identified. Dietary folate intake was estimated from country-specific dietary questionnaires. Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk. BC tumors were classified by receptor status. Subgroup analyses were performed by menopausal status and alcohol intake. Intake of other B vitamins was considered. All statistical tests were two-sided. RESULTS: A borderline inverse association was observed between dietary folate and BC risk (hazard ratio comparing top vs bottom quintile [HRQ5-Q1] = 0.92, 95% CI = 0.83 to 1.01, P trend = .037). In premenopausal women, we observed a statistically significant trend towards lower risk in estrogen receptor-negative BC (HRQ5-Q1 = 0.66, 95% CI = 0.45 to 0.96, P trend = .042) and progesterone receptor-negative BC (HRQ5-Q1 = 0.70, 95% CI = 0.51 to 0.97, P trend = .021). No associations were found in postmenopausal women. A 14% reduction in BC risk was observed when comparing the highest with the lowest dietary folate tertiles in women having a high (>12 alcoholic drinks/week) alcohol intake (HRT3-T1 = 0.86, 95% CI = 0.75 to 0.98, P interaction = .035). CONCLUSIONS: Higher dietary folate intake may be associated with a lower risk of sex hormone receptor-negative BC in premenopausal women.

Descriptive epidemiology of Kaposi sarcoma in Europe. Report from the RARECARE project.

Kaposi sarcoma (KS) is a virus-related malignancy which most frequently arises in skin, though visceral sites can also be involved. Infection with Kaposi sarcoma herpes virus (KSHV or HHV-8) is required for development of KS. Nowadays, most cases worldwide occur in persons who are immunosuppressed, usually because of HIV infection or as a result of therapy to combat rejection of a transplanted organ, but classic Kaposi sarcoma is predominantly a disease of the elderly without apparent immunosuppression. We analyzed 2667 KS incident cases diagnosed during 1995-2002 and registered by 75 population-based European cancer registries contributing to the RARECARE project. Total crude and age-standardized incidence rate was 0.3 per 100,000 per year with an estimated 1642 new cases per year in the EU27 countries. Age-standardized incidence rate was 0.8 per 100,000 in Southern Europe but below 0.3 per 100,000 in all other regions. The elevated rate in southern Europe was attributable to a combination of classic Kaposi sarcoma in some Mediterranean countries and the relatively high incidence of AIDS in several countries. Five-year relative survival for 2000-2002 by the period method was 75%. More than 10,000 persons were estimated to be alive in Europe at the beginning of 2008 with a past diagnosis of KS. The aetiological link with suppressed immunity means that many people alive following diagnosis of KS suffer comorbidity from a pre-existing condition. While KS is a rare cancer, it has a relatively good prognosis and so the number of people affected by it is quite large. Thus it provides a notable example of the importance of networking in diagnosis, therapy and research for rare cancers.