Role of community pharmacies in a population-based colorectal cancer screening program.

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.

An exploratory study in breast cancer of factors involved in the use and communication with health professionals of Internet information.

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.

Physical Test to Estimate Suitable Workloads for an Exercise Program in Breast Cancer Survivors.

Guillamó, E, Travier, N, Oviedo, GR, Fonseca-Nunes, A, Alamo, JM, Cos, F, Roca, A, Niño, 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.

Communication Channels Used by Women to Contact a Population-Based Breast Cancer Screening Program in Catalonia, Spain.

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.

Changes in metabolic risk, insulin resistance, leptin and adiponectin following a lifestyle intervention in overweight and obese breast cancer survivors.

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.

Feasibility and Effects of Structured Physical Exercise Interventions in Adults with Relapsing-Remitting Multiple Sclerosis: A Pilot Study.

Multiple sclerosis (MS) is a chronic neurological disease which affects young adults at a time of maximum personal, professional and social growth. Recent guidelines on physical activity have established that exercise is an essential component of the clinical management of people with MS with mild or moderate degree of disability. The main purpose of this study was to test the feasibility and the effects of two different 40-week structured physical exercise interventions (a supervised high intensity interval training plus home exercise program and a self-applied home-based exercise program) on clinical evolution, psychological wellbeing, quality of life, fatigue, cardiorespiratory fitness, strength and balance of people with MS. Twenty-nine participants with relapsing-remitting MS (RRMS) participated in this study. All of them were fully ambulatory and with minimal disability (Expanded Disability Status Scale <3), for at least the last six months. Participants selected to be part of a combined face-to-face plus home exercise group (CFTFG; n = 8); a self-applied home-based exercise group (HG; n = 11) or a control group (CG; n = 10). A total of 23 participants completed the protocol (79.3%), of which 8 participants (100%) from the CFTFG, 7 (63.6%) from the HG and 8 (80%) from the CG. During the first 20-weeks of training, adherence from the CFTFG reached 77.5% and from the HG reached 50 %. During the second 20-weeks of training, adherence from the CFTFG reached 62.5% and from the HG reached 45.4%. After 20-weeks of training, a significant improvement in the absolute VO2 peak and in the 30-second sit to stand test was observed in the CFTFG (all p < .05). This study confirms that offering a 40-week structured exercise programme to a group of fully ambulatory and minimally disabled persons with RRMS is feasible and safe. Any adverse event related to the trial was reported by the participants.

Work, household, and leisure-time physical activity and risk of mortality in the EPIC-Spain cohort.

OBJECTIVE: Large-scale longitudinal data on the association of domain-specific physical activity (PA) and mortality is limited. Our objective was to evaluate the association of work, household (HPA), and leisure time PA (LTPA) with overall and cause-specific mortality in the EPIC-Spain study. METHODS: 38,379 participants (62.4% women), 30-65years old, and free of chronic disease at baseline were followed-up from recruitment (1992 - 1996) to December 31st, 2008 to ascertain vital status and cause of death. PA was evaluated at baseline and at a 3-year follow-up with a validated questionnaire (EPIC-PAQ) and combined variables were used to classify the participants by sub-domains of PA. Associations with overall, cancer, and cardiovascular mortality risks were assessed using competing risk Cox regression models adjusted by potential confounders. RESULTS: After 13.6years of mean follow-up, 1371 deaths were available for analyses. HPA was strongly associated to reduced overall (hazard ratio (HR) for Q4 vs. Q1=0.47 (0.34, 0.64)) and cause-specific mortalities in women and to lower cancer mortality in men (P for trend=0.004), irrespective of age, education, and lifestyle and morbidity variables. LTPA was associated with lower mortality in women (HR for Q4 vs. Q1=0.71 (0.52, 0.98)), but not men. No relationships were found between sedentariness at work and overall mortality. CONCLUSIONS: HPA was associated to lower mortality risk in men and women from the EPIC-Spain cohort, whereas LTPA also contributed to reduce risk of death in women. Considering the large proportion of total daily PA that HPA represents in some population groups, these results are of public health importance.

Physical activity and risk of Amyotrophic Lateral Sclerosis in a prospective cohort study.

