Risk factors for endometrial cancer: An umbrella review of the literature : Risk factors for endometrial cancer

Objective To evaluate the strength and validity of the evidence for the association between adiposity and risk of developing or dying from cancer. Design Umbrella review of systematic reviews and meta-analyses. Data sources PubMed, Embase, Cochrane Database of Systematic Reviews, and manual screening of retrieved references. Eligibility criteria Systematic reviews or meta-analyses of observational studies that evaluated the association between indices of adiposity and risk of developing or dying from cancer. Data synthesis Primary analysis focused on cohort studies exploring associations for continuous measures of adiposity. The evidence was graded into strong, highly suggestive, suggestive, or weak after applying criteria that included the statistical significance of the random effects summary estimate and of the largest study in a meta-analysis, the number of cancer cases, heterogeneity between studies, 95% prediction intervals, small study effects, excess significance bias, and sensitivity analysis with credibility ceilings. Results 204 meta-analyses investigated associations between seven indices of adiposity and developing or dying from 36 primary cancers and their subtypes. Of the 95 meta-analyses that included cohort studies and used a continuous scale to measure adiposity, only 12 (13%) associations for nine cancers were supported by strong evidence. An increase in body mass index was associated with a higher risk of developing oesophageal adenocarcinoma; colon and rectal cancer in men; biliary tract system and pancreatic cancer; endometrial cancer in premenopausal women; kidney cancer; and multiple myeloma. Weight gain and waist to hip circumference ratio were associated with higher risks of postmenopausal breast cancer in women who have never used hormone replacement therapy and endometrial cancer, respectively. The increase in the risk of developing cancer for every 5 kg/m2 increase in body mass index ranged from 9% (relative risk 1.09, 95% confidence interval 1.06 to 1.13) for rectal cancer among men to 56% (1.56, 1.34 to 1.81) for biliary tract system cancer. The risk of postmenopausal breast cancer among women who have never used HRT increased by 11% for each 5 kg of weight gain in adulthood (1.11, 1.09 to 1.13), and the risk of endometrial cancer increased by 21% for each 0.1 increase in waist to hip ratio (1.21, 1.13 to 1.29). Five additional associations were supported by strong evidence when categorical measures of adiposity were included: weight gain with colorectal cancer; body mass index with gallbladder, gastric cardia, and ovarian cancer; and multiple myeloma mortality. Conclusions Although the association of adiposity with cancer risk has been extensively studied, associations for only 11 cancers (oesophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney) were supported by strong evidence. Other associations could be genuine, but substantial uncertainty remains. Obesity is becoming one of the biggest problems in public health; evidence on the strength of the associated risks may allow finer selection of those at higher risk of cancer, who could be targeted for personalised prevention strategies.

Recent advances in Bayesian hypothesis testing have led to the development of uniformly most powerful Bayesian tests, which represent an objective, default class of Bayesian hypothesis tests that have the same rejection regions as classical significance tests. Based on the correspondence between these two classes of tests, it is possible to equate the size of classical hypothesis tests with evidence thresholds in Bayesian tests, and to equate P values with Bayes factors. An examination of these connections suggest that recent concerns over the lack of reproducibility of scientific studies can be attributed largely to the conduct of significance tests at unjustifiably high levels of significance. To correct this problem, evidence thresholds required for the declaration of a significant finding should be increased to 25-50:1, and to 100-200:1 for the declaration of a highly significant finding. In terms of classical hypothesis tests, these evidence standards mandate the conduct of tests at the 0.005 or 0.001 level of significance.

Sedentary behavior (prolonged sitting or reclining characterized by low energy expenditure) is associated with adverse cardiometabolic profiles and premature cardiovascular mortality. Less is known for cancer risk. The purpose of this review is to evaluate the research on sedentary behavior and cancer, to summarize possible biological pathways that may underlie these associations, and to propose an agenda for future research. Articles pertaining to sedentary behavior and (a) cancer outcomes and (b) mechanisms that may underlie the associations between sedentary behavior and cancer were retrieved using Ovid and Web of Science databases. The literature review identified 18 articles pertaining to sedentary behavior and cancer risk, or to sedentary behavior and health outcomes in cancer survivors. Ten of these studies found statistically significant, positive associations between sedentary behavior and cancer outcomes. Sedentary behavior was associated with increased colorectal, endometrial, ovarian, and prostate cancer risk; cancer mortality in women; and weight gain in colorectal cancer survivors. The review of the literature on sedentary behavior and biological pathways supported the hypothesized role of adiposity and metabolic dysfunction as mechanisms operant in the association between sedentary behavior and cancer. Sedentary behavior is ubiquitous in contemporary society; its role in relation to cancer risk should be a research priority. Improving conceptualization and measurement of sedentary behavior is necessary to enhance validity of future work. Reducing sedentary behavior may be a viable new cancer control strategy. ©2010 AACR.