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Objective To evaluate, using an online non-probability sample, the beliefs about and attitudes towards cancer prevention of people professing vaccination scepticism or conspiracy theories. Design Cross sectional survey. Setting Data collected mainly from ForoCoches (a well known Spanish forum) and other platforms, including Reddit (English), 4Chan (English), HispaChan (Spanish), and a Spanish language website for cancer prevention (mejorsincancer.org) from January to March 2022. Participants Among 1494 responders, 209 were unvaccinated against covid-19, 112 preferred alternative rather than conventional medicine, and 62 reported flat earth or reptilian beliefs. Main outcome measures Cancer beliefs assessed using the Cancer Awareness Measure (CAM) and Cancer Awareness Measure Mythical Causes Scale (CAM-MYCS) (both validated tools). Results Awareness of the actual causes of cancer was greater (median CAM score 63.6%) than that of mythical causes (41.7%). The most endorsed mythical causes of cancer were eating food containing additives or sweeteners, feeling stressed, and eating genetically modified food. Awareness of the actual and mythical causes of cancer among the unvaccinated, alternative medicine, and conspiracy groups was lower than among their counterparts. A median of 54.5% of the actual causes was accurately identified among each of the unvaccinated, alternative medicine, and conspiracy groups, and a median of 63.6% was identified in each of the three corresponding counterparts (P=0.13, 0.04, and 0.003, respectively). For mythical causes, medians of 25.0%, 16.7%, and 16.7% were accurately identified in the unvaccinated, alternative medicine, and conspiracy groups, respectively; a median of 41.7% was identified in each of the three corresponding counterparts (P Conclusions Almost half of the participants agreed that “It seems like everything causes cancer,” which highlights the difficulty that society encounters in differentiating actual and mythical causes owing to mass information. People who believed in conspiracies, rejected the covid-19 vaccine, or preferred alternative medicine were more likely to endorse the mythical causes of cancer than their counterparts but were less likely to endorse the actual causes of cancer. These results suggest a direct connection between digital misinformation and consequent erroneous health decisions, which may represent a further preventable fraction of cancer.

Background Short message service (SMS) based interventions are widely used in healthcare and have shown promising results to improve cancer screening programs. However, more research is still needed to implement SMS in the screening process. We present a study protocol to assess the impact on health and economics of three targeted SMS-based interventions in population-based cancer screening programs. Methods/Design The M-TICs study is a randomized controlled trial with a formal process evaluation. Participants aged 50–69 years identified as eligible from the colorectal cancer (CRC) and breast cancer (BC) screening program of the Catalan Institute of Oncology (Catalonia, Spain) will be randomly assigned to receive standard invitation procedure (control group) or SMS-based intervention to promote participation. Two interventions will be conducted in the CRC screening program: 1) Screening invitation reminder: Those who do not participate in the CRC screening within 6 weeks of invite will receive a reminder (SMS or letter); 2) Reminder to complete and return fecal immunochemical test (FIT) kit: SMS reminder versus no intervention to individuals who have picked up a FIT kit at the pharmacy and they have not returned it after 14 days. The third intervention will be performed in the BC screening program. Women who had been screened previously will receive an SMS invitation or a letter invitation to participate in the screening. As a primary objective we will assess the impact on participation for each intervention. The secondary objectives will be to analyze the cost-effectiveness of the interventions and to assess participants’ perceptions. Expected results The results from this randomized controlled trial will provide important empirical evidence for the use of mobile phone technology as a tool for improving population-based cancer screening programs. These results may influence the cancer screening invitation procedure in future routine practice. Trial registration Registry: NCT04343950 (04/09/2020); clinicaltrials.gov.

Objective To study the impact of the spontaneous use of Internet on breast cancer patients and on their relationship with health professionals. Methods A mixed methodology was used. Two questionnaires were designed through three focus groups, and then administered to 186 patients and 59 professionals in order to assess: (1) patients' use of Internet for health-related information and (2) the impact of this information on patients' psychological outcomes and on their relationship with professionals. Results Patients spent more time looking for illness-related information after diagnosis, using interactive communities more than static information websites. Patients and professionals disagreed about the use of Internet in terms of the knowledge it provides, and its psychological impact. The main barrier reported by patients regarding the sharing of online information with their professionals was the belief that it would damage their relationship. Conclusions Both professionals and patients have a protectionist conception of the therapeutic relationship. This attitude tends to dismiss the positive impact that the use of Internet and the new communication tools may have in cancer patients. New resources should provide an "Internet Prescription" and modes of interaction to facilitate a more open digital communication.

Communication is a corner stone of population-based breast cancer screening programs that need to invite all the women from their target population and provide them with balanced information on screening to guaranty informed participation. Invited women also need to be able to contact screening programs to get further information on screening procedures and/or cancel and reschedule appointments. This study describes the communication channels used by women invited for breast cancer screening to contact the program. The study population consisted of 141,684 women, aged 50-69 years, who were invited during 2015-2016 for screening by the Catalan Breast Cancer Screening Program (Spain). Multiple logistic regression models were performed to assess the association between age, screening history, socioeconomic status and reasons for contacting the program and the outcome variables (contact with the program; contact through information and communication technology (ICT) channels). Among the 141,684 women invited for BC screening, 22.5% contacted the screening office mainly to reschedule (42.2%) and cancel (29.2%) appointments. While the communication channel mostly used was the telephone, 24.8% of the women used ICT. ICT was more frequently used by women who had never been screened. Women who wanted to change their appointment were 65% (OR 1.65, 95%CI 1.54-1.76) more likely to use ICT than women who wanted to cancel it. This study showed the need to reinforce communication between women and breast cancer screening programs and the importance of offering communication channels suiting all women's needs to facilitate appointments' rescheduling and cancelling and therefore improve screening programs' efficiency.

Background The influence of nutrition on breast cancer prognosis is still inconclusive and therefore dietary interventions incorporating dietary biomarkers are needed to confirm compliance with dietary goals and clarify biological mechanisms. The present study assessed whether a lifestyle intervention in breast cancer survivors could affect dietary biomarkers of fruit and vegetables and fatty acids. Methods In this phase II single-arm trial, 37 overweight/obese early stage breast cancer patients completed a 12-week diet and exercise intervention. The intervention involved 1-h weekly diet sessions delivered by a dietician and 75-min bi-weekly physical activity sessions of moderate-to-high intensity led by trained monitors. Before and after the intervention, three 24-h dietary recalls were carried out to calculate nutrient intakes and, in addition, blood samples were taken to measure plasma carotenoids, vitamin E and retinol concentrations and erythrocyte membrane fatty acid (EFA) composition. Wilcoxon signed rank tests were used to assess changes in dietary and biomarkers measurements over the intervention period. Results After the intervention, there was a significant increase in the intake of dietary carotenoids (+15.1% compared to baseline) but not plasma carotenoids levels (+6.3%). Regarding the EFA levels, we observed a significant decrease in percentage of saturated fatty acids (-1.4%) and n-6 polyunsaturated fatty acids (-2.9%) and an increase in monounsaturated fatty acids (1.7%) and total and long-chain n-3 polyunsaturated fatty acids (by 13.1% and 13.7%, respectively). A favourable decrease in the ratio of long-chain n-6 to n-3 polyunsaturated fatty acids (-9.1%) was also observed. Conclusions After a short-term diet and exercise intervention in overweight/obese breast cancer survivors, we observed significant changes in dietary nutrients and fatty acid biomarkers, suggesting positive dietary changes that could be relevant for breast cancer prognosis.

The aim of the study was to measure the effect of three cost-neutral behavioral interventions on participation compared to the standard invitation letter in a population-based colorectal cancer screening program in 2014. For that purpose, a four-arm randomized field trial was conducted among 5077 individuals aged 50 to 69 years. Over an 8-week period, each week was randomly allocated to the intervention or the control conditions. Individuals assigned to the intervention conditions additionally received a prompt to write down the date to pick up the screening test in a pharmacy. Two of the three intervention groups also included an additional paragraph in the invitation letter on either: 1) the high proportion of individuals participating regularly (social norms condition) or 2) the importance of regular participation (benefit condition). We measured screening participation before and after receiving a reminder letter six weeks after the screening invitation. An overall 8.0 percentage point increase in CRC screening was achieved as a direct result of receiving a reminder letter; however none of the intervention strategies influenced participation. The only significant difference was found for newly invited individuals. There, participation rates decreased from 34.9% to 24.2% when the invitation mailing mentioned the importance of regular participation (OR: 0.60; 95% CI: 0.38–0.95). While none of the intervention strategies improved participation rates we found that praising the benefit of regular screening may discourage individuals who have never been invited before as the continuous behavior may be perceived as a large request. Nevertheless, the reminder letter boosted participation rates independently of the intervention assigned.

