Excess adiposity is a risk factor for several cancers of the gastrointestinal system, specifically oesophageal adenocarcinoma and colorectal, small intestine, pancreatic, liver, gallbladder and ...stomach cancers. With the increasing prevalence of obesity in nearly all regions of the world, this relationship could represent a growing source of cancers of the digestive system. Experimental and molecular epidemiological studies indicate important roles for alterations in insulin signalling, adipose tissue-derived inflammation and sex hormone pathways in mediating the association between adiposity and gastrointestinal cancer. The intestinal microbiome, gut hormones and non alcoholic fatty liver disease (NAFLD) also have possible roles. However, important gaps remain in our knowledge. For instance, our understanding of how adiposity throughout the life course is related to the risk of gastrointestinal cancer development and of how obesity influences gastrointestinal cancer prognosis and survival is limited. Nonetheless, the increasing use of state-of-the-art analytical methods (such as omics technologies, Mendelian randomization and MRI) in large-scale epidemiological studies offers exciting opportunities to advance our understanding of the complex relationship between adiposity and gastrointestinal cancers. Here, we examine the epidemiology of associations between obesity and gastrointestinal cancer, explore potential mechanisms underlying these relationships and highlight important unanswered research questions.
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.
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.
Diabetes and high body-mass index (BMI) are associated with increased risk of several cancers, and are increasing in prevalence in most countries. We estimated the cancer incidence attributable to ...diabetes and high BMI as individual risk factors and in combination, by country and sex.
We estimated population attributable fractions for 12 cancers by age and sex for 175 countries in 2012. We defined high BMI as a BMI greater than or equal to 25 kg/m2. We used comprehensive prevalence estimates of diabetes and BMI categories in 2002, assuming a 10-year lag between exposure to diabetes or high BMI and incidence of cancer, combined with relative risks from published estimates, to quantify contribution of diabetes and high BMI to site-specific cancers, individually and combined as independent risk factors and in a conservative scenario in which we assumed full overlap of risk of diabetes and high BMI. We then used GLOBOCAN cancer incidence data to estimate the number of cancer cases attributable to the two risk factors. We also estimated the number of cancer cases in 2012 that were attributable to increases in the prevalence of diabetes and high BMI from 1980 to 2002. All analyses were done at individual country level and grouped by region for reporting.
We estimated that 5·7% of all incident cancers in 2012 were attributable to the combined effects of diabetes and high BMI as independent risk factors, corresponding to 804 100 new cases. 187 600 (24·5%) of 766 000 cases of liver cancer and 121 700 (38·4%) of 317 000 cases of endometrial cancer were attributable to these risk factors. In the conservative scenario, about 4·5% (629 000 new cases) of all incident cancers assessed were attributable to diabetes and high BMI combined. Individually, high BMI (544 300 cases) was responsible for almost twice as many cancer cases as diabetes (293 300 cases). 25·8% of diabetes-related cancers (equating to 75 600 new cases) and 31·9% of high BMI-related cancers (174 040 new cases) were attributable to increases in the prevalence of these risk factors from 1980 to 2002.
A substantial number of cancer cases are attributable to diabetes and high BMI. As the prevalence of these cancer risk factors increases, clinical and public health efforts should focus on identifying optimal preventive and screening measures for whole populations and individual patients.
NIHR and Wellcome Trust.
Abstract
Background
Epidemiological studies have found that menopausal hormone therapy (MHT) use is associated with an increased ovarian cancer risk. However, whether different MHT types confer the ...same level of risk is unclear. We estimated the associations between different MHT types and the risk of ovarian cancer in a prospective cohort.
Methods
The study population included 75 606 postmenopausal women from the E3N cohort. Exposure to MHT was identified from self-reports in biennial questionnaires between 1992 and 2004 and from drug claim data matched to the cohort between 2004 and 2014. Hazard ratios and 95% confidence intervals (CIs) of ovarian cancer were estimated using multivariable Cox proportional hazards models with MHT as a time-varying exposure. Tests of statistical significance were 2-sided.
Results
Over an average 15.3 years follow-up, 416 ovarian cancers were diagnosed. Hazard ratios of ovarian cancer associated with ever use of estrogens combined with progesterone or dydrogesterone and ever use of estrogens combined with other progestagen were equal to 1.28 (95% CI = 1.04 to 1.57) and 0.81 (95% CI = 0.65 to 1.00), respectively (Phomogeneity = .003), compared with never use. The hazard ratio for unopposed estrogen use was 1.09 (95% CI = 0.82 to 1.46). We found no trend according to duration of use or time since last use except for estrogens combined with progesterone or dydrogesterone, which showed decreasing risk with increasing time since last use.
Conclusion
Different MHT types may impact ovarian cancer risk differentially. The possibility that MHT containing progestagens other than progesterone or dydrogesterone may confer some protection should be evaluated in other epidemiological studies.
