Bidirectional Association Between Depression and Metabolic Syndrome

OBJECTIVE Epidemiological studies have repeatedly investigated the association between depression and metabolic syndrome (MetS). However, the results have been inconsistent. This meta-analysis aimed to summarize the current evidence from cross-sectional and prospective cohort studies that evaluated this association. RESEARCH DESIGN AND METHODS MEDLINE, EMBASE, and PsycINFO databases were searched for articles published up to January 2012. Cross-sectional and cohort studies that reported an association between the two conditions in adults were included. Data on prevalence, incidence, unadjusted or adjusted odds ratio (OR), and 95% CI were extracted or provided by the authors. The pooled OR was calculated separately for cross-sectional and cohort studies using random-effects models. The I2 statistic was used to assess heterogeneity. RESULTS The search yielded 29 cross-sectional studies (n = 155,333): 27 studies reported unadjusted OR with a pooled estimate of 1.42 (95% CI 1.28–1.57; I2 = 55.1%); 11 studies reported adjusted OR with depression as the outcome (1.27 [1.07–1.57]; I2 = 60.9%), and 12 studies reported adjusted OR with MetS as the outcome (1.34 [1.18–1.51]; I2 = 0%). Eleven cohort studies were found (2 studies reported both directions): 9 studies (n = 26,936 with 2,316 new-onset depression case subjects) reported adjusted OR with depression as the outcome (1.49 [1.19–1.87]; I2 = 56.8%), 4 studies (n = 3,834 with 350 MetS case subjects) reported adjusted OR with MetS as the outcome (1.52 [1.20–1.91]; I2 = 0%). CONCLUSIONS Our results indicate a bidirectional association between depression and MetS. These results support early detection and management of depression among patients with MetS and vice versa

Hyperprogressive Disease during Anti-PD-1 (PDCD1) / PD-L1 (CD274) Therapy: A Systematic Review and Meta-Analysis

Hyperprogressive disease (HPD) is a recently acknowledged pattern of rapid tumor progression after the initiation of immune checkpoint inhibitors. HPD has been observed across various types of tumors and has been associated with poor survival. We performed a meta-analysis to identify baseline (i.e., prior to programmed cell death 1 [PD-1, PDCD1] / programmed cell death 1 ligand 1 [PD-L1, CD274] inhibitor therapy) patient factors associated with risks of developing HPD during PD-1/PD-L1 inhibitor therapy. We searched eight databases until 6 June 2019. We calculated the summary odds ratio (OR) and its 95% confidence interval (CI) using the random-effects model and explored between-study heterogeneity and small-study effects. A total of nine articles was eligible (217 HPD cases, 1519 cancer patients) for meta-analysis. There was no standard definition of HPD, and the incidence of HPD ranged from 1 to 30%. We identified twenty-three baseline patient factors, of which five factors were statistically significantly associated with HPD. These were serum lactate dehydrogenase (LDH) above the upper normal limit (OR = 1.89, 95% CI = 1.02-3.49, p = 0.043), more than two metastatic sites (OR = 1.86, 1.34-2.57, p < 0.001), liver metastases (OR = 3.33, 2.07-5.34, p < 0.001), Royal Marsden Hospital prognostic score of 2 or above (OR = 3.33, 1.96-5.66, p < 0.001), and positive PD-L1 expression status that was inversely correlated with HPD (OR = 0.60, 0.36-0.99, p = 0.044). Between-study heterogeneity was low. Evidence of small-study effect was found in one association (PD-L1 expression). Subset analyses of patients with non-small cell lung cancer showed similar results. Future studies are warranted to identify underlying molecular mechanisms and to test their roles as predictive biomarkers of HPD

GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk

Male pattern baldness (MPB) or androgenetic alopecia is one of the most common conditions affecting men, reaching a prevalence of similar to 50% by the age of 50; however, the known genes explain little of the heritability. Here, we present the results of a genome-wide association study including more than 70,000 men, identifying 71 independently replicated loci, of which 30 are novel. These loci explain 38% of the risk, suggesting that MPB is less genetically complex than other complex traits. We show that many of these loci contain genes that are relevant to the pathology and highlight pathways and functions underlying baldness. Finally, despite only showing genome-wide genetic correlation with height, pathway-specific genetic correlations are significant for traits including lifespan and cancer. Our study not only greatly increases the number of MPB loci, illuminating the genetic architecture, but also provides a new approach to disentangling the shared biological pathways underlying complex diseases