In Catalonia (Spain), population-based colorectal cancer (CRC) screening offers biennial fecal occult blood testing to men and women aged 50-69 years old. The program is organized in screening hubs, most of which use a pharmacy-based model to distribute and collect fecal immunochemical test (FIT) kits The comprehensive evaluation of CRC screening programs, which include the role and implications of pharmacy involvement, is essential to ensure program quality and identify areas for further improvement. The present study aimed to assess the adherence of community pharmacies to the CRC screening program and to analyze data on FIT kit distribution and collection in the Metropolitan area of Barcelona (Catalonia, Spain). Time to FIT completion was assessed by Kaplan-Meier estimation, and with the log-rank test. A Cox regression model was used to adjust for other variables associated with the completion of FIT such as sex, age, deprivation score index and previous screening behavior. Overall, 82.4% of pharmacies adhered with CRC screening program. Out of 82,902 FIT kits distributed to screening invitees 77,524 completed FIT kits were returned to pharmacies (93.5%) with a participation of 39.8% among the 193,766 invitees. From those who completed a FIT, the median time to return the kit was 3 days. FIT completion time was significantly lower among women, older age, high deprivation score index and previous CRC screening (p 0.005). Our findings highlight the large involvement of community pharmacists with CRC screening program as well as a high quality in the process of FIT distribution and collection.

Background There are two main types of strategies to identify target population for lung cancer screening: 1) strategies based on age and cumulative smoking criteria, 2) risk prediction models allowing the calculation of an individual risk. The objective of this study was to compare different strategies to identify the proportion of the Spanish population at high risk of developing lung cancer, susceptible to be included in a lung cancer screening programme. Methods Cross-sectional study. We used the data of the Spanish National Interview Health Survey (ENSE) of 2011–2012 (21,006 individuals) to estimate the proportion of participants at high risk of developing lung cancer. This estimation was performed using the U.S. national lung screening trial (NLST) criteria and a 6-year prediction model (PLCOm2012), both independently and in combination. Results The prevalence of individuals at high risk of developing lung cancer according to the NLST criteria was 4.9% (7.9% for men, 2.4% for women). Among the 1,034 subjects who met the NLST criteria, 533 (427 men and 106 women) had a 6-year lung cancer risk ≥2.0%. The combination of these two selection strategies showed that 2.5% of the Spanish population had a high risk of developing lung cancer. However, this selection process did not take into account different groups of subjects

Guillamo, E, Travier, N, Oviedo, GR, Fonseca-Nunes, A, Alamo, JM, Cos, F, Roca, A, Nino, O, Agudo, A, and Javierre, C. Physical test to estimate suitable workloads for an exercise program in breast cancer survivors. J Strength Cond Res 34(12): 3593-3599, 2020-Epidemiologic studies suggest that patients with breast cancer who gain weight after diagnosis have a higher risk of recurrence and death. Regular physical exercise can help minimize postdiagnosis weight gain. The objective of the study was to assess the effectiveness of a physical test for individualizing the workloads used during a fitness program. To continuously individualize the intensity of the training, a test was designed and integrated into the sessions. The test consisted in monitoring heart rate and workload during 2 bouts of cycling at moderate intensity. The workload parameters recorded during the tests were later used as reference values to plan the intensity of the next in-person training sessions. The 5 tests conducted during the 12 weeks of the intervention showed significant differences in intensity (F = 3.034, p = 0.047). Compared with the first evaluation, the intensities measured during the third, fourth, and fifth tests presented increases of 9.9% (p = 0.02), 13.2% (p = 0.019), and 17.5% (p = 0.002), respectively. A significant increase in workload with respect to body weight was observed in the physical assessment performed after the program (t = 13.2, p = 0.0001). The peak oxygen consumption with respect to body weight (peak V[Combining Dot Above]O2) achieved by the subjects during the assessment at the end of the program had also increased (t = 9.72, p = 0.0001). The intensity test, introduced in the training sessions along with the physical exercise program, was an easy-to-use, practical tool for monitoring intensity. It allows an adjustment of the workload over the program period that respects the individual progression of each patient.

Longitudinal adherence is a critical component of the efficacy of stool-based screening programs because they should be repeated every 1–2 years. Few data have been published on the uptake in multiple rounds of fecal occult blood test-based (FOBT) colorectal cancer (CRC) screening. We calculated two measures of longitudinal adherence to biennial FOBT (guaiac fecal occult blood test:gFOBT or fecal immunochemical test:FIT) to better understand its impact on the programmatic effectiveness of a population-based CRC screening program (2000–2017). Ongoing population-based CRC program of men and women aged 50–69 years. Variables: Age at first CRC screening invitation, sex, number of screening invitations, number of screens, deprivation score, and uptake rate. Logistic regression models were used to assess the independent effect of sex, age at first invitation, deprivation, and the type of screening test offered on adherence. The uptake rate for guaiac fecal occult blood test (gFOBT) was 23.9%, and for the fecal immunochemical test (FIT), it was 37.4%. The overall rate of consistently screened invitees after seven rounds of screening was 14.2%, being 20.6% for those individuals who used FIT and 14.3% for those who used gFOBT. Factors associated with continued participation (consistent vs. inconsistent screenees) showed that the longitudinal adherence was associated with age, screening test used, and number of invitations. Continued participation was lower in individuals who were screened using FIT than among those screened using gFOBT [OR, 0.68; 95% confidence interval (CI), 0.57–0.81]. The overall rate of consistently screened invitees for colorectal cancer screening was higher with FIT than gFOBT. Studying the rate of individuals being current for screening may help to anticipate potential benefits before the long-term outcome data are available.

Adiposity and physical activity are modifiable factors that could be important determinants of breast cancer (BC) prognosis through their effects on endogenous reproductive hormones, chronic inflammation and metabolic changes. Therefore, it is necessary to evaluate whether offering lifestyle interventions to BC survivors could affect the levels of certain biomarkers involved in these mechanisms. We designed a pre-post intervention study offering diet and exercise sessions over 12 weeks to 42 overweight/obese BC survivors. Before and after the intervention, we obtained dietary information, anthropometry and cardiorespiratory fitness (CRF) measurements and blood samples to measure metabolic risk, insulin resistance and adipokines biomarkers. Wilcoxon signed-rank tests and Spearman partial correlation coefficients were used to compare pre- and post-measurements and assess the correlations between changes in biomarkers and changes in anthropometry and CRF. Breast cancer survivors showed significant improvements in metabolic risk biomarkers and insulin resistance indicators along with a non-significant leptin decrease and a significant adiponectin decrease. The improvements in metabolic risk biomarkers, insulin resistance indicators and leptin were moderately correlated (0.32 ≤ |r| ≤ 0.55) with the decrease in body mass index and the increase in CRF. Diet and exercise interventions implemented in overweight/obese BC survivors may improve metabolic risk, insulin resistance and leptin biomarkers.

Little is known about the patterns of sedentary time (ST) and physical activity (PA) levels throughout the week among adults and older adults with Intellectual Disability (ID). We analyzed ST and PA patterns of adults and older adults with ID. Forty-two adults and 42 older adults with mild to severe ID participated in this study. Height and weight were obtained to calculate Body Mass Index (BMI). Body fat and fat-free mass percentages were also obtained. Patterns of PA levels and ST were assessed with GT3X Actigraph accelerometers. Adults performed higher amounts of total PA and moderate to vigorous PA than older adults during the week, on weekdays and in center time (all p > 0.05). No differences between males and females were found for either PA levels or ST. Only 10.7% of the participants met the global recommendations on PA for health. The participants of the current study showed low PA levels and a high prevalence of ST. Interestingly, when comparing age and/or sex groups, no differences were observed for ST. Our findings provide novel and valuable information to be considered in future interventions aiming to increase PA levels and reduce ST.

