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Abstract

The incidence of adenocarcinoma of the oesophagus in British women is among the highest in the world. To investigate its aetiology, we conducted a multi-centre, population based case-control study in four regions in England and Scotland. We included 74 incident cases in women with histologically confirmed diagnoses of adenocarcinoma of the oesophagus, and 74 female controls matched by age and general practice. High body mass index (BMI) around the age of 20 years (highest vs lowest quartile, adjusted odds ratio (OR) = 6.04, 95% confidence interval (CI) 1.28-28.52) and low consumption of fruit (highest vs lowest quartile, adjusted OR = 0.08, 95% CI 0.01-0.49) were associated with increases in risk. Breastfeeding by women was associated with reduced risk of their subsequently developing this cancer (ever vs never, adjusted OR = 0.41, 95% CI 0.20-0.82) and there was a significant dose-response effect with total duration of breastfeeding. The summary population attributable risk from these three factors was 96% (90% if breastfeeding is excluded). We conclude that high BMI in early adulthood and low consumption of fruit are important risk factors for adenocarcinoma of the oesophagus. Breastfeeding may confer a protective effect but this needs confirmation. This cancer is a largely preventable disease in women.

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... and obese if it is ≥30.0. With regard to weight control, several case-control and cross-sectional studies have demonstrated the association between a high BMI and the risk of EAC [38][39][40]42,53,57,63,75,80,81,86,88,93,95,103]. The studies included in our systematic review found a statistically significant higher risk of EAC in obese patients. ...
... In the EPIC study, the authors also showed a negative, although not significant, association between vegetable intake leafy vegetable intake and EAC risk [108]. A possible protective role of fruit in reducing EAC risk has been confirmed in several studies [32,38,129], with a linear relation [38], and in particular for citrus fruits [129]. However, three studies [106,108,129] found a non-significant inverse association between fruit intake and EAC risk. ...
... In the EPIC study, the authors also showed a negative, although not significant, association between vegetable intake leafy vegetable intake and EAC risk [108]. A possible protective role of fruit in reducing EAC risk has been confirmed in several studies [32,38,129], with a linear relation [38], and in particular for citrus fruits [129]. However, three studies [106,108,129] found a non-significant inverse association between fruit intake and EAC risk. ...
Article
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One of the most notable changes in the epidemiology of esophageal cancer (EC) is the rising incidence and prevalence of esophageal adenocarcinoma (EAC) in developed countries. The aim of this systematic review was to collect and summarize all the available evidence regarding lifestyle, diet, and EAC risk. We searched the PubMed and Scopus databases in January 2021 for studies providing information about lifestyle, diet, WCRF/AICR recommendations, and EAC risk; published in English; without a time filter. The Newcastle-Ottawa Scale was used to assess risk of bias. The results are stratified by risk factor. A total of 106 publications were included. Half of the case-control studies were judged as high quality, whilst practically all cohort studies were judged as high quality. Body mass index and waist circumference were associated with increased EAC risk. Physical activity did not appear to have a significant direct role in EAC risk. A diet rich in fruit, vegetables, and whole grains appeared to be more protective than a Western diet. Alcohol does not seem to be related to EAC, whereas smokers, particularly heavy smokers, have an increased risk of EAC. Prevention remains the best option to avert EAC. Comprehensible and easy to follow recommendations should be provided to all subjects. Protocol ID number: CRD-42021228762, no funds received.
... So far neither amount nor frequency of consumption of vegetables that would reduce the risk of oesophageal cancer, have been established (7)(8)(9)(10). Some case-control studies indicate that consumption of vegetables more than once a week may reduce the incidence of oesophageal cancer (11)(12)(13)(14)(15). ...
... Six case-control studies found 50-60% risk reduction of oesophageal cancer. Studies that did not find a protective effect of vegetables enriched diet were conducted in USA (11), England (12), Italy (13), Argentina (14), Uruguay and Eastern Europe (21). Meta-analysis of subjects of the analyzed studies included a total of 1030 patients with oesophageal cancer (tab. 1) and demonstrated that consumption of vegetables more often than once a week reduced risk of oesophageal cancer by 48% (RR 0.52; 95% CI 0.38-0.71) ...