Calcium Intake and Risk of Colorectal Cancer According to Tumor-infiltrating T Cells

Calcium intake has been associated with a lower risk of colorectal cancer. Calcium signaling may enhance T-cell proliferation and differentiation, and contribute to T-cell–mediated antitumor immunity. In this prospective cohort study, we investigated the association between calcium intake and colorectal cancer risk according to tumor immunity status to provide additional insights into the role of calcium in colorectal carcinogenesis. The densities of tumor-infiltrating T-cell subsets [CD3+, CD8+, CD45RO (PTPRC)+, or FOXP3+ cell] were assessed using IHC and computer-assisted image analysis in 736 cancer cases that developed among 136,249 individuals in two cohorts. HRs and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression. Total calcium intake was associated with a multivariable HR of 0.55 (comparing ≥1,200 vs. <600 mg/day; 95% CI, 0.36–0.84; Ptrend = 0.002) for CD8+ T-cell–low but not for CD8+ T-cell–high tumors (HR = 1.02; 95% CI, 0.67–1.55; Ptrend = 0.47). Similarly, the corresponding HRs (95% CIs) for calcium for low versus high T-cell–infiltrated tumors were 0.63 (0.42–0.94; Ptrend = 0.01) and 0.89 (0.58–1.35; Ptrend = 0.20) for CD3+; 0.58 (0.39–0.87; Ptrend = 0.006) and 1.04 (0.69–1.58; Ptrend = 0.54) for CD45RO+; and 0.56 (0.36–0.85; Ptrend = 0.006) and 1.10 (0.72–1.67; Ptrend = 0.47) for FOXP3+, although the differences by subtypes defined by T-cell density were not statistically significant. These potential differential associations generally appeared consistent regardless of sex, source of calcium intake, tumor location, and tumor microsatellite instability status. Our findings suggest a possible role of calcium in cancer immunoprevention via modulation of T-cell function

Author Correction:GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk

Male pattern baldness (MPB) or androgenetic alopecia is one of the most common conditions affecting men, reaching a prevalence of similar to 50% by the age of 50; however, the known genes explain little of the heritability. Here, we present the results of a genome-wide association study including more than 70,000 men, identifying 71 independently replicated loci, of which 30 are novel. These loci explain 38% of the risk, suggesting that MPB is less genetically complex than other complex traits. We show that many of these loci contain genes that are relevant to the pathology and highlight pathways and functions underlying baldness. Finally, despite only showing genome-wide genetic correlation with height, pathway-specific genetic correlations are significant for traits including lifespan and cancer. Our study not only greatly increases the number of MPB loci, illuminating the genetic architecture, but also provides a new approach to disentangling the shared biological pathways underlying complex diseases

Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality – a systematic review and dose-response meta-analysis of prospective studies

Background: Questions remain about the strength and shape of the dose-response relationship between fruit and vegetable intake and risk of cardiovascular disease, cancer and mortality, and the effects of specific types of fruit and vegetables. We conducted a systematic review and meta-analysis to clarify these associations. Methods: PubMed and Embase were searched up to 29 September 2016. Prospective studies of fruit and vegetable intake and cardiovascular disease, total cancer and all-cause mortality were included. Summary relative risks (RRs) were calculated using a random effects model, and the mortality burden globally was estimated; 95 studies (142 publications) were included. Results: For fruits and vegetables combined, the summary RR per 200 g/day was 0.92 [95% confidence interval (CI): 0.90–0.94, I2 = 0%, n = 15] for coronary heart disease, 0.84 (95% CI: 0.76–0.92, I2 = 73%, n = 10) for stroke, 0.92 (95% CI: 0.90–0.95, I2 = 31%, n = 13) for cardiovascular disease, 0.97 (95% CI: 0.95–0.99, I2 = 49%, n = 12) for total cancer and 0.90 (95% CI: 0.87–0.93, I2 = 83%, n = 15) for all-cause mortality. Similar associations were observed for fruits and vegetables separately. Reductions in risk were observed up to 800 g/day for all outcomes except cancer (600 g/day). Inverse associations were observed between the intake of apples and pears, citrus fruits, green leafy vegetables, cruciferous vegetables, and salads and cardiovascular disease and all-cause mortality, and between the intake of green-yellow vegetables and cruciferous vegetables and total cancer risk. An estimated 5.6 and 7.8 million premature deaths worldwide in 2013 may be attributable to a fruit and vegetable intake below 500 and 800 g/day, respectively, if the observed associations are causal. Conclusions: Fruit and vegetable intakes were associated with reduced risk of cardiovascular disease, cancer and all-cause mortality. These results support public health recommendations to increase fruit and vegetable intake for the prevention of cardiovascular disease, cancer, and premature mortality

