Long-term use of multivitamins and risk of colorectal adenoma in women

Background: Use of multivitamins may reduce the risk of colorectal adenoma, but the duration of use needed is unclear. Methods: We prospectively examined years of multivitamin use and risk of colorectal adenoma among 43 641 women who had a first endoscopy between 1991 and 2007 in the Nurses' Health Study II. Use of multivitamins was assessed through biennial questionnaires since 1989. Results: We documented 2277 colorectal adenoma cases. Reporting multivitamin use at any time during the study period compared with never reporting its use was associated with a reduced risk of adenoma (multivariable relative risk (RR)=0.86, 95% confidence interval (CI): 0.76–0.97). There was no clear trend with duration of multivitamin use: years of use compared with never use, ⩽4 years (RR=0.84, 95% CI: 0.74–0.96), 5–9 years (RR=0.89, 95% CI: 0.77, 1.02), 10–14 years (RR=0.86, 95% CI: 0.74, 1.01), 15–19 years (RR=0.85, 95% CI: 0.70, 1.02), and 20–26 years (RR=0.80, 95% CI: 0.64, 1.01); (P trend=0.87). The strongest associations (years of use vs never user) were for size of adenoma: large (⩾1 cm) <4 years (RR=0.75, 95% CI: 0.58–0.96) and in alcohol users (⩾1.4 g per day) 20–26 years (RR=0.67, 95% CI: 0.49–0.91). Conclusion: Our findings suggest that use of multivitamins is associated with lower risk of colorectal adenoma, even with relatively short duration of use

Metabolomic Biomarkers of Prostate Cancer: Prediction, Diagnosis, Progression, Prognosis, and Recurrence

Metabolite profiling is being increasing employed in the study of prostate cancer as a means of identifying predictive, diagnostic, and prognostic biomarkers. This review provides a summary and critique of the current literature. Thirty-three human case-control studies of prostate cancer exploring disease prediction, diagnosis, progression, or treatment response were identified. All but one demonstrated the ability of metabolite profiling to distinguish cancer from benign, tumor aggressiveness, cases who recurred, and those who responded well to therapy. In the subset of studies where biomarker discriminatory ability was quantified, high AUCs were reported that would potentially outperform the current gold standards in diagnosis, prognosis, and disease recurrence, including PSA testing. There were substantial similarities between the metabolites and the associated pathways reported as significant by independent studies, and important roles for abnormal cell growth, intensive cell proliferation, and dysregulation of lipid metabolism were highlighted. The weight of the evidence therefore suggests metabolic alterations specific to prostate carcinogenesis and progression that may represent potential metabolic biomarkers. However, replication and validation of the most promising biomarkers is currently lacking and a number of outstanding methodologic issues remain to be addressed to maximize the utility of metabolomics in the study of prostate cancer.National Institutes of Health (U.S.) (Grant P01 CA055075)National Institutes of Health (U.S.) (Grant CA133891)National Institutes of Health (U.S.) (Grant CA141298)National Institutes of Health (U.S.) (Grant CA136578)National Institutes of Health (U.S.) (Grant UM1 CA167552

Benefit-risk assessment of vitamin D supplementation

Summary: Current intake recommendations of 200 to 600IU vitamin D per day may be insufficient for important disease outcomes reduced by vitamin D. Introduction: This study assessed the benefit of higher-dose and higher achieved 25-hydroxyvitamin D levels [25(OH)D] versus any associated risk. Methods and results: Based on double-blind randomized control trials (RCTs), eight for falls (n = 2426) and 12 for non-vertebral fractures (n = 42,279), there was a significant dose-response relationship between higher-dose and higher achieved 25(OH)D and greater fall and fracture prevention. Optimal benefits were observed at the highest dose tested to date for 700 to 1000IU vitamin D per day or mean 25(OH)D between 75 and 110nmol/l (30-44ng/ml). Prospective cohort data on cardiovascular health and colorectal cancer prevention suggested increased benefits with the highest categories of 25(OH)D evaluated (median between 75 and 110nmol/l). In 25 RCTs, mean serum calcium levels were not related to oral vitamin D up to 100,000IU per day or achieved 25(OH)D up to 643nmol/l. Mean levels of 75 to 110nmol/l were reached in most RCTs with 1,800 to 4,000IU vitamin D per day without risk. Conclusion: Our analysis suggests that mean serum 25(OH)D levels of about 75 to 110nmol/l provide optimal benefits for all investigated endpoints without increasing health risks. These levels can be best obtained with oral doses in the range of 1,800 to 4,000IU vitamin D per day; further work is needed, including subject and environment factors, to better define the doses that will achieve optimal blood levels in the large majority of the populatio

Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies

Objective To quantify the dose-response relation between consumption of whole grain and specific types of grains and the risk of cardiovascular disease, total cancer, and all cause and cause specific mortality. Data sources PubMed and Embase searched up to 3 April 2016. Study selection Prospective studies reporting adjusted relative risk estimates for the association between intake of whole grains or specific types of grains and cardiovascular disease, total cancer, all cause or cause specific mortality. Data synthesis Summary relative risks and 95% confidence intervals calculated with a random effects model. Results 45 studies (64 publications) were included. The summary relative risks per 90 g/day increase in whole grain intake (90 g is equivalent to three servings—for example, two slices of bread and one bowl of cereal or one and a half pieces of pita bread made from whole grains) was 0.81 (95% confidence interval 0.75 to 0.87; I2=9%, n=7 studies) for coronary heart disease, 0.88 (0.75 to 1.03; I2=56%, n=6) for stroke, and 0.78 (0.73 to 0.85; I2=40%, n=10) for cardiovascular disease, with similar results when studies were stratified by whether the outcome was incidence or mortality. The relative risks for morality were 0.85 (0.80 to 0.91; I2=37%, n=6) for total cancer, 0.83 (0.77 to 0.90; I2=83%, n=11) for all causes, 0.78 (0.70 to 0.87; I2=0%, n=4) for respiratory disease, 0.49 (0.23 to 1.05; I2=85%, n=4) for diabetes, 0.74 (0.56 to 0.96; I2=0%, n=3) for infectious diseases, 1.15 (0.66 to 2.02; I2=79%, n=2) for diseases of the nervous system disease, and 0.78 (0.75 to 0.82; I2=0%, n=5) for all non-cardiovascular, non-cancer causes. Reductions in risk were observed up to an intake of 210-225 g/day (seven to seven and a half servings per day) for most of the outcomes. Intakes of specific types of whole grains including whole grain bread, whole grain breakfast cereals, and added bran, as well as total bread and total breakfast cereals were also associated with reduced risks of cardiovascular disease and/or all cause mortality, but there was little evidence of an association with refined grains, white rice, total rice, or total grains. Conclusions This meta-analysis provides further evidence that whole grain intake is associated with a reduced risk of coronary heart disease, cardiovascular disease, and total cancer, and mortality from all causes, respiratory diseases, infectious diseases, diabetes, and all non-cardiovascular, non-cancer causes. These findings support dietary guidelines that recommend increased intake of whole grain to reduce the risk of chronic diseases and premature mortality

Dairy consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis

Background: The relation between consumption of different types of dairy and risk of type 2 diabetes (T2D) remains uncertain. Therefore, we aimed to evaluate the association between total dairy and individual types of dairy consumptions and incident T2D in US adults. Methods: We followed 41,436 men in the Health Professionals Follow-Up Study (1986 to 2010), 67,138 women in the Nurses’ Health Study (1980 to 2010), and 85,884 women in the Nurses’ Health Study II (1991 to 2009). Diet was assessed by validated food-frequency questionnaires, and data were updated every four years. Incident T2D was confirmed by a validated supplementary questionnaire. Results: During 3,984,203 person-years of follow-up, we documented 15,156 incident T2D cases. After adjustment for age, body mass index (BMI) and other lifestyle and dietary risk factors, total dairy consumption was not associated with T2D risk and the pooled hazard ratio (HR) (95% confidence interval (CI)) of T2D for one serving/day increase in total dairy was 0.99 (0.98, 1.01). Among different types of dairy products, neither low-fat nor high-fat dairy intake was appreciably associated with risk of T2D. However, yogurt intake was consistently and inversely associated with T2D risk across the three cohorts with the pooled HR of 0.83 (0.75, 0.92) for one serving/day increment (P for trend <0.001). We conducted a meta-analysis of 14 prospective cohorts with 459,790 participants and 35,863 incident T2D cases; the pooled relative risks (RRs) (95% CIs) were 0.98 (0.96, 1.01) and 0.82 (0.70, 0.96) for one serving total dairy/day and one serving yogurt/day, respectively. Conclusions: Higher intake of yogurt is associated with a reduced risk of T2D, whereas other dairy foods and consumption of total dairy are not appreciably associated with incidence of T2D. Electronic supplementary material The online version of this article (doi:10.1186/s12916-014-0215-1) contains supplementary material, which is available to authorized users

Nut consumption and risk of pancreatic cancer in women

Background: Increasing nut intake has been associated with reduced risk of diabetes mellitus, which is a risk factor for pancreatic cancer. Methods: We prospectively followed 75 680 women in the Nurses' Health Study, and examined the association between nut consumption and pancreatic cancer risk. Participants with a previous history of cancer were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. Results: We documented 466 incident cases of pancreatic cancer. After adjusting for age, height, smoking, physical activity, and total energy intake, women who consumed a 28-g (1 oz) serving size of nuts ⩾2 times per week experienced a significantly lower risk of pancreatic cancer (RR, 0.65; 95% CI, 0.47–0.92; P for trend=0.007) when compared with those who largely abstained from nuts. The results did not appreciably change after further adjustment for body mass index (BMI) and history of diabetes mellitus (RR, 0.68; 95% CI, 0.48–0.95; P for trend=0.01). The inverse association persisted within strata defined by BMI, physical activity, smoking, and intakes of red meat, fruits, and vegetables. Conclusion: Frequent nut consumption is inversely associated with risk of pancreatic cancer in this large prospective cohort of women, independent of other potential risk factors for pancreatic cancer

Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer

Background Selective cyclooxygenase inhibitors may retard the progression of cancer, but they have enhanced thrombotic potential. We report on cardiovascular adverse events in patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer. Methods All serious adverse events that were cardiovascular thrombotic events were reviewed in 2434 patients with stage II or III colorectal cancer participating in a randomized, placebo-controlled trial of rofecoxib, 25 mg daily, started after potentially curative tumor resection and chemotherapy or radiotherapy as indicated. The trial was terminated prematurely owing to worldwide withdrawal of rofecoxib. To examine possible persistent risks, we examined cardiovascular thrombotic events reported up to 24 months after the trial was closed. Results The median duration of active treatment was 7.4 months. The 1167 patients receiving rofecoxib and the 1160 patients receiving placebo were well matched, with a median follow-up period of 33.0 months (interquartile range, 27.6 to 40.1) and 33.4 months (27.7 to 40.4), respectively. Of the 23 confirmed cardiovascular thrombotic events, 16 occurred in the rofecoxib group during or within 14 days after the treatment period, with an estimated relative risk of 2.66 (from the Cox proportional-hazards model; 95% confidence interval [CI], 1.03 to 6.86; P = 0.04). Analysis of the Antiplatelet Trialists’ Collaboration end point (the combined incidence of death from cardiovascular, hemorrhagic, and unknown causes; of nonfatal myocardial infarction; and of nonfatal ischemic and hemorrhagic stroke) gave an unadjusted relative risk of 1.60 (95% CI, 0.57 to 4.51; P = 0.37). Fourteen more cardiovascular thrombotic events, six in the rofecoxib group, were reported within the 2 years after trial closure, with an overall unadjusted relative risk of 1.50 (95% CI, 0.76 to 2.94; P = 0.24). Four patients in the rofecoxib group and two in the placebo group died from thrombotic causes during or within 14 days after the treatment period, and during the follow-up period, one patient in the rofecoxib group and five patients in the placebo group died from cardiovascular causes. Conclusions Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular events among patients with a median study treatment of 7.4 months’ duration. (Current Controlled Trials number, ISRCTN98278138.

A prospective study of plasma inflammatory markers and risk of colorectal cancer in men

Background: Chronic inflammation may mediate risk of colorectal cancer (CRC); however, the association between circulating inflammatory markers and risk of CRC has been inconsistent. Methods: We prospectively evaluated the association of plasma C-reactive protein (CRP), interleukin-6 (IL-6), and the soluble tumour necrosis factor receptor 2 (sTNFR-2) with incident CRC among 274 cases and 532 matched controls nested in the Health Professionals Follow-up Study. Results: Multivariate relative risk (RR) of CRC comparing the extreme quartiles of plasma IL-6 was 1.54 (95% confidence interval (CI), 0.99–2.40; Ptrend=0.02). However, after excluding cases diagnosed within 2 years of blood draw, this association was not statistically significant (RR=1.26, 95% CI, 0.78–2.05; Ptrend=0.21). In analyses restricted to cases diagnosed at least 2 years after blood draw, the association of IL-6 with CRC appeared to differ by body mass index such that the significantly positive association was only present among lean individuals (Pinteraction=0.03). We did not observe any significant association between CRP or sTNFR-2 and CRC. Conclusion: Plasma inflammatory markers are not generally associated with risk of CRC among men. However, the possibility that plasma IL-6 is associated with increased risk of CRC among lean men requires further investigation

Post Diagnosis Diet Quality and Colorectal Cancer Survival in Women

Background: Dietary factors are known to influence colorectal cancer (CRC) risk, however, their association with CRC survival is unclear. Therefore, we prospectively examined the association between diet quality scores, dietary patterns and colorectal cancer (CRC) survival. Methods: 1201 women diagnosed with stage I–III CRC between 1986 and 2008, were followed through 2010. Diet was assessed via a food frequency questionnaire administered at least 6 months after diagnosis. We computed the Alternate Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean Diet score (aMED) and Dietary Approaches to Stop Hypertension score (DASH) and derived two dietary patterns, Western (unhealthy) and prudent (healthy), by principal component analysis for each woman. Results: During follow-up, we documented 435 deaths, including 162 from CRC. After adjusting for potential confounders, only a higher AHEI-2010 score was significantly associated with lower overall mortality (HR comparing extreme quintiles = 0.71, 95% CI 0.52–0.98, p trend = 0.01) as well as borderline significantly with lower risk of CRC mortality by the trend test (HR Q5 vs Q1 = 0.72, 95% CI = 0.43–1.21, p trend = 0.07). When AHEI-2010 components were examined separately, inverse associations for overall mortality were primarily accounted for by moderate alcohol intake (HR comparing abstainers vs 5–15 g/d = 1.30, 95%CI = 1.05–1.61) and lower intake of sugar sweetened beverages and fruit juices combined (HR for each additional serving = 1.11, 95% CI = 1.01–1.23). No other diet quality score or dietary pattern was associated with overall or CRC-specific mortality. Conclusion: Higher AHEI-2010 score may be associated with lower overall mortality, moderate alcohol consumption and lower consumption of sugar sweetened beverages and juices combined appeared to account for most of the observed associations