Previous case-control studies have suggested a possible increased risk of Amyotrophic Lateral Sclerosis (ALS) with physical activity (PA), but this association has never been studied in prospective cohort studies. We therefore assessed the association between PA and risk of death from ALS in the European Prospective Investigation into Cancer and Nutrition. A total of 472,100 individuals were included in the analysis, yielding 219 ALS deaths. At recruitment, information on PA was collected thorough standardised questionnaires. Total PA was expressed by the Cambridge Physical Activity Index (CPAI) and analysed in relation to ALS mortality, using Cox hazard models. Interactions with age, sex, and anthropometric measures were assessed. Total PA was weakly inversely associated with ALS mortality with a borderline statistically significant trend across categories (p = 0.042), with those physically active being 33% less likely to die from ALS compared to those inactive: HR = 0.67 (95% CI 0.42-1.06). Anthropometric measures, sex, and age did not modify the association with CPAI. The present study shows a slightly decreased-not increased like in case-control studies-risk of dying from ALS in those with high levels of total PA at enrolment. This association does not appear confounded by age, gender, anthropometry, smoking, and education. Ours was the first prospective cohort study on ALS and physical activity.

Main nutrient patterns are associated with prospective weight change in adults from 10 European countries.

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.

Risk of second primary malignancies in women with breast cancer: Results from the European prospective investigation into cancer and nutrition (EPIC).

Women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications. We have followed-up for 11 years 10,045 women with invasive breast cancer from a European cohort, and identified 492 second primary cancers, including 140 contralateral breast cancers. Expected and observed cases and Standardized Incidence Ratios (SIR) were estimated using Aalen-Johansen Markovian methods. Information on various risk factors was obtained from detailed questionnaires and anthropometric measurements. Cox proportional hazards regression models were used to estimate the role of risk factors. Women with breast cancer had a 30% excess risk for second malignancies (95% confidence interval-CI 18-42) after excluding contralateral breast cancers. Risk was particularly elevated for colorectal cancer (SIR, 1.71, 95% CI 1.43-2.00), lymphoma (SIR 1.80, 95% CI 1.31-2.40), melanoma (2.12; 1.63-2.70), endometrium (2.18; 1.75-2.70) and kidney cancers (2.40; 1.57-3.52). Risk of second malignancies was positively associated with age at first cancer, body mass index and smoking status, while it was inversely associated with education, post-menopausal status and a history of full-term pregnancy. We describe in a large cohort of women with breast cancer a 30% excess of second primaries. Among risk factors for breast cancer, a history of full-term pregnancy was inversely associated with the risk of second primary cancer.

Pre-diagnostic polyphenol intake and breast cancer survival: the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

The aim was to investigate the association between pre-diagnostic intakes of polyphenol classes (flavonoids, lignans, phenolic acids, stilbenes, and other polyphenols) in relation to breast cancer survival (all-cause and breast cancer-specific mortality). We used data from the European Prospective Investigation into Cancer and Nutrition cohort. Pre-diagnostic usual diet was assessed using dietary questionnaires, and polyphenol intakes were estimated using the Phenol-Explorer database. We followed 11,782 breast cancer cases from time of diagnosis until death, end of follow-up or last day of contact. During a median of 6 years, 1482 women died (753 of breast cancer). We related polyphenol intake to all-cause and breast cancer-specific mortality using Cox proportional hazard models with time since diagnosis as underlying time and strata for age and country. Among postmenopausal women, an intake of lignans in the highest versus lowest quartile was related to a 28 % lower risk of dying from breast (adjusted model: HR, quartile 4 vs. quartile 1, 0.72, 95 % CI 0.53; 0.98). In contrast, in premenopausal women, a positive association between lignan intake and all-cause mortality was found (adjusted model: HR, quartile 4 vs. quartile 1, 1.63, 95 % CI 1.03; 2.57). We found no association for other polyphenol classes. Intake of lignans before breast cancer diagnosis may be related to improved survival among postmenopausal women, but may on the contrary worsen the survival for premenopausal women. This suggests that the role of phytoestrogens in breast cancer survival is complex and may be dependent of menopausal status.

Effects of an 18-week exercise programme started early during breast cancer treatment: a randomised controlled trial.

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.

Is Quality of Life Related to Cardiorespiratory Fitness in Overweight and Obese Breast Cancer Survivors?

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.

Smoking as a major risk factor for cervical cancer and pre-cancer: results from the EPIC cohort.

A total of 308,036 women were selected from the European Prospective Investigation into Cancer and Nutrition (EPIC) study to evaluate the association between tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). At baseline, participants completed a questionnaire and provided blood samples. During a mean follow-up time of 9 years, 261 ICC cases and 804 CIN3/CIS cases were reported. In a nested case-control study, the baseline 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 (CT), and Human Herpes Virus 2 (HHV-2). Cervical samples were not available for HPV-DNA analysis in this study. Multivariate analyses were used to estimate associations between smoking and risk of CIN3/CIS and ICC in the cohort and the case-control studies. In the cohort analyses smoking status, duration and intensity showed a two-fold increased risk of CIN3/CIS and ICC, while time since quitting was associated with a two-fold reduced risk. In the nested case-control study, consistent associations were observed after adjustment for HPV, CT and HHV-2 serostatus, in both HPV seronegative and seropositive women. Results from this large prospective study confirm the role of tobacco smoking as an important risk factor for both CIN3/CIS and ICC, even after taking into account HPV exposure as determined by HPV serology. The strong beneficial effect of quitting smoking is an important finding that will further support public health policies for smoking cessation.