Source at https://doi.org/10.1371/journal.pone.0173117 Adult height and sitting height may reflect genetic and environmental factors, including early life nutrition, physical and social environments. Previous studies have reported divergent associations for height and chronic disease mortality, with positive associations observed for cancer mortality but inverse associations for circulatory disease mortality. Sitting height might be more strongly associated with insulin resistance; however, data on sitting height and mortality is sparse. Using the European Prospective Investigation into Cancer and Nutrition study, a prospective cohort of 409,748 individuals, we examined adult height and sitting height in relation to all-cause and cause-specific mortality. Height was measured in the majority of participants; sitting height was measured in ~253,000 participants. During an average of 12.5 years of follow-up, 29,810 deaths (11,931 from cancer and 7,346 from circulatory disease) were identified. Hazard ratios (HR) with 95% confidence intervals (CI) for death were calculated using multivariable Cox regression within quintiles of height. Height was positively associated with cancer mortality (men: HRQ5 vs. Q1 = 1.11, 95%CI = 1.00–1.24; women: HRQ5 vs. Q1 = 1.17, 95%CI = 1.07–1.28). In contrast, height was inversely associated with circulatory disease mortality (men: HRQ5 vs. Q1 = 0.63, 95%CI = 0.56–0.71; women: HRQ5 vs. Q1 = 0.81, 95%CI = 0.70–0.93). Although sitting height was not associated with cancer mortality, it was inversely associated with circulatory disease (men: HRQ5 vs. Q1 = 0.64, 95%CI = 0.55–0.75; women: HRQ5 vs. Q1 = 0.60, 95%CI = 0.49–0.74) and respiratory disease mortality (men: HRQ5 vs. Q1 = 0.45, 95%CI = 0.28–0.71; women: HRQ5 vs. Q1 = 0.60, 95%CI = 0.40–0.89). We observed opposing effects of height on cancer and circulatory disease mortality. Sitting height was inversely associated with circulatory disease and respiratory disease mortality.

Journal Article; Research Support, Non-U.S. Gov't; OBJECTIVE We investigated the association between the proportion of long-chain n-3 polyunsaturated fatty acids (PUFA) in plasma phospholipids from blood samples drawn at enrollment and subsequent change in body weight. Sex, age, and BMI were considered as potential effect modifiers. METHOD A total of 1,998 women and men participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a median of 4.9 years. The associations between the proportion of plasma phospholipid long-chain n-3 PUFA and change in weight were investigated using mixed-effect linear regression. RESULTS The proportion of long-chain n-3 PUFA was not associated with change in weight. Among all participants, the 1-year weight change was -0.7 g per 1% point higher long-chain n-3 PUFA level (95% confidence interval: -20.7 to 19.3). The results when stratified by sex, age, or BMI groups were not systematically different. CONCLUSION The results of this study suggest that the proportion of long-chain n-3 PUFA in plasma phospholipids is not associated with subsequent change in body weight within the range of exposure in the general population. Yes

Studies that have examined the association between alcohol consumption and gastric cancer (GC) risk have been inconsistent. We conducted an investigation of 29 genetic variants in alcohol metabolism loci (alcohol dehydrogenase, ADH1 gene cluster: ADH1A, ADH1B and ADH1C; ADH7 and aldehyde dehydrogenase, ALDH2), alcohol intake and GC risk. We analyzed data from a nested case-control study (364 cases and 1272 controls) within the European Prospective Investigation into Cancer and Nutrition cohort. Single nucleotide polymorphisms (SNPs) were genotyped using a customized array. We observed a statistically significant association between a common 3'-flanking SNP near ADH1A (rs1230025) and GC risk [allelic odds ratio (OR)(A v T) = 1.30, 95% confidence interval (CI) = 1.07-1.59]. Two intronic variants, one in ADH1C (rs283411) and one in ALDH2 (rs16941667), also were associated with GC risk (OR(T v C) = 0.59; 95% CI = 0.38-0.91 and OR(T v C) = 1.34; 95% CI = 1.00-1.79, respectively). Individuals carrying variant alleles at both ADH1 (rs1230025) and ALDH2 (rs16941667) were twice as likely to develop GC (OR(A+T) = 2.0; 95% CI = 1.25-3.20) as those not carrying variant alleles. The association between rs1230025 and GC was modified by alcohol intake (

Evidence on the association between dietary flavonoids and lignans and breast cancer (BC) risk is inconclusive, with the possible exception of isoflavones in Asian countries. Therefore, we investigated prospectively dietary total and subclasses of flavonoid and lignan intake and BC risk according to menopause and hormonal receptor status in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 334,850 women, mostly aged between 35 and 70 years from ten European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the US Department of Agriculture, the Phenol-Explorer and the UK Food Standards Agency databases. Cox regression models were used to analyse the association between dietary flavonoid/lignan intake and the risk of developing BC. During an average 11.5-year follow-up, 11,576 incident BC cases were identified. No association was observed between the intake of total flavonoids [hazard ratio comparing fifth to first quintile (HRQ5-Q1) 0.97, 95 % confidence interval (CI): 0.90-1.04; P trend = 0.591], isoflavones (HRQ5-Q1 1.00, 95 % CI: 0.91-1.10; P trend = 0.734), or total lignans (HRQ5-Q1 1.02, 95 % CI: 0.93-1.11; P trend = 0.469) and overall BC risk. The stratification of the results by menopausal status at recruitment or the differentiation of BC cases according to oestrogen and progesterone receptors did not affect the results. This study shows no associations between flavonoid and lignan intake and BC risk, overall or after taking into account menopausal status and BC hormone receptors.

Obesity, a major risk factor for endometrial cancer, is a low-grade inflammatory state characterized by elevated concentrations of cytokines and acute phase reactants. The current study had two aims: first to investigate the associations of C-reactive protein (CRP), interleukin 6 (IL6), and IL1 receptor antagonist (IL1Ra) with endometrial cancer risk and second to examine to which extent these markers can influence the association between obesity and endometrial cancer. We conducted a case–control study, nested within the European Prospective Investigation into Cancer and Nutrition, which comprised 305 incident cases of endometrial cancer and 574 matched controls. CRP, IL6, and IL1Ra were measured in prospectively collected blood specimens by immunoassays. Data were analyzed using conditional logistic regression. All statistical tests were two-sided, and P values Ptrend=0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08–2.54, Ptrend=0.008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22–2.73, Ptrend=0.004). After adjustment for body mass index (BMI), the estimates were strongly reduced and became non-significant. The association between BMI and endometrial cancer was also substantially attenuated (∼10–20%) after adjustment for inflammatory markers, even when the effects of C-peptide or estrone had already been taken into account. We provided epidemiological evidence that chronic inflammation might mediate the association between obesity and endometrial cancer and that endometrial carcinogenesis could be promoted by an inflammatory milieu.

In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC).We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥ 15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7).Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.

The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Health Research Fund (FIS) of the Spanish Ministry of Health (Exp P10710130) In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.

Olive oil is well known for its cardioprotective properties; however, epidemiological data showing that olive oil consumption reduces incident CHD events are still limited. Therefore, we studied the association between olive oil and CHD in the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort study. The analysis included 40 142 participants (38 % male), free of CHD events at baseline, recruited from five EPIC-Spain centres from 1992 to 1996 and followed up until 2004. Baseline dietary and lifestyle information was collected using interview-administered questionnaires. Cox proportional regression models were used to assess the relationship between validated incident CHD events and olive oil intake (energy-adjusted quartiles and each 10 g/d per 8368 kJ (2000 kcal) increment), while adjusting for potential confounders. During a 10·4-year follow-up, 587 (79 % male) CHD events were recorded. Olive oil intake was negatively associated with CHD risk after excluding dietary mis-reporters (hazard ratio (HR) 0·93; 95 % CI 0·87, 1·00 for each 10 g/d per 8368 kJ (2000 kcal) and HR 0·78; 95 % CI 0·59, 1·03 for upperv. lower quartile). The inverse association between olive oil intake (per 10 g/d per 8368 kJ (2000 kcal)) and CHD was more pronounced in never smokers (11 % reduced CHD risk (P = 0·048)), in never/low alcohol drinkers (25 % reduced CHD risk (P P = 0·072)). In conclusion, olive oil consumption was related to a reduced risk of incident CHD events. This emphasises the need to conserve the traditional culinary use of olive oil within the Mediterranean diet to reduce the CHD burden.

