Background: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) ...with serum sex hormone concentrations. Methods: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case–control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. Results: Breast cancer risk increased with increasing BMI (Ptrend = .002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non–sex hormone–binding globulin–bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone–binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. Conclusion: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.
There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We ...evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow‐up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non‐significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 95% CI 0.69, 1.03) and risk of aggressive (HR: 0.88 95% CI 0.61, 1.28) and non‐aggressive tumors (HR: 0.78 95% CI 0.54, 1.14). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers.
What's new?
Urothelial cell carcinoma (UCC) is the most common form of bladder cancer. Previous studies suggested that plasma carotenoids, antioxidants found in fruit and vegetables, were associated with a decreased risk of UCC while a high intake of animal protein was associated with an increased cancer risk. Here, the authors conducted the first study to investigate the association between the Mediterranean diet, a diet rich in fresh fruits and vegetables and low in animal products, and UCC in Europe. They found that adherence to a Mediterranean diet was not significantly associated with UCC, regardless of level of tumour aggressiveness. They point out that these findings are in line with the rather weak evidence for questionnaire‐based associations between dietary factors and bladder cancer risk.
The influence of dietary factors remains controversial for screen-detected prostate cancer and inconclusive for clinically detected disease. We aimed to examine these associations using prospectively ...collected food diaries.
A total of 1,717 prostate cancer cases in middle-aged and older UK men were pooled from four prospective cohorts with clinically detected disease (n=663), with routine data follow-up (means 6.6-13.3 years) and a case-control study with screen-detected disease (n=1054), nested in a randomised trial of prostate cancer treatments (ISCTRN 20141297). Multiple-day food diaries (records) completed by men prior to diagnosis were used to estimate intakes of 37 selected nutrients, food groups and items, including carbohydrate, fat, protein, dairy products, fish, meat, fruit and vegetables, energy, fibre, alcohol, lycopene and selenium. Cases were matched on age and diary date to at least one control within study (n=3528). Prostate cancer risk was calculated, using conditional logistic regression (adjusted for baseline covariates) and expressed as odds ratios in each quintile of intake (±95% confidence intervals). Prostate cancer risk was also investigated by localised or advanced stage and by cancer detection method.
There were no strong associations between prostate cancer risk and 37 dietary factors.
Prostate cancer risk, including by disease stage, was not strongly associated with dietary factors measured by food diaries in middle-aged and older UK men.
Objectives: Cross-sectional data suggest a strong association between low levels of physical activity and obesity. The EPIC-PANACEA (European Prospective Investigation into Cancer-Physical Activity, ...Nutrition, Alcohol, Cessation of Smoking, Eating out of home And obesity) project was designed to investigate the associations between physical activity and body mass index (BMI) and waist circumference based on individual data collected across nine European countries. Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC), 519 931 volunteers were recruited between 1992 and 2000, of whom 405 819 had data on main variables of interest. Height, body weight and waist circumference were measured using standardized procedures. Physical activity was assessed using a validated four-category index reflecting a self-reported usual activity during work and leisure time. The associations between physical activity and BMI and waist circumference were estimated using multilevel mixed effects linear regression models, adjusted for age, total energy intake, smoking status, alcohol consumption and educational level. Results: A total of 125 629 men and 280 190 women with a mean age of 52.9 (s.d. 9.7) and 51.5 (s.d. 10.0) years, respectively were included. The mean BMI was 26.6 kg/m2 (s.d. 3.6) in men and 25.0 kg/m2 (s.d. 4.5) in women. Fifty percent of men and 30% of women were categorized as being active or moderately active. A one-category difference in the physical activity index was inversely associated with a difference of 0.18 kg/m2 in the mean BMI (95% confidence interval, CI, 0.11, 0.24) and 1.04-cm (95% CI 0.82, 1.26) difference in waist circumference in men. The equivalent figures for women were 0.31 kg/m2 (95% CI 0.23, 0.38) and 0.90 cm (95% CI 0.71, 1.08), respectively. Conclusions: Physical activity is inversely associated with both BMI and waist circumference across nine European countries. Although we cannot interpret the association causally, our results were observed in a large and diverse cohort independently from many potential confounders.