Alcohol is a major risk factor for oesophageal squamous cell carcinoma (OSCC), the most prevalent histological subtype of oesophageal cancer (OC) worldwide. The metabolism of alcohol is regulated by ...specific enzymes whose activity and expression is influenced by genetic polymorphisms. We conducted a systematic review of current epidemiological evidence of the relationship between alcohol intake and OC risk, including the role of tobacco smoking and functional polymorphisms of alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs). Potential biological mechanisms underlying oesophageal carcinogenesis are also discussed. Frequency and intensity of alcohol intake have been consistently associated with an increased risk of OSCC in regions with low and high incidence of the disease. The highest risk was reported among tobacco smokers, whereas the association between alcohol and OSCC risk was weak in the absence of tobacco use. The ADH1B, ADH1C and ALDH2 gene polymorphisms influence the risk of OSCC through modulation of acetaldehyde metabolism and propensity to alcohol intake. These functional variants may be suitable proxies of alcohol exposure for use in Mendelian randomization studies if complemented by reported alcohol intake data. Recent epidemiological and experimental studies investigating the role of alcohol consumption in OC development have implicated the microbiome as a new promising avenue for research, which entail novel potential mechanisms of alcohol-related oesophageal carcinogenesis. Microbial communities associated with alcohol consumption might be used as biomarkers to raise the potential of intervening among susceptible individuals.
Colorectal cancer (CRC) incidence changes with time and by variations in diet and lifestyle, as evidenced historically by migrant studies and recently by extensive epidemiologic evidence. The ...worldwide heterogeneity in CRC incidence is strongly suggestive of etiological involvement of environmental exposures, particularly lifestyle and diet. It is established that physical inactivity, obesity and some dietary factors (red/processed meats, alcohol) are positively associated with CRC, while healthy lifestyle habits show inverse associations. Mechanistic evidence shows that lifestyle and dietary components that contribute to energy excess are linked with increased CRC via metabolic dysfunction, inflammation, oxidative stress, bacterial dysbiosis and breakdown of gut barrier integrity while the reverse is apparent for components associated with decreased risk. This chapter will review the available evidence on lifestyle and dietary factors in CRC etiology and their underlying mechanisms in CRC development. This short review will also touch upon available information on potential gene-environment interactions, molecular sub-types of CRC and anatomical sub-sites within the colorectum.
In recent years, there has been an increasing interest in investigating the carcinogenicity of mycotoxins in humans. This systematic review aims to provide an overview of data linking exposure to ...different mycotoxins with human cancer risk. Publications (2019 and earlier) of case–control or longitudinal cohort studies were identified in PubMed and EMBASE. These articles were then screened by independent reviewers and their quality was assessed according to the Newcastle–Ottawa scale. Animal, cross‐sectional, and molecular studies satisfied criteria for exclusion. In total, 14 articles were included: 13 case–control studies and 1 longitudinal cohort study. Included articles focused on associations of mycotoxin exposure with primary liver, breast, and cervical cancer. Overall, a positive association between the consumption of aflatoxin‐contaminated foods and primary liver cancer risk was verified. Two case–control studies in Africa investigated the relationship between zearalenone and its metabolites and breast cancer risk, though conflicting results were reported. Two case–control studies investigated the association between hepatocellular carcinoma and fumonisin B1 exposure, but no significant associations were observed. This systematic review incorporates several clear observations of dose‐dependent associations between aflatoxins and liver cancer risk, in keeping with IARC Monograph conclusions. Only few human epidemiological studies investigated the associations between mycotoxin exposures and cancer risk. To close this gap, more in‐depth research is needed to unravel evidence for other common mycotoxins, such as deoxynivalenol and ochratoxin A. The link between mycotoxin exposures and cancer risk has mainly been established in experimental studies, and needs to be confirmed in human epidemiological studies to support the evidence‐based public health strategies.
Type 2 diabetes mellitus (T2DM) has been associated with an increased risk of developing several common cancers, but it is unclear whether this association is causal. We aimed to summarize the ...evidence on T2DM and cancer and evaluate the validity of associations from both observational and Mendelian randomization (MR) studies.
We performed an umbrella review of the evidence across meta-analyses of observational studies that examined associations of T2DM with risk of developing or dying from site-specific cancers, and MR studies that explored the potential causal association of T2DM and associated biomarkers with cancer risk.
We identified eligible observational meta-analyses that assessed associations between T2DM and cancer incidence for 18 cancer sites, cancer mortality for seven sites, and cancer incidence or mortality for four sites. Positive associations between T2DM and six cancers reached strong or highly suggestive evidence. We found eight MR studies assessing the association of genetically predicted T2DM and seven and eight studies assessing the association of genetically predicted fasting insulin or fasting glucose concentrations, respectively, upon site-specific cancers. Positive associations were found between genetically predicted T2DM and fasting insulin and risk of six cancers. There was no association between genetically predicted fasting plasma glucose and cancer except for squamous cell lung carcinoma.
We found robust observational evidence for the association between T2DM and colorectal, hepatocellular, gallbladder, breast, endometrial, and pancreatic cancers.
Potential causal associations were identified for genetically predicted T2DM and fasting insulin concentrations and risk of endometrial, pancreas, kidney, breast, lung, and cervical cancers.
Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been ...scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases.
In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs.
During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles.
Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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