... Dotychczas nie określono ilości i częstości spożywania warzyw, które miałoby działanie zmniejszające ryzyko zachorowania na raka przełyku (7)(8)(9)(10). Niektóre z badań klinicznokontrolnych wskazują, że częstość spożywania warzyw większa niż raz w tygodniu może obniżyć częstość zachorowania na raka przełyku (11)(12)(13)(14)(15). ...
Article
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Oesophagus is common primary localization of digestive system cancer. Recent analyses suggest the role of vegetarian food in reduction of cancer risk. The role of vegetables intake in oesophageal cancer prevention still needs to be proved. Objective. The estimation of the role of vegetables intake in oesophageal cancer risk based on published case-control studies using meta-analysis methods. Methods. The selected literature published till 2009 from MEDLINE, PubMed, Scopus, Embase, CancerLit, Google Scholar and Cochrane Library databases were included into meta-analysis. The following search terms, key words and text phrases were used: esophageal cancer, cancer risk, oesophageal cancer risk, oesophageal neoplasm; oesophageal neoplasm risk, diet, dietary habits, vegetables and life style. Articles investigating vegetables intake were reviewed and selected for further analysis. Results. Twelve studies have fulfilled the established criteria. The meta-analysis has confirmed the protective effect of vegetables against oesophageal cancer development. The vegetables intake, more frequent than once per week, reduce oesophageal cancer risk (relative risk 0.52; 95% CI 0.38-0.71). The declared intake more frequent than once daily was connected with reduction of cancer development about of 57% (relative risk 0.43; 95% CI 0.32-0.58). The dose-dependent manner of vegetables intake was observed against oesophageal cancer development. Conclusion. The vegetables intake is associated with reduced risk of developing an oesophageal cancer. The total reduction of oesophageal cancer risk is associated with frequency of vegetables intake in the diet.
... Obesity has been previously identified as a risk factor for EAC, [7][8][9][10][11] which is known to predispose patients to increased gastroesophageal reflux due to anatomic factors such as increased abdominal and intraperitoneal adiposity and hiatal hernia formation. Obesity is also known to mediate carcinogenesis via insulin resistance, inflammation and oxidative stress, and production of fat-associated hormones (adipokines). ...
... 26 In a study of British women with EAC, a history of diabetes was associated with an elevated risk of borderline statistical significance. 8 A meta-analysis of three case-control studies demonstrated that diabetes imparted a summary of relative risk of 2.12 (95% CI 1.01-4.46) for esophageal adenocarcinoma. ...
Article
In the past 30 years, the incidence of esophageal adenocarcinoma (EAC) has increased more rapidly than any other cancer in the United States. The prevalence of obesity and diabetes mellitus has drastically increased as well. We explored the potential association between obesity, diabetes mellitus, and EAC. By means of retrospective interrogation of an administrative database from fiscal year 2005-2009, we identified two cohorts. The cancer cohort was defined as patients with adenocarcinoma of the distal esophagus or gastric cardia. The comparison cohort contained patients with gastroesophageal reflux disorder (GERD; diagnosis coupled with a procedure code for fundoplication). Patient data, including demographic measures, diagnoses of obesity, diabetes mellitus, dyslipidemia, alcohol abuse, and nicotine dependence were examined. A logistic regression model identified risk factors for development of EAC. The sample included 2,836 patients identified as having either EAC (1,704) or fundoplication with GERD (1,132). Although slightly higher percentages of the benign cohort were obese, the cancer cohort had more diabetics (30.8% vs. 14.8%; chi-square = 94.5; P < 0.0001). In a logistic regression analysis adjusting for comorbidity and lifestyle factors, diagnosis of diabetes mellitus was significantly associated with esophageal cancer as opposed to GERD without cancer (OR = 2.2; 95% confidence interval [CI] 1.7-2.8). Nicotine dependence was also identified as a risk factor (OR = 1.7; 95% CI 1.4-2.0). We identified a potential association between diabetes mellitus and adenocarcinoma of the esophagus or gastric cardia. This association appears to be independent of obesity. Additionally, nicotine dependence was identified as a risk factor for EAC.