Energy Imbalance and Cancer Risk

Positive energy imbalance occurs when energy intake exceeds energy expenditure. In modern society, increased consumption of caloric-dense food and reduced energy expenditure due to low physical activity and sedentary lifestyle drive positive energy imbalance. Manifested as weight gain, positive energy imbalance is implicated in the development and progression of several cancers. This dissertation focuses on reduced energy expenditure, sedentary behavior and weight gain in relation to cancer risk. In chapter 1, we prospectively evaluated the relationship between physical activity and incident cancers of the digestive system encompassing the digestive tract (mouth, throat, esophagus, stomach, small intestine, and colorectum) and digestive accessory organs (pancreas, gallbladder, and liver) among men in the Health Professionals Follow-Up Study. In men, a higher level of physical activity, regardless of its intensity, was associated with a decreased risk of digestive system cancers, particularly digestive tract cancers. The association was independent of obesity and diabetes. In chapter 2, we examined whether sedentary lifestyle, as indicated by time spent sitting watching TV, has an effect on colorectal cancer risk independent of physical activity. The relationship was prospectively investigated among women in the Nurses’ Health Study and men in the Health Professionals Follow-Up Study. In the combined population of women and men, prolonged sitting watching TV was an independent risk factor for colorectal cancer. The elevated risk associated with prolonged sitting was not completely offset by participation in physical activity. In chapter 3, we assessed the strength and shape of the dose-response relationships between adult weight gain and risk of adiposity-related cancers (e.g., cancers of the breast, endometrium, ovary, prostate, colon, pancreas) using dose-response meta-analysis. Adult weight gain was linearly associated with risk of breast, endometrial, and ovarian cancers among postmenopausal women not using hormone therapy; with risk of colon cancer, particularly among men. Results of this dissertation suggest that increasing the overall amount of physical activity, reducing sedentary time, particularly sitting watching TV, and avoiding adult weight gain should be widely encouraged for the prevention of several major cancers.Nutritio

Milk Intake in Early Life and Later Cancer Risk: A Meta-Analysis

Dairy consumption in adulthood has been demonstrated to influence cancer risk. Although childhood and adolescence represent critical periods of rapid growth, the relationship between milk intake in early life and later cancer risk is unclear. Thus, we examined this relationship by conducting a meta-analysis of the observational studies. PubMed and Embase were searched for relevant articles that were published throughout December 2021. The summary relative risk (RR) and 95% confidence interval (CI) were estimated using the DerSimonian-Laird random-effects model. The summary RR for the highest vs. lowest milk intake was 0.83 (95% CI = 0.69&ndash;1.00; p = 0.05; I2 = 60%; seven studies) for breast cancer, 0.98 (95% CI = 0.72&ndash;1.32; p = 0.88; I2 = 51%; four studies) for prostate cancer, and 0.90 (95% CI = 0.42&ndash;1.93; p = 0.78; I2 = 83%; three studies) for colorectal cancer. No evidence of an association emerged in subgroup analyses of menopausal status, cancer stage, fat content of milk, life stage of milk intake, or study design. Consistent results were observed in the meta-analyses using total dairy intake. In conclusion, milk intake during childhood and adolescence might not be associated with risks of breast, prostate, and colorectal cancer later in life. Given the small number of studies that were included in our meta-analysis, and the high heterogeneity, more studies are warranted for a definitive conclusion