Physical activity is associated with reduced risks of invasive breast cancer. However, whether this holds true for breast cancer subtypes defined by the estrogen receptor (ER) and the progesterone receptor (PR) status is controversial. The study included 257,805 women from the multinational EPIC-cohort study with detailed information on occupational, recreational and household physical activity and important cofactors assessed at baseline. During 11.6 years of median follow-up, 8,034 incident invasive breast cancer cases were identified. Data on ER, PR and combined ER/PR expression were available for 6,007 (67.6%), 4,814 (54.2%) and 4,798 (53.9%) cases, respectively. Adjusted hazard ratios (HR) were estimated by proportional hazards models. Breast cancer risk was inversely associated with moderate and high levels of total physical activity (HR = 0.92, 95% confidence interval (CI): 0.86-0.99, HR = 0.87, 95%-CI: 0.79-0.97, respectively; p-trend = 0.002), compared to the lowest quartile. Among women diagnosed with breast cancer after age 50, the largest risk reduction was found with highest activity (HR = 0.86, 95%-CI: 0.77-0.97), whereas for cancers diagnosed before age 50 strongest associations were found for moderate total physical activity (HR = 0.78, 95%-CI: 0.64-0.94). Analyses by hormone receptor status suggested differential associations for total physical activity (p-heterogeneity = 0.04), with a somewhat stronger inverse relationship for ER+/PR+ breast tumors, primarily driven by PR+ tumors (p-heterogeneity < 0.01). Household physical activity was inversely associated with ER-/PR- tumors. The results of this largest prospective study on the protective effects of physical activity indicate that moderate and high physical activity are associated with modest decreased breast cancer risk. Heterogeneities by receptor status indicate hormone-related mechanisms. What's new? Physical activity is associated with a reduced risk of breast cancer, but whether this holds true for hormone receptor-positive cancers, the most common breast cancer subtypes, is controversial. In this analysis of more than 8,000 breast cancer cases, positive receptor status for estrogen and progesterone was inversely associated with moderate and high physical activity. While benefits were modest, the data suggest that the adoption of even moderate activity levels in high-risk populations could reduce breast cancer incidence. Copyright © 2012 UICC.

Background: Olive oil consumption is associated with a decreased risk of several chronic diseases, in particular cardiovascular disease (CVD). However, data on the effects of olive oil on overall mortality are scarce. Objective: We evaluated the association between olive oil and overall and cause-specific mortality in the Spanish population in the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain). Design: A total of 40,622 participants (62% female) aged 29‐69 y were recruited from 5 Spanish regions in 1992‐1996. The association between olive oil (analyzed as a categorical and continuous variable) and overall and cause-specific mortality (CVD, cancer, and other causes) was analyzed by using Cox proportional hazards regression models adjusted for potential confounders. Results: A total of 1915 deaths were reported during 13.4 y of follow-up; 416 CVD deaths, 956 cancer deaths, and 417 deaths from other causes (for 126 deaths the cause was not available). In comparison with nonconsumers, the highest quartile of olive oil consumption was associated with a 26% (95% CI: 13%, 36%) reduction in risk of overall mortality and a 44% (95% CI: 21%, 60%) reduction in CVD mortality. For each increase in olive oil of 10 g 2000 kcal 21 d 21 , there was a 7% (95% CI: 3%, 10%) decreased risk of overall mortality and a 13% (95% CI: 6%, 20%) decreased risk of CVD mortality. No significant association was observed between olive oil and cancer mortality. Conclusions: Olive oil was associated with a decreased risk of overall mortality and an important reduction in CVD mortality in this large Mediterranean cohort. This provides further evidence on the beneficial effects of one of the key Mediterranean dietary components. Am J Clin Nutr doi: 10.3945/ajcn.111.024216.

Results from case-control and prospective studies suggest a moderate positive association between obesity and height and differentiated thyroid carcinoma (TC). Little is known on the relationship between other measures of adiposity and differentiated TC risk. Here, we present the results of a study on body size and risk of differentiated TC based on a large European prospective study (EPIC). During follow-up, 508 incident cases of differentiated TC were identified in women, and 58 in men. 78% of cases were papillary TC. Cox proportional hazard models were used to estimate hazard ratios (HRs). In women, differentiated TC risk was significantly associated with body mass index (BMI, kg/m(2) ) (HR highest vs lowest quintile = 1.41, 95% CI: 1.03-1.94); height (HR = 1.61; 95% CI: 1.18-2.20); HR highest vs lowest tertile waist (HR = 1.34, 95% CI: 1.00-1.79) and waist-to-hip ratio (HR = 1.42, 95% CI: 1.05-1.91). The association with BMI was somewhat stronger in women below age 50. Corresponding associations for papillary TC were similar to those for all differentiated TC. In men the only body size factors significantly associated with differentiated TC were height (non linear), and leg length (HR highest vs. lowest tertile = 3.03, 95% CI: 1.30-7.07). Our study lends further support to the presence of a moderate positive association between differentiated TC risk and overweight and obesity in women. The risk increase among taller individuals of both sexes suggests that some genetic characteristics or early environmental exposures may also be implicated in the etiology of differentiated TC.

Although there is some evidence suggesting that olive oil could reduce breast cancer (BC) risk, the epidemiological data are still relatively limited, not entirely consistent and mainly based on case-control studies. Therefore, we prospectively assessed the association between olive oil and BC risk in postmenopausal women from the Mediterranean cohorts within the European Prospective Investigation into Cancer and Nutrition. The analysis included 62,284 postmenopausal women recruited from Spain, Italy and Greece who had complete dietary data (collected from validated country-specific dietary questionnaires). The risk of BC (overall and by hormone receptor subtypes) was assessed using hazards ratios (HRs) obtained from Cox proportional hazards regression, while adjusting for known BC risk factors. After a mean follow-up of 9 years, 1,256 women were diagnosed with a primary incident invasive BC. The multivariate HRs for BC risk by olive oil intake (highest vs. lowest tertile of g/day/2,000 kcal) were 1.07 (95% CI = 0.91-1.25) in the adjusted model, 1.06 (95% CI = 0.91-1.24) in the model additionally adjusted for reproductive-related factors and 1.10 (95% CI = 0.92-1.31) for the model additionally adjusted for dietary factors. There was no association between olive oil and risk of estrogen or progesterone receptor-positive tumors, but a suggestion of a negative association with estrogens and progesterone receptor-negative tumors. The results from our prospective study showed that olive oil consumption during adult life was not associated with the risk of BC. However, larger prospective studies are still needed to explore possible differences related to hormone receptor status.

AB Purpose: Fatigue is a common problem among colon cancer patients and typically increases during chemotherapy. Exercise during chemotherapy might have beneficial effects on fatigue. To investigate the short- and long-term effects of an exercise program in colon cancer patients during adjuvant treatment, the Physical Activity During Cancer Treatment study was conducted. Methods: In this multicenter randomized controlled trial, 33 colon cancer patients undergoing chemotherapy (21 men and 12 women) were randomly assigned to either a group receiving an 18-wk supervised exercise program (n = 17) or to usual care (n = 16). The primary outcome was fatigue as measured by the Multidimensional Fatigue Inventory and the Fatigue Quality List. Secondary outcomes were quality of life, physical fitness, anxiety, depression, body weight, and chemotherapy completion rate. Outcome assessment took place at baseline, postintervention (18 wk) and at 36 wk. Results: Intention-to-treat mixed linear model analyses showed that patients in the intervention group experienced significantly less physical fatigue at 18 wk and general fatigue at 36 wk (mean between group differences, -3.2; 95% confidence interval [CI], -6.2 to -0.2; effect size [ES], -0.9 and -2.7; 95% CI, -5.2 to -0.1; ES, -0.8, respectively), and reported higher physical functioning (12.3; 95% CI, 3.3-21.4; ES, 1.0) compared with patients in the usual care group. Conclusion: The Physical Activity During Cancer Treatment trial shows that an 18-wk supervised exercise program in colon cancer patients during chemotherapy is safe and feasible. The intervention significantly reduced physical fatigue at 18 wk and general fatigue at 36 wk. Considering the number of patients included in the present study, replication in a larger study population is required.

Background: There is an association between a greater adherence to a Mediterranean diet and a reduced risk of developing chronic diseases. However, it is not clear whether this dietary pattern may be protective also against the development of obesity. Objective: We assessed the association between the adherence to the Mediterranean dietary pattern (MDP), prospective weight change, and the incidence of overweight or obesity. Design: We conducted a prospective cohort study [the European Prospective Investigation into Cancer and Nutrition Physical Activity, Nutrition, Alcohol Consumption, Cessation of Smoking, Eating Out of Home, and Obesity (EPIC-PANACEA) project] in 373,803 individuals (103,455 men and 270,348 women; age range: 25-70 y) from 10 European countries. Anthropometric measurements were obtained at recruitment and after a median follow-up time of 5 y. The relative Mediterranean Diet Score (rMED; score range: 0-18) was used to assess adherence to the MDP according to the consumption of 9 dietary components that are characteristic of the Mediterranean diet. The association between the rMED and 5-y weight change was modeled through multiadjusted mixed-effects linear regression. Results: Individuals with a high adherence to the MDP according to the rMED (11-18 points) showed a 5-y weight change of 0.16 kg (95% CI: 0.24, 0.07 kg) and were 10% (95% CI: 4%, 18%) less likely to develop overweight or obesity than were individuals with a low adherence to the MDP (0-6 points). The low meat content of the Mediterranean diet seemed to account for most of its positive effect against weight gain. Conclusion: This study shows that promoting the MDP as a model of healthy eating may help to prevent weight gain and the development of obesity. Am J Clin Nutr 2010;92:912-21.