... The BEACON consortium was formed in 2005 by an international group of investigators. [21][22][23][24][25][26][27][28][29][30][31][32][33] Consortium data consist of population-based case-control and cohort studies of EA, EGJA and Barrett's esophagus. The large total amount of consortium data enables the conduct of etiological studies of these conditions with excellent statistical power. ...
... 27 Details about source populations, case definitions, recruitment procedures, participants and study designs have been reported previously. [21][22][23][24][25][26][27][28][29][30][31][32][33][34] The main outcomes of interest were age-specific groups of EA and EGJA patients; particularly early-onset disease (<50 years) given that risk factor profiles for this rarer group are poorly understood. Subjects were limited to those of white non-Hispanic ancestry, because of relatively small numbers of non-white or Hispanic patients (26 black, 89 Hispanic, 42 other race or ethnic groups). ...
Article
Esophageal (EA) and esophagogastric junction (EGJA) adenocarcinoma have been steadily increasing in frequency in younger people, however the etiology of these cancers is poorly understood. We therefore investigated associations of body- mass index (BMI), cigarette smoking, alcohol consumption, gastroesophageal reflux, and use of non-steroidal anti-inflammatory drugs (NSAIDs) in relation to age-specific risks of EA and EGJA. We pooled individual participant data from eight population-based, case-control studies within the international Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). The analysis included 1,363 EA patients, 1,472 EGJA patients, and 5,728 control participants. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for age-specific (<50, 50-59, 60-69, ≥70 years) cancer outcomes, as well as interactions by age. BMI, smoking status and pack-years, recurrent gastroesophageal reflux, and frequency of gastroesophageal reflux were positively associated with EA and EGJA in each age group. Early-onset EA (<50 years) had stronger associations with recurrent gastroesophageal reflux (OR=8.06, 95%CI: 4.52, 14.37; Peffect modification =0.01) and BMI (ORBMI ≥30 vs. <25 =4.19, 95%CI: 2.23, 7.87; Peffect modification =0.04), relative to older age groups. In contrast, inverse associations of NSAID use were strongest in the oldest age group (≥70 years), although this apparent difference was not statistically significant. Age-specific associations with EGJA showed similar, but slightly weaker patterns and no statistically significant differences by age were observed. Our study provides evidence that associations between obesity and gastroesophageal reflux are stronger among earlier onset EA cancers. This article is protected by copyright. All rights reserved. © 2015 UICC.
... After a literature search and screening, a total of 14 studies were included in the final analysis (La Vecchia et al., 1993;Cheng et al., 2000;Gallus et al., 2001;Anderson et al., 2007;Corley et al., 2008;Whiteman et al., 2008;Freedman et al., 2010;Bodelon et al., 2011;Chen et al., 2011;Yu et al., 2011;Islami et al., 2013;Lu and Lagergren, 2012;Green et al., 2012aGreen et al., , 2012b. The selection process for the studies included in the metaanalysis is presented in Fig. 1. ...
... Previous evidence has found that hormonal changes occur during lactation (Thomas, 1984). A case-control study (Cheng et al., 2000) also indicated a dose-dependent decreased risk of EA among those who ever breastfed compared with those who never did. Although it is not enough to assert that breastfeeding is a protective factor for oesophageal cancer, this could provide an avenue for further study. ...
