Although many risk factors could have causal association with endometrial cancer, they are also prone to residual confounding or other biases which could lead to over- or underestimation. This umbrella review evaluates the strength and validity of evidence pertaining risk factors for endometrial cancer. Systematic reviews or meta-analyses of observational studies evaluating the association between non-genetic risk factors and risk of developing or dying from endometrial cancer were identified from inception to April 2018 using PubMed, the Cochrane database and manual reference screening. Evidence was graded strong, highly suggestive, suggestive or weak based on statistical significance of random-effects summary estimate, largest study included, number of cases, between-study heterogeneity, 95% prediction intervals, small study effects, excess significance bias and sensitivity analysis with credibility ceilings. We identified 171 meta-analyses investigating associations between 53 risk factors and endometrial cancer incidence and mortality. Risk factors were categorised: anthropometric indices, dietary intake, physical activity, medical conditions, hormonal therapy use, biochemical markers, gynaecological history and smoking. Of 127 meta-analyses including cohort studies, three associations were graded with strong evidence. Body mass index and waist-to-hip ratio were associated with increased cancer risk in premenopausal women (RR per 5 kg/m2 1.49; CI 1.39-1.61) and for total endometrial cancer (RR per 0.1unit 1.21; CI 1.13-1.29), respectively. Parity reduced risk of disease (RR 0.66, CI 0.60-0.74). Of many proposed risk factors, only three had strong association without hints of bias. Identification of genuine risk factors associated with endometrial cancer may assist in developing targeted prevention strategies for women at high risk. This article is protected by copyright. All rights reserved.
The epidemiology of multiple myeloma (MM) is an increasingly investigated field, with many controversies. This systematic review aims to synthesize meta-analyses examining risk factors for MM so as to provide a comprehensive, parsimonious summary of the current evidence. Eligible meta-analyses were sought in PubMed adopting a predefined algorithm, without any restriction of publication language; end-of-search date was October 10, 2014. The selection of eligible studies and data extraction were performed by working in pairs, independently and blindly to each other; in case of disagreement, consensus with the whole team was reached. Among the 22 ultimately included meta-analyses, 9 examined occupational factors, 4 assessed aspects of lifestyle (smoking, alcohol, body mass index), 5 evaluated the presence of other diseases, and 4 addressed genetic factors as potential risk factors of MM. A vast compendium of significant associations arose, including farming, occupation as a firefighter, occupation as a hairdresser, exposures to chemicals or pesticides, overweight and obesity, patterns of alcohol intake, pernicious anemia, ankylosing spondylitis, gene promoter methylation, and polymorphisms. In conclusion, MM is a multifactorial disease, encompassing a wide variety of risk factors that span numerous life aspects. Further accumulation of evidence through meta-analyses is anticipated in this rapidly growing field.
OBJECTIVES: To summarise the evidence and evaluate the validity of the associations between type 2 diabetes and the risk of developing or dying from cancer.
DESIGN: An umbrella review of the evidence across meta-analyses of observational studies of type 2 diabetes with risk of developing or dying from any cancer.
DATA SOURCES: PubMed, Embase, Cochrane database of systematic reviews, and manual screening of references.
ELIGIBILITY CRITERIA: Meta-analyses or systematic reviews of observational studies in humans that examined the association between type 2 diabetes and risk of developing or dying from cancer.
RESULTS: Eligible meta-analyses assessed associations between type 2 diabetes and risk of developing cancer in 20 sites and mortality for seven cancer sites. The summary random effects estimates were significant at P=0.05 in 20 meta-analyses (74%); and all reported increased risks of developing cancer for participants with versus without diabetes. Of the 27 meta-analyses, eventually only seven (26%) compiled evidence on more than 1000 cases, had significant summary associations at P ≤ 0.001 for both random and fixed effects calculations, and had neither evidence of small study effects nor evidence for excess significance. Of those, only six (22%) did not have substantial heterogeneity (I(2)>75%), pertaining to associations between type 2 diabetes and risk of developing breast, cholangiocarcinoma (both intrahepatic and extrahepatic), colorectal, endometrial, and gallbladder cancer. The 95% prediction intervals excluded the null value for four of these associations (breast, intrahepatic cholangiocarcinoma, colorectal, and endometrial cancer).
CONCLUSIONS: Though type 2 diabetes has been extensively studied in relation to risk of developing cancer and cancer mortality and strong claims of significance exist for most of the studied associations, only a minority of these associations have robust supporting evidence without hints of bias.
Although many risk factors could have causal association with endometrial cancer, they are also prone to residual confounding or other biases which could lead to over- or underestimation. This umbrella review evaluates the strength and validity of evidence pertaining risk factors for endometrial cancer. Systematic reviews or meta-analyses of observational studies evaluating the association between non-genetic risk factors and risk of developing or dying from endometrial cancer were identified from inception to April 2018 using PubMed, the Cochrane database and manual reference screening. Evidence was graded strong, highly suggestive, suggestive or weak based on statistical significance of random-effects summary estimate, largest study included, number of cases, between-study heterogeneity, 95% prediction intervals, small study effects, excess significance bias and sensitivity analysis with credibility ceilings. We identified 171 meta-analyses investigating associations between 53 risk factors and endometrial cancer incidence and mortality. Risk factors were categorised: anthropometric indices, dietary intake, physical activity, medical conditions, hormonal therapy use, biochemical markers, gynaecological history and smoking. Of 127 meta-analyses including cohort studies, three associations were graded with strong evidence. Body mass index and waist-to-hip ratio were associated with increased cancer risk in premenopausal women (RR per 5 kg/m2 1.49; CI 1.39-1.61) and for total endometrial cancer (RR per 0.1unit 1.21; CI 1.13-1.29), respectively. Parity reduced risk of disease (RR 0.66, CI 0.60-0.74). Of many proposed risk factors, only three had strong association without hints of bias. Identification of genuine risk factors associated with endometrial cancer may assist in developing targeted prevention strategies for women at high risk. This article is protected by copyright. All rights reserved.