Background: Farm exposures may protect against childhood asthma, hay fever and eczema. Whether farm exposures also confer protection in adult farmers remains unclear. Moreover, little is known about the role of timing of exposure. We assessed the effects of current and childhood farm exposures on asthma, hay fever and eczema in farmers and a rural nonfarming control population. Methods: We conducted a cross-sectional questionnaire survey in 2509 farming families (response rate 78%) and 1001 nonfarming families (response rate 67%), which included 4288 farmers and 1328 nonfarmers. Results: Farmers were less likely to have asthma symptoms, hay fever and eczema; no significant differences were observed among dairy, sheep and beef, and horticulture farmers. A combination of current and childhood exposure was more strongly associated with shortness of breath (OR 0.50, CL 0.39–0.66), wheeze (OR 0.60, CL 0.49–0.73), asthma medication (OR 0.48, CL 0.37–0.63); and asthma ever (OR 0.56, CL 0.46–0.68) than current exposure alone (OR 0.63, CL 0.47–0.84; OR 0.80, CL 0.65–0.99; OR 0.68, CL 0.51–0.9; OR 0.69, CL 0.56–0.85 respectively) or childhood exposure alone (OR 0.97, CL0.65–1.44; OR 1.01, CL 0.75–1.34; OR 0.78, CL 0.51–1.19; OR 0.87, CL 0.63–1.19 respectively). Moreover, the combined number of years of farm exposure in childhood and adulthood showed a dose-dependent inverse association with symptom prevalence. Conclusions: Although both current and childhood farm exposures may play a role in the observed low prevalence of asthma symptoms in adult farmers, continued long-term exposure may be required to maintain optimal protection.

Background: The purpose of this study was to examine the relationship between glycosylated hemoglobin (HbA1c) level and subsequent cancer risk. Material and methods: HbA1c measurements were made on blood samples of participants in a hepatitis B (HB) screening program (1999–2001). Cancer incidence was determined by linkage to cancer registrations and hospitalization records to the end of 2004. Participants previously diagnosed with diabetes or cancer were excluded. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using Cox regression. Results: Among the 46 575 participants (70% M aori, 12% Pacific, 5% Asian and 12% Other), 634 cancer cases were observed. For all cancers combined, a significant increased risk was found in persons with moderately elevated HbA1c levels (6%–6.9%) (HR 1.40, 95% CI: 1.11–1.76), with a smaller increased risk in persons with highly elevated levels (‡7%) (HR 1.09, 95% CI: 0.80–1.48) as compared with persons having low HbA1c levels (

Background: Longitudinal studies of sleep during normal pregnancy and post-partum are rare, and interpretation of the findings is often hampered by methodological issues. Consequentially, there is still limited information on what constitutes normal sleep quality and quantity across pregnancy and early post-partum, for both nulliparous and multiparous women. Aims: To quantify the change and variability in sleep duration and quality across pregnancy and post-partum for healthy nulliparous and multiparous women. Methods: Nineteen women (eight nulliparous and 11 multiparous) wore an actigraph and completed a sleep diary to objectively measure sleep for seven nights during the second trimester, one week prior to delivery, and at one and six weeks post-partum. Mixed model analysis of variance and logistic regression were used to investigate changes in sleep across this timeframe. Results: The largest changes in sleep occurred in the first week post-partum (1.5 h less sleep than during pregnancy, three times more sleep episodes in 24 h, 70% of women regularly napping during the day, and greatest day-to-day variability in sleep). Compared to multiparas, nulliparas generally had less efficient sleep, spent more time in bed and had greater wake after sleep onset in the second trimester, and spent less time in bed and had fewer sleep episodes a day at one week post-partum. Conclusions: These changes should be used to inform women about the extent of change in sleep, particularly early post-partum, and to help health-care providers identify women experiencing severe sleep loss and disruption and discuss possible coping strategies with them.

Background Exercise started shortly after breast cancer diagnosis might prevent or diminish fatigue complaints. The Physical Activity during Cancer Treatment (PACT) study was designed to primarily examine the effects of an 18-week exercise intervention, offered in the daily clinical practice setting and starting within 6 weeks after diagnosis, on preventing an increase in fatigue. Methods This multi-centre controlled trial randomly assigned 204 breast cancer patients to usual care (n = 102) or supervised aerobic and resistance exercise (n = 102). By design, all patients received chemotherapy between baseline and 18 weeks. Fatigue (i.e., primary outcome at 18 weeks), quality of life, anxiety, depression, and physical fitness were measured at 18 and 36 weeks. Results Intention-to-treat mixed linear model analyses showed that physical fatigue increased significantly less during cancer treatment in the intervention group compared to control (mean between-group differences at 18 weeks: −1.3; 95 % CI −2.5 to −0.1; effect size −0.30). Results for general fatigue were comparable but did not reach statistical significance (-1.0, 95%CI -2.1; 0.1; effect size -0.23). At 18 weeks, submaximal cardiorespiratory fitness and several muscle strength tests (leg extension and flexion) were significantly higher in the intervention group compared to control, whereas peak oxygen uptake did not differ between groups. At 36 weeks these differences were no longer statistically significant. Quality of life outcomes favoured the exercise group but were not significantly different between groups. Conclusions A supervised 18-week exercise programme offered early in routine care during adjuvant breast cancer treatment showed positive effects on physical fatigue, submaximal cardiorespiratory fitness, and muscle strength. Exercise early during treatment of breast cancer can be recommended. At 36 weeks, these effects were no longer statistically significant. This might have been caused by the control participants’ high physical activity levels during follow-up. Trial registration Current Controlled Trials ISRCTN43801571, Dutch Trial Register NTR2138. Trial registered on December 9th, 2009. Electronic supplementary material The online version of this article (doi:10.1186/s12916-015-0362-z) contains supplementary material, which is available to authorized users.

This study assessed changes in quality of life (QoL) and cardiorespiratory fitness (CRF) during a diet and physical activity (PA) intervention in breast cancer (BC) survivors and investigated the relation between these changes. The intervention of this single-arm pre-post study involved supervised, 1-hour weekly, diet sessions and 75-minute bi-weekly PA sessions of moderate-to-high intensity. This 12-week intervention targeted overweight/obese women who had recently completed BC treatment. Pre- and post-CRF and QoL measurements were compared using paired t-tests. Linear regression models, including baseline participants' characteristics and weight change, were used to assess the association between changes in CRF and QoL. The 37 BC survivors who completed the intervention between May 7, 2012 and July 27, 2012 showed significant increases in CRF and QoL. Peak oxygen uptake (mL/kg/min) increased from 19.0 ± 2.8 to 24.0 ± 4.1 while peak workload (watts/kg) increased from 1.3 ± 0.3 to 1.7 ± 0.3. Although statistical significance was not reached, the increase in workload seemed associated with increases in physical, mental, and general health and with a decrease in fatigue. This lifestyle intervention improved BC survivors' QoL and CRF and suggested possible relationships between CRF and QoL. More research needs to confirm these associations and promote lifestyle interventions aiming at improving BC survivors' QoL.

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). 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. 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). Higher dietary folate intake may be associated with a lower risk of sex hormone receptor-negative BC in premenopausal women.