Article
To further evaluate the association between reproductive events and the development of oesophageal cancer, we searched relevant studies using electronic databases (PubMed, ISI Web of Science). Study-specific relative risks with corresponding 95% confidence intervals (CI) in all analyses were used and multiple summary relative risk (SRR) estimates were calculated. We carried out subgroup analyses and used meta-regression techniques to explore potential sources of heterogeneity. Sensitivity analysis was carried out to identify whether pooled results were influenced by individual studies and publication bias was assessed by Begg's funnel plots and the Egger regression asymmetry test. Fourteen studies were eligible for inclusion in the meta-analysis, summarizing a total of 3816 oesophageal cancer cases. We found that age at menopause (SRR=0.70; 95% CI: 0.51-0.95) and hormone replacement therapy (SRR=0.67; 95% CI: 0.56-0.81) had an association with a decreased risk of oesophageal cancer. A similar result was obtained for parity (SRR=0.79; 95% CI: 0.71-0.89) and ever breastfeeding (SRR=0.65; 95% CI: 0.43-0.97). In contrast, postmenopausal status was associated with increased risk (SRR=1.65; 95% CI: 1.28-2.14). No statistically significant link was found with other exposures. Our meta-analysis supports the substantial influence of reproductive factors, which could be causally linked to oesophageal cancer.
... Similarly, other putative chemopreventive agents have not yet demonstrated effectiveness, and thus they should not be administered routinely. However, ASA and NSAIDs have shown how the potential of inhibiting several pathways is crucial in oncogenesis, while some epidemiological studies revealed the chemo-preventive effect of ASA in the transition from BE to EAC [70][71][72][73][74][75][76][77][78][79][80]. The use of these chemo-preventive agents, due to their well-known adverse effects such as cerebral and GI hemorrhage, is not justified also considering that the estimated risk of progression in patients with non-dysplastic BE is low (0.1-0.5%/year). ...
... Observational [71][72][73][74][75][76][77][78][79] Meta-analysis [80] Statistical pooling showed a protective association between any use of aspirin/NSAID and esophageal cancer (OR 0.57; 95% CI 0.47-0.71). Both intermittent (OR 0.82; CI, 0.67-0.99) ...
Article
Full-text available
In the last 30 years, we have witnessed a rapid increase in the incidence and prevalence of esophageal cancer in many countries around the word. However, despite advancements in diagnostic technologies, the early detection of this cancer is rare, and its prognosis remains poor, with only about 20% of these patients surviving for 5 years. The two major forms are the esophageal squamous cell carcinoma (ESCC), which is particularly frequent in the so-called Asian belt, and the esophageal adenocarcinoma (EAC), which prevails in Western populations. This review provides a summary of the epidemiological features and risk factors associated with these tumors. Moreover, a major focus is posed on reporting and highlighting the various preventing strategies proposed by the most important international scientific societies, particularly in high-risk populations, with the final aim of detecting these lesions as early as possible and therefore favoring their definite cure. Indeed, we have conducted analysis with attention to the current primary, secondary and tertiary prevention guidelines in both ESCC and EAC, attempting to emphasize unresolved research and clinical problems related to these topics in order to improve our diagnostic strategies and management.
... When we limited the meta-analysis to the 6 studies specified for the subtypes of EAC, [1,24,25,27,34,35] we found a positive association between EAC and diabetes (RR = 1.43, 95% CI: 1.35-1.51, P < .001) ...
... [47] Each of these may enhance difficulty to assess EC risk in DM patients, so deep-going researches based on these confounding factors are needed. In this meta-analysis, there were 6 studies presenting results specific for EAC, [1,24,25,27,34,35] which showed a significant positive correlation between diabetes and EAC risk. However, the results need to be interpreted with caution because of several reasons: The incidence of diabetes among controls was different from prevailing population estimates for each study; Five studies adjusted for GERD, which are the most important risk for EAC. ...