Weight change in middle adulthood and breast cancer risk in the EPIC-PANACEA study.

Long-term weight gain (i.e., weight gain since age 20) has been related to higher risk of postmenopausal breast cancer, but a lower risk of premenopausal breast cancer. The effect of weight change in middle adulthood is unclear. We investigated the association between weight change in middle adulthood (i.e., women aged 40-50 years) and the risk of breast cancer before and after the age of 50. We included female participants of the European Prospective Investigation into Cancer and Nutrition cohort, with information on anthropometric measures at recruitment and after a median follow-up of 4.3 years. Annual weight change was categorized using quintiles taking quintile 2 and 3 as the reference category (-0.44 to 0.36 kg/year). Multivariable Cox proportional hazards regression analysis was used to examine the association. 205,723 women were included and 4,663 incident breast cancer cases were diagnosed during a median follow-up of 7.5 years (from second weight assessment onward). High weight gain (Q5: 0.83-4.98 kg/year) was related to a slightly, but significantly higher breast cancer risk (HRQ5_versus_Q2/3 : 1.09, 95% CI: 1.01-1.18). The association was more pronounced for breast cancer diagnosed before or at age 50 (HRQ5_versus_Q2/3 : 1.37, 95% CI: 1.02-1.85). Weight loss was not associated with breast cancer risk. There was no evidence for heterogeneity by hormone receptor status. In conclusion, high weight gain in middle adulthood increases the risk of breast cancer. The association seems to be more pronounced for breast cancer diagnosed before or at age 50. Our results illustrate the importance of avoiding weight gain in middle adulthood.

Physical activity and risk of breast cancer overall and by hormone receptor status: the European prospective investigation into cancer and nutrition.

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.

Abdominal obesity, weight gain during adulthood and risk of liver and biliary tract cancer in a European cohort.

General obesity has been positively associated with risk of liver and probably with biliary tract cancer, but little is known about abdominal obesity or weight gain during adulthood. We used multivariable Cox proportional hazard models to investigate associations between weight, body mass index, waist and hip circumference, waist-to-hip and waist-to-height ratio (WHtR), weight change during adulthood and risk of hepatocellular carcinoma (HCC), intrahepatic (IBDC) and extrahepatic bile duct system cancer [EBDSC including gallbladder cancer (GBC)] among 359,525 men and women in the European Prospective Investigation into Cancer and Nutrition study. Hepatitis B and C virus status was measured in a nested case-control subset. During a mean follow-up of 8.6 years, 177 cases of HCC, 58 cases of IBDC and 210 cases of EBDSC, including 76 cases of GBC, occurred. All anthropometric measures were positively associated with risk of HCC and GBC. WHtR showed the strongest association with HCC [relative risk (RR) comparing extreme tertiles 3.51, 95% confidence interval (95% CI): 2.09-5.87; p(trend) < 0.0001] and with GBC (RR: 1.56, 95% CI: 1.12-2.16 for an increment of one unit in WHtR). Weight gain during adulthood was also positively associated with HCC when comparing extreme tertiles (RR: 2.48, 95% CI: 1.49-4.13; <0.001). No statistically significant association was observed between obesity and risk of IBDC and EBDSC. Our results provide evidence of an association between obesity, particularly abdominal obesity, and risk of HCC and GBC. Our findings support public health recommendations to reduce the prevalence of obesity and weight gain in adulthood for HCC and GBC prevention in Western populations.

Menstrual and reproductive factors in women, genetic variation in CYP17A1, and pancreatic cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort.

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 (<12 vs. 13 years) was moderately associated with an increased risk of pancreatic cancer in the full cohort; however, this result was marginally significant (HR = 1.44; 95% CI = 0.99-2.10). CYP17A1 rs619824 was associated with HRT use (p value = 0.037) in control women; however, none of the SNPs alone, in combination, or as haplotypes were associated with pancreatic cancer risk. In conclusion, with the possible exception of an early age of menarche, none of the menstrual and reproductive factors, and none of the 12 common genetic variants we evaluated at the CYP17A1 locus makes a substantial contribution to pancreatic cancer susceptibility in the EPIC cohort.

Hormonal, metabolic, and inflammatory profiles and endometrial cancer risk within the EPIC cohort--a factor analysis.

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.

Dietary flavonoid and lignan intake and breast cancer risk according to menopause and hormone receptor status in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study.

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.