Background: Exposure to microbial agents might inhibit the development of atopy and asthma.Objective: We measured the association between microbial exposure assessed at 3 months and the development of atopic sensitization and doctor-diagnosed (DD) asthma and wheeze in the first 4 years in a birth cohort study of children with atopic mothers.Methods: Endotoxin, fungal (1 -> 3)-beta-D-glucans, extracellular polysaccharides from the genera Penicillium and Aspergillus (EPS-Pen/Asp), and dust on living room floors were measured at 3 months of age. Serum IgE levels against common allergens were determined at 1 and 4 years, and questionnaire information about respiratory morbidity was collected yearly.Results: Microbial levels in mattresses were low and not associated with serum IgE levels, DD asthma, and wheeze. Floor levels of biocontaminants and dust, on the other hand, were inversely associated with DD asthma, being most pronounced for endotoxin (odds ratio [OR], 0.40; 95% CI, 0.210.77) and EPS-Pen/Asp (OR, 0.42; 95% CI, 0.18-0.99). Mutual adjustment for other exposures did not significantly after the results for endotoxin and only moderately affected the results for EPS-Pen/Asp. Persistent wheeze was also consistently less common in the high-exposure group, being significant only for EPS-PenlAsp (OR, 0.37; 95% CI, 0.15-0.96). Transient wheeze and wheeze in the past 12 months were also reduced, but effects were smaller and not significant. Relationships with serum-specific IgE levels, which could only be assessed in 41% at age 4 years, were less pronounced and statistically significant only for EPS-Pen/Asp.Conclusions: Early exposure to common microbial contaminants, including fungal agents, might protect against asthma.Clinical implications: Microbial exposure in early life might protect against asthma and might constitute a novel target for prevention.

Background: Obstructive sleep apnoea syndrome (OSAS) affects an estimated 2–4% of the middle aged population. Meta-analyses of randomised controlled trials have shown that the severe presentation of the syndrome (apnoea hypopnoea index (AHI) >30/hour) is effectively treated with continuous positive airway pressure (CPAP). Until recently there have been insufficient data to determine whether CPAP improves sleepiness in the larger subgroup with mild to moderate OSAS (AHI 5–30/hour). Methods: A systematic search of Medline and a hand search identified seven randomised controlled trials where CPAP was compared with either a placebo or with conservative management in the treatment of mild to moderate OSAS (AHI 5–30/hour). All trials used the Epworth Sleepiness Scale (ESS), four used the Multiple Sleep Latency Test (MSLT), and three used the Maintenance of Wakefulness Test (MWT) to measure sleepiness. Results: Meta-analyses indicated that CPAP significantly reduced subjective daytime sleepiness (ESS) by 1.2 points (95% CI 0.5 to 1.9, p = 0.001), improved objective daytime wakefulness (MWT) by 2.1 minutes (95% CI 0.5 to 3.7, p = 0.011), but did not affect objective daytime sleepiness (MSLT, mean benefit −0.2 minutes, 95% CI −1.0 to 0.6, p = 0.6). The two significant effects were small (effect size Conclusions: CPAP elicits small improvements in subjective sleepiness and objective wakefulness in people with mild to moderate OSAS. However, the effects on sleepiness are of limited clinical significance.

Background Evidence confirms the positive effects of lipid-lowering agents on the risk of cardiovascular disease. Local guidelines in France (AFSSAPS) have defined therapeutic objectives for LDL-cholesterol. These objectives vary with the number of cardiovascular risk factors in addition to dyslipidaemia. We determined the proportions of patients at therapeutic objective in different classes of cardiovascular risk to test the hypothesis that compliance with guidelines varies across the levels of risk. Comparison with international guidelines (ANDEM) was also performed. Methods A group of 3173 dyslipidaemic patients treated with lipid-lowering agents and managed by general practitioners was randomly selected from BKL-Thales panel, a French computerized database. For each patient, history of coronary heart disease and the number of cardiovascular risk factors were documented. Compliance with guidelines was assessed from achievement of therapeutic objective. Results The study population included 79% primary prevention patients (1.6, 25.5, 31.7 and 20.1%, with 1, 2, 3, and >3 risk factors, respectively) and 21.0% secondary prevention patients. Applying AFSSAPS guidelines, the proportions of primary prevention patients not at LDL-cholesterol objectives varied across risk categories (P 3 risk factors, and therapeutic failure reached 39.9% in secondary prevention. Only 26% of patients who were at high cardiovascular risk (>3 risk factors or prior coronary heart disease) and not at therapeutic objective received high doses (>standard recommended doses) of lipid-lowering agents in monotherapy. Applying ANDEM guidelines, 74% of secondary prevention patients were not at treatment goal. Conclusion Compliance with guidelines varied inversely with the level of cardiovascular risk. Besides, most patients not at therapeutic objective were not up-titrated. The use of lipid-lowering agents is inadequate, depriving many patients of an effective protection against cardiovascular diseases.

cope Oleanolic acid (OA) is an important triterpenic compound found in olive oil, however little is known about its concentrations in human plasma. We aimed to determine plasma OA levels in a healthy Spanish population and compare them with estimates of dietary olive oil intake. Methods and results The final study sample included 141 individuals randomly selected from the European Prospective Investigation into Cancer and Nutrition Spanish cohort. Dietary olive oil intake was estimated using validated dietary history questionnaires. OA concentrations were determined in plasma (from the participants’ stored blood samples) using a HPLC-MS method. Correlation coefficients between OA and olive oil intake were calculated, adjusting for center; sex; age; consumption of olives, apples, grapes, and red wine; and fasting state. The mean OA concentration in olive oil nonconsumers was 0.72 ng/mL (SD 0.82), while in the high olive oil intake group it was 1.32 ng/mL (SD 1.14). The fully adjusted partial Spearman correlations coefficients reached 0.36 (p-value < 0.001) overall, varying minimally by sex and fasting state. Conclusion This is the first study providing steady-state concentrations of triterpenes in humans. The results show that there was low-to-moderate correlation between OA concentrations and olive oil intake in this population.

BACKGROUND: Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity.OBJECTIVE: This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer.DESIGN: In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER-) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed for α-carotene, β-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, retinol, α-tocopherol, γ-tocopherol, and vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided.RESULTS: In quintile 5 compared with quintile 1, α-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and β-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER- breast tumors. The other analytes were not statistically associated with ER- breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER- and ER+ tumors was statistically significant only for β-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER-/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution).CONCLUSION: Our results indicate that higher concentrations of plasma β-carotene and α-carotene are associated with lower breast cancer risk of ER- tumors.

Purpose: Increased physical activity (PA) is associated with a reduced risk of several cancers. PA may reduce cancer risk by changing endogenous hormones levels, but relatively little research has focused on this topic. The purpose of this study was to elucidate the relation between PA and endogenous hormone concentrations. Methods: A cross-sectional analysis of 798 pre- and 1,360 post-menopausal women included as controls in case-control studies on endogenous hormones (steroids, progesterone, sex-hormone-binding globulin (SHBG), and growth factors) levels, and cancer risk nested within European Prospective Investigation into Cancer and Nutrition cohort was performed. Multivariate regression analyses were performed to compare geometric mean levels of hormones and SHBG by categories of PA. Results: In pre-menopausal women, active women had 19 % significantly lower concentrations of androstenedione, 14 % lower testosterone, and 20 % lower free testosterone than inactive women, while no differences were observed for estrogens, progesterone, SHBG, and growth factors. In post-menopausal women, active women had 18 % significantly lower estradiol and 20 % lower free estradiol concentrations than inactive women, while no differences were observed for the other hormones and SHBG. More vigorous forms of physical activity were associated with higher insulin-like growth factor-I concentrations. Adjustment for body mass index did not alter the associations. Overall, the percentage of variance in hormone concentrations explained by PA levels was

In 1994, acrylamide (AA) was classified as a probable human carcinogen by the International Agency for Research on Cancer. In 2002, AA was discovered at relatively high concentrations in some starchy, plant-based foods cooked at high temperatures.A prospective analysis was conducted to evaluate the association between the dietary intake of AA and ductal adenocarcinoma of the exocrine pancreatic cancer (PC) risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort using Cox regression modeling. EPIC includes500,000 men and women aged 35-75 at enrollment from 10 European countries. AA intake was estimated for each participant by combining questionnaire-based food consumption data with a harmonized AA database derived from the EU monitoring database of AA levels in foods, and evaluated in quintiles and continuously.After a mean follow-up of 11 years, 865 first incident adenocarcinomas of the exocrine pancreas were observed and included in the present analysis. At baseline, the mean dietary AA intake in EPIC was 26.22 µg/day. No overall association was found between continuous or quintiles of dietary AA intake and PC risk in EPIC (HR:0.95, 95%CI:0.89-1.01 per 10 µg/day). There was no effect measure modification by smoking status, sex, diabetes, alcohol intake or geographic region. However, there was an inverse association (HR: 0.73, 95% CI: 0.61-0.88 per 10 µg/day) between AA intake and PC risk in obese persons as defined using the body mass index (BMI, ≥ 30 kg/m(2)), but not when body fatness was defined using waist and hip circumference or their ratio.Dietary intake of AA was not associated with an increased risk of PC in the EPIC cohort.