BackgroundThe latest meta-analysis from the World Cancer Research Fund/American Institute for Cancer Research concluded that red meat was a probable cause and processed meat a convincing cause of ...colorectal cancer. However, evidence for associations between red and processed meat intake and other cancer sites is limited. Furthermore, few studies have examined the association between poultry intake and cancer risk. Therefore, the aim of this study was to examine the associations between red, processed meat and poultry intake and incidence for 20 common cancer sites.MethodsWe analysed data from 475,488 participants (54% women) in UK Biobank. Participants were aged 37–73 years and cancer free at baseline. Cancer diagnosis and death due to cancer during follow-up were determined using data-linkage with cancer and death registries (with follow-up until 30 November 2014 for England and Wales and until 31 December 2014 for Scotland, respectively). Information on meat consumption was based on a touchscreen questionnaire completed at baseline covering type and frequency of meat intake. We used multivariable-adjusted Cox proportional hazards models to determine the association between baseline meat intake and cancer incidence. Analyses of lung cancer risk were restricted to never smokers. All analyses were adjusted for socio-demographic, lifestyle and women-specific factors.ResultsOver a mean 5.7 (SD 1.1) years of follow-up 23,117 participants were diagnosed with any type of malignant cancer. Red meat intake was positively associated with colorectal cancer (Hazard ratio (HR) per 50 g/day increment in intake 1.20, 95% Confidence Interval (CI) 1.02–1.41), breast cancer (1.13, 1.01–1.27) and prostate cancer (1.14, 1.00–1.29). Processed meat intake was positively associated with risk for colorectal cancer (HR per 20 g/day increment in intake 1.16, 95% CI 1.04–1.30). Poultry intake was positively associated with risk for malignant melanoma (HR per 30 g/day increment in intake 1.20, 95% CI 1.00–1.44), prostate cancer (1.11, 1.02–1.22) and non-Hodgkin lymphoma (1.26, 1.03–1.55).DiscussionHigher intakes of red and processed meat were associated with a higher risk of colorectal cancer. Red meat consumption was also positively associated with risk of breast and prostate cancer, but these associations are not supported by most previous prospective studies and may be affected by residual confounding. The positive associations of poultry intake with prostate cancer and non-Hodgkin lymphoma require further investigation.
Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies ...conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations.
In 486,799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes.
Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11.
Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease.
The association between soya foods and breast cancer risk was investigated in a prospective study of 34759 women in Hiroshima and Nagasaki, Japan. Women completed dietary questionnaires in 1969-1970 ...and/or in 1979-1981 and were followed for incident breast cancer until 1993. The analysis involved 427 cases of primary breast cancer in 488989 person-years of observation. The risk for breast cancer was not significantly associated with consumption of soya foods: for tofu, relative risks adjusted for attained age, calendar period, city, age at time of bombings and radiation dose to the breast were 0.99 (95% CI 0.80-1.24) for consumption two to four times per week and 1.07 (0.78-1.47) for consumption five or more times per week, relative to consumption once a week or less; for miso soup, relative risks were 1.03 (0.81-1.31) for consumption two to four times per week and 0.87 (0.68-1.12) for consumption five or more times per week, relative to consumption once a week or less. These results were not materially altered by further adjustments for reproductive variables and were similar in women diagnosed before age 50 and at ages 50 and above. Among 17 other foods and drinks examined only dried fish (decrease in relative risk with increasing consumption) and pickled vegetables (higher relative risk with higher consumption) were significantly related to breast cancer risk; these associations were not prior hypotheses and, because of the large number of comparisons made, they may be due to chance.
Smoking is not associated with prostate cancer incidence in most studies, but associations between smoking and fatal prostate cancer have been reported.
During 1992 and 2000, lifestyle information ...was assessed via questionnaires and personal interview in a cohort of 145,112 European men. Until 2009, 4623 incident cases of prostate cancer were identified, including 1517 cases of low-grade, 396 cases of high grade, 1516 cases of localised, 808 cases of advanced disease, and 432 fatal cases. Multivariable Cox proportional hazards regression models were used to examine the association of smoking status, smoking intensity, and smoking duration with the risk of incident and fatal prostate cancer.
Compared with never smokers, current smokers had a reduced risk of prostate cancer (RR=0.90, 95% CI: 0.83-0.97), which was statistically significant for localised and low-grade disease, but not for advanced or high-grade disease. In contrast, heavy smokers (25+ cigarettes per day) and men who had smoked for a long time (40+ years) had a higher risk of prostate cancer death (RR=1.81, 95% CI: 1.11-2.93; RR=1.38, 95% CI: 1.01-1.87, respectively).
The observation of an increased prostate cancer mortality among heavy smokers confirms the results of previous prospective studies.
In the setting of severe immunosuppression, the polyomavirus JC (JCV) can cause a lytic infection of oligodendrocytes. This demyelinating disease of the CNS white matter (WM) is called progressive ...multifocal leukoencephalopathy (PML). JCV has a very narrow host-cell range and productive infection of neurons has never been demonstrated. Patient, methods, and results: An HIV-1-infected patient presented with signs of pyramidal tract and cerebellar dysfunction. Brain MRI revealed T2 hyperintensities in the WM of both frontal lobes and cerebellar atrophy. His disease progressed despite therapy and he died 6 months later. In addition to classic PML findings in the frontal lobe WM, autopsy revealed scattered foci of tissue destruction in the internal granule cell layer (IGCL) of the cerebellum. In these foci, enlarged granule cell neurons identified by the neuronal markers MAP-2 and NeuN reacted with antibodies specific for the polyomavirus VP1 capsid protein. Electron microscopy showed 40 nm viral particles, consistent with polyomaviruses, in these granule cell neurons. In addition, JCV DNA was detected by PCR after laser capture microdissection of cells from the areas of focal cell loss. Finally, in situ hybridization studies demonstrated that many granule cell neurons were infected with JCV but did not contain viral proteins. Sequence analysis of the JCV regulatory region from cerebellar virions showed a tandem repeat pattern also found in PML lesions of the frontal lobe WM.
JCV can productively infect granule cell neurons of the IGCL of the cerebellum. This suggests a role for JCV infection of neurons in cerebellar atrophy occurring in HIV-infected individuals.
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