Epidemiological evidence suggests that the Mediterranean diet (MD) could reduce the risk of breast cancer (BC). As evidence from the prospective studies remains scarce and conflicting, we investigated the association between adherence to the MD and risk of BC among 335,062 women recruited from 1992 to 2000, in ten European countries, and followed for 11 years on average. Adherence to the MD was estimated through an adapted relative Mediterranean diet (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for BC risk factors. A total of 9,009 postmenopausal and 1,216 premenopausal first primary incident invasive BC were identified (5,862 estrogen or progesterone receptor positive [ER+/PR+] and 1,018 estrogen and progesterone receptor negative [ER-/PR-]). The arMED was inversely associated with the risk of BC overall and in postmenopausal women (high vs. low arMED score; hazard ratio [HR] = 0.94 [95% confidence interval [CI]: 0.88, 1.00] ptrend = 0.048, and HR = 0.93 [95% CI: 0.87, 0.99] ptrend = 0.037, respectively). The association was more pronounced in ER-/PR- tumors (HR = 0.80 [95% CI: 0.65, 0.99] ptrend = 0.043). The arMED score was not associated with BC in premenopausal women. Our findings show that adherence to a MD excluding alcohol was related to a modest reduced risk of BC in postmenopausal women, and this association was stronger in receptor-negative tumors. The results support the potential scope for BC prevention through dietary modification. What's new? Many factors can affect susceptibility to breast cancer, including menopausal status and diet. This study investigated the association between breast cancer and an adapted version of the "Mediterranean diet," excluding alcohol. They found that the diet reduced the risk of breast cancer by 6% overall, and by 7% in postmenopausal women. For tumors lacking the estrogen or progesterone receptors, however, the diet reduced risk by 20% in postmenopausal women. Copyright © 2012 UICC.

Energy restriction from a low-calorie diet and increased energy expenditure induced by physical activity (PA) could promote weight loss/maintenance and be important determinants of breast cancer (BC) prognosis. The aim of this study was to assess participation and adherence of overweight and obese BC survivors to a lifestyle intervention and to demonstrate the capacity of this intervention to induce weight loss and nutritional changes. This single-arm pre-post study, which involved one-hourly weekly diet sessions delivered by a dietician and 75-min bi-weekly PA sessions of moderate-to-high intensity led by PA monitors, was offered to overweight and obese BC survivors shortly after treatment. Before and after the intervention, anthropometry, dietary information, quality of life (QoL) and cardiorespiratory fitness (CRF) were collected. A total of 112 BC survivors were invited to participate: 42 of them started the intervention and 37 completed it. Participants attended more than 90 % of the sessions offered and showed a significant weight loss of 5.6 ± 2.0 kg, as well as significant decreases in body mass index, fat mass and waist circumference. Significant decreases in total energy (-25 %), fat (-35 %), saturated fat (-37 %) and carbohydrate (-21 %) intakes were observed while QoL and CRF showed significant increases. This feasibility study demonstrated the success of a short-term diet and PA intervention to induce weight loss and promote healthful changes in BC survivors. Assessing the long-term effects of these changes, and in particular their possible impact of BC prognosis, and designing interventions reaching a wider number of BC survivors are still issues to be addressed.

Menstrual and reproductive factors and exogenous hormone use have been investigated as pancreatic cancer risk factors in case-control and cohort studies, but results have been inconsistent. We conducted a prospective examination of menstrual and reproductive factors, exogenous hormone use and pancreatic cancer risk (based on 304 cases) in 328,610 women from the EPIC cohort. Then, in a case-control study nested within the EPIC cohort, we examined 12 single nucleotide polymorphisms (SNPs) in CYP17A1 (an essential gene in sex steroid metabolism) for association with pancreatic cancer in women and men (324 cases and 353 controls). Of all factors analyzed, only younger age at menarche (

A "Western" lifestyle characterized by physical inactivity and excess weight is associated with a number of metabolic and hormonal dysregulations, including increased circulating estrogen levels, hyperinsulinemia, hyperglycemia, and chronic inflammation. The same hormonal and metabolic axes might mediate the association between this lifestyle and the development of endometrial cancer. Using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC), a prospective cohort study carried out in 10 European countries during 1992-2000, we conducted a factor analysis to delineate important components that summarize the variation explained by a set of biomarkers and to examine their association with endometrial cancer risk. Prediagnostic levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, sex hormone-binding globulin, estrone, estradiol, C-peptide, insulin-like growth factor-binding proteins 1 and 2, adiponectin, high- and low-density lipoprotein cholesterol, glucose, triglycerides, tumor necrosis factor (TNF) α, soluble TNF receptors 1 and 2, C-reactive protein, interleukin-6, and interleukin-1 receptor antagonist were measured in 233 incident endometrial cancer cases and 446 matched controls. Factor analysis identified 3 components associated with postmenopausal endometrial cancer risk that could be labeled "insulin resistance/metabolic syndrome," "steroids," and "inflammation" factors. A fourth component, "lipids," was not significantly associated with endometrial cancer. In conclusion, besides the well-known associations of risk with sex hormones and insulin-regulated physiological axes, our data further support the hypothesis that inflammation factors play a role in endometrial carcinogenesis.

Journal Article; Research Support, Non-U.S. Gov't; BACKGROUND Identifying individuals at high risk of excess weight gain may help targeting prevention efforts at those at risk of various metabolic diseases associated with weight gain. Our aim was to develop a risk score to identify these individuals and validate it in an external population. METHODS We used lifestyle and nutritional data from 53°758 individuals followed for a median of 5.4 years from six centers of the European Prospective Investigation into Cancer and Nutrition (EPIC) to develop a risk score to predict substantial weight gain (SWG) for the next 5 years (derivation sample). Assuming linear weight gain, SWG was defined as gaining ≥ 10% of baseline weight during follow-up. Proportional hazards models were used to identify significant predictors of SWG separately by EPIC center. Regression coefficients of predictors were pooled using random-effects meta-analysis. Pooled coefficients were used to assign weights to each predictor. The risk score was calculated as a linear combination of the predictors. External validity of the score was evaluated in nine other centers of the EPIC study (validation sample). RESULTS Our final model included age, sex, baseline weight, level of education, baseline smoking, sports activity, alcohol use, and intake of six food groups. The model's discriminatory ability measured by the area under a receiver operating characteristic curve was 0.64 (95% CI = 0.63-0.65) in the derivation sample and 0.57 (95% CI = 0.56-0.58) in the validation sample, with variation between centers. Positive and negative predictive values for the optimal cut-off value of ≥ 200 points were 9% and 96%, respectively. CONCLUSION The present risk score confidently excluded a large proportion of individuals from being at any appreciable risk to develop SWG within the next 5 years. Future studies, however, may attempt to further refine the positive prediction of the score. Yes

PURPOSE: Various food patterns have been associated with weight change in adults, but it is unknown which combinations of nutrients may account for such observations. We investigated associations between main nutrient patterns and prospective weight change in adults.METHODS: This study includes 235,880 participants, 25-70 years old, recruited between 1992 and 2000 in 10 European countries. Intakes of 23 nutrients were estimated from country-specific validated dietary questionnaires using the harmonized EPIC Nutrient DataBase. Four nutrient patterns, explaining 67 % of the total variance of nutrient intakes, were previously identified from principal component analysis. Body weight was measured at recruitment and self-reported 5 years later. The relationship between nutrient patterns and annual weight change was examined separately for men and women using linear mixed models with random effect according to center controlling for confounders.RESULTS: Mean weight gain was 460 g/year (SD 950) and 420 g/year (SD 940) for men and women, respectively. The annual differences in weight gain per one SD increase in the pattern scores were as follows: principal component (PC) 1, characterized by nutrients from plant food sources, was inversely associated with weight gain in men (-22 g/year; 95 % CI -33 to -10) and women (-18 g/year; 95 % CI -26 to -11). In contrast, PC4, characterized by protein, vitamin B2, phosphorus, and calcium, was associated with a weight gain of +41 g/year (95 % CI +2 to +80) and +88 g/year (95 % CI +36 to +140) in men and women, respectively. Associations with PC2, a pattern driven by many micro-nutrients, and with PC3, a pattern driven by vitamin D, were less consistent and/or non-significant.CONCLUSIONS: We identified two main nutrient patterns that are associated with moderate but significant long-term differences in weight gain in adults.

Background: Physical activity has been identified as protective factor for invasive breast cancer risk, whereas comparable studies on in situ carcinoma are rare. Methods: The study included data from 283,827 women of the multinational European Prospective Investigation into C7ancer and Nutrition (EPIC)-cohort study. Detailed information on different types of physical activity conducted during the prior year, such as occupational, recreational, and household activity, as well as on important cofactors, was assessed at baseline. Adjusted HRs for in situ breast cancer were estimated by Cox proportional hazards models. Results: During a median follow-up period of 11.7 years, 1,059 incidents of breast carcinoma in situ were identified. In crude and adjusted multivariable models, no associations were found for occupational, household, and recreational physical activity. Furthermore, total physical activity was not associated with risk of in situ breast cancer. Comparing moderately inactive, moderately active, and active participants with inactive study participants resulted in adjusted HRs of 0.99 [95% confidence interval (CI), 0.83–1.19], 0.99 (95% CI, 0.82–1.20), and 1.07 (95% CI, 0.81–1.40), respectively (P value of trend test: 0.788). No inverse associations were found in any substrata defined by age at diagnosis or body mass index (BMI) status. Conclusions: In this large prospective study, we did not find any evidence of an association between physical activity and in situ breast cancer risk. If not by chance, the contrast between our results for carcinoma in situ and the recognized inverse association for invasive breast cancer suggests that physical activity may have stronger effects on proliferation and late stage carcinogenesis. Cancer Epidemiol Biomarkers Prev; 21(12); 2209–19. ©2012 AACR.

Agudo, Antonio Bonet, Catalina Travier, Noemie Gonzalez, Carlos A Vineis, Paolo Bueno-de-Mesquita, H Bas Trichopoulos, Dimitrios Boffetta, Paolo Clavel-Chapelon, Francoise Boutron-Ruault, Marie-Christine Kaaks, Rudolf Lukanova, Annekatrin Schutze, Madlen Boeing, Heiner Tjonneland, Anne Halkjaer, Jytte Overvad, Kim Dahm, Christina C Quiros, J Ramon Sanchez, Maria-Jose Larranaga, Nerea Navarro, Carmen Ardanaz, Eva Khaw, Kay-Tee Wareham, Nicholas J Key, Timothy J Allen, Naomi E Trichopoulou, Antonia Lagiou, Pagona Palli, Domenico Sieri, Sabina Tumino, Rosario Panico, Salvatore Boshuizen, Hendriek Buchner, Frederike L Peeters, Petra H M Borgquist, Signe Almquist, Martin Hallmans, Goran Johansson, Ingegerd Gram, Inger T Lund, Eiliv Weiderpass, Elisabete Romieu, Isabelle Riboli, Elio eng 11692/Cancer Research UK/United Kingdom G1000143/Medical Research Council/United Kingdom British Heart Foundation/United Kingdom Cancer Research UK/United Kingdom Department of Health/United Kingdom Medical Research Council/United Kingdom Wellcome Trust/United Kingdom Research Support, Non-U.S. Gov't 2012/11/22 06:00 J Clin Oncol. 2012 Dec 20;30(36):4550-7. doi: 10.1200/JCO.2011.41.0183. Epub 2012 Nov 19.; International audience; PURPOSE: Our aim was to assess the impact of cigarette smoking on the risk of the tumors classified by the International Agency for Research on Cancer as causally associated with smoking, referred to as tobacco-related cancers (TRC). METHODS: The study population included 441,211 participants (133,018 men and 308,193 women) from the European Prospective Investigation Into Cancer and Nutrition. We investigated 14,563 participants who developed a TRC during an average follow-up of 11 years. The impact of smoking cigarettes on cancer risk was assessed by the population attributable fraction (AF(p)), calculated using the adjusted hazard ratios and 95% CI for current and former smokers, plus either the prevalence of smoking among cancer cases or estimates from surveys in representative samples of the population in each country. RESULTS: The proportion of all TRC attributable to cigarette smoking was 34.9% (95% CI, 32.5 to 37.4) using the smoking prevalence among cases and 36.2% (95% CI, 33.7 to 38.6) using the smoking prevalence from the population. The AF(p) were above 80% for cancers of the lung and larynx, between 20% and 50% for most respiratory and digestive cancers and tumors from the lower urinary tract, and below 20% for the remaining TRC. CONCLUSION: Using data on cancer incidence for 2008 and our AF(p) estimates, about 270,000 new cancer diagnoses per year can be considered attributable to cigarette smoking in the eight European countries with available data for both men and women (Italy, Spain, United Kingdom, the Netherlands, Greece, Germany, Sweden, Denmark).

Background/objectives:Cross-sectionally, educational attainment is strongly associated with the prevalence of obesity, but this association is less clear for weight change during adult life. The objective of this study is to examine the association between educational attainment and weight change during adult life in the European Prospective Investigation into Cancer and Nutrition (EPIC).Subjects/methods:EPIC is a cohort study with 361 467 participants and up to 10 years of follow-up. Educational attainment was categorized according to the highest obtained school level (primary school or less, vocational secondary training, other secondary education and university). Multivariate mixed-effects linear regression models were used to study education in relation to weight at age 20 years (self-reported), to annual change in weight between age 20 years and measured weight at recruitment, and to annual change in weight during follow-up time.Results:Higher educational attainment was associated with on average a lower body mass index (BMI) at age 20 years and a lower increase in weight up to recruitment (highest vs lowest educational attainment in men: -60 g per year (95% confidence interval (CI) -80; -40), women -110 g per year (95% CI -130; -80)). Although during follow-up after recruitment an increase in body weight was observed in all educational levels, gain was lowest in men and women with a university degree (high vs low education -120 g per year (95% CI -150; -90) and -70 g per year (95% CI -90; -60), respectively).Conclusions:Existing differences in BMI between higher and lower educated individuals at early adulthood became more pronounced during lifetime, which possibly impacts on obesity-related chronic disease risk in persons with lower educational attainment.European Journal of Clinical Nutrition advance online publication, 6 June 2012; doi:10.1038/ejcn.2012.55.

Purpose. We assessed the association between smoking cessation and prospective weight change in the European population of the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of smoking. Eating out of home And obesity (EPIC-PANACEA) project. Methods. The study involved more than 300,000 healthy volunteers, recruited between 1992 and 2000 in 9 European countries, who provided data on anthropometry and smoking habits at baseline and after a follow-up of 5 years on average. Adjusted mixed-effects linear regression models were used to obtain sex-specific summary estimates of the association between the change in smoking status and the annual change in weight. Results. Smoking cessation tends to be followed by weight gain; when compared to stable smokers, annual weight gain was higher in men (0.44 kg (95%CI: 0.36; 0.52)) and women (0.46 kg (95%CI: 0.41; 0.52)) who stopped smoking during follow-up. When smokers who stopped smoking at least 1 year before recruitment were compared to never smokers, no major differences in annual weight gain were observed. The excess weight gain following smoking cessation appears to mainly occur in the first years following the cessation. Conclusions. When considering the benefits of smoking cessation, such findings strengthen the need for promoting cessation offering information on weight gain control and support to weight-concerned smokers in order to remove a barrier to quitting. (C) 2011 Elsevier Inc. All rights reserved.

Background: The evidence that individual dietary and lifestyle factors influence a person's weight and waist circumference is well established; however their combined impact is less well documented. Therefore, we investigated the combined effect of physical activity, nutrition and smoking status on prospective gain in body weight and waist circumference. Methods: We used data of the prospective EPIC-PANACEA study. Between 1992 and 2000, 325,537 participants (94,445 men and 231,092 women, aged between 25-70) were recruited from nine European countries. Participants were categorised into two groups (positive or negative health behaviours) for each of the following being physically active, adherent to a healthy (Mediterranean not including alcohol) diet, and never-smoking for a total score ranging from zero to three. Anthropometric measures were taken at baseline and were mainly self-reported after a medium follow-up time of 5 years. Results: Mixed-effects linear regression models adjusted for age, educational level, alcohol consumption, baseline body mass index and follow-up time showed that men and women who reported to be physically active, never-smoking and adherent to the Mediterranean diet gained over a 5-year period 537 (95% CI -706, -368) and 200 (-478, -87) gram less weight and 0.95 (-1.27, -0.639) and 0.99 (-1.29, -0.69) cm less waist circumference, respectively, compared to participants with zero healthy behaviours. Conclusion: The combination of positive health behaviours was associated with significantly lower weight and waist circumference gain.