Article
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Background Many studies have showed that diabetes mellitus (DM) might be a risk factor for certain types of cancers. However, there are still inconsistent results on the effects of DM on the risk of esophageal cancer (EC). The objective of this study is to investigate the association and to quantify the correlation between DM and EC by a meta-analysis. Methods The initial search identified 339 articles. Those publications that did not report the exact number of EC cases were removed. Finally, 13 meaningful studies were extracted from the databases of PubMed, MEDLINE, and Web of Science. All pooled analyses of risk ratios (RRs) and 95% confidence intervals (CIs) were assessed by a random-effect or fixed-effect model. Subgroup analysis was implemented on the basis of the sex or ethnicity. I² value was used to assess heterogeneity, and funnel plot analysis was for publication bias. Results The result showed that there was a positive correlation between type 2 diabetes mellitus (T2DM) and EC risk (RR = 1.28, 95% CI: 1.12–1.47, P < .001). Subgroup analysis based on gender showed that male was an important risk factor for EC (RR = 1.53, 95% CI: 1.44–1.62, P < .001), but female was not (RR = 1.23, 95% CI: 0.41–3.69, P = .71). In addition, subgroup analysis based on ethnicity showed that DM was significantly correlated to EC in North America subjects (RR = 1.39, 95% CI: 1.31–1.47, P < .001), and in Europe subjects (RR = 1.37, 95% CI: 1.02–1.83, P = .04), whereas no correlation was found in Asian subjects (RR = 0.98, 95% CI: 0.50–1.95, P = .96). Furthermore, DM had a correlation to an increased risk of esophageal adenocarcinoma (EAC) (RR = 1.43, 95% CI: 1.35–1.51, P < .001). Conclusion This meta-analysis indicates that DM is positively correlated to EC. However, the results should be interpreted with caution because of the limitations on potential clinical confounding factors in each study included in this meta-analysis.
... Obesity has been previously identified as a risk factor for EAC, [7][8][9][10][11] which is known to predispose patients to increased gastroesophageal reflux due to anatomic factors such as increased abdominal and intraperitoneal adiposity and hiatal hernia formation. Obesity is also known to mediate carcinogenesis via insulin resistance, inflammation and oxidative stress, and production of fat-associated hormones (adipokines). ...
... 26 In a study of British women with EAC, a history of diabetes was associated with an elevated risk of borderline statistical significance. 8 A meta-analysis of three case-control studies demonstrated that diabetes imparted a summary of relative risk of 2.12 (95% CI 1.01-4.46) for esophageal adenocarcinoma. ...
Article
In the past 30 years, the incidence of esophageal adenocarcinoma (EAC) has increased more rapidly than any other cancer in the United States. The prevalence of obesity and diabetes mellitus has drastically increased as well. We explored the potential association between obesity, diabetes mellitus, and EAC. By means of retrospective interrogation of an administrative database from fiscal year 2005-2009, we identified two cohorts. The cancer cohort was defined as patients with adenocarcinoma of the distal esophagus or gastric cardia. The comparison cohort contained patients with gastroesophageal reflux disorder (GERD; diagnosis coupled with a procedure code for fundoplication). Patient data, including demographic measures, diagnoses of obesity, diabetes mellitus, dyslipidemia, alcohol abuse, and nicotine dependence were examined. A logistic regression model identified risk factors for development of EAC. The sample included 2,836 patients identified as having either EAC (1,704) or fundoplication with GERD (1,132). Although slightly higher percentages of the benign cohort were obese, the cancer cohort had more diabetics (30.8% vs. 14.8%; chi-square = 94.5; P < 0.0001). In a logistic regression analysis adjusting for comorbidity and lifestyle factors, diagnosis of diabetes mellitus was significantly associated with esophageal cancer as opposed to GERD without cancer (OR = 2.2; 95% confidence interval [CI] 1.7-2.8). Nicotine dependence was also identified as a risk factor (OR = 1.7; 95% CI 1.4-2.0). We identified a potential association between diabetes mellitus and adenocarcinoma of the esophagus or gastric cardia. This association appears to be independent of obesity. Additionally, nicotine dependence was identified as a risk factor for EAC.
... 47,49 Most studies revealed no altered EAC risk in relation to childbearing history in terms of parity, number of pregnancies, or age at first birth. 46,47,49,[52][53][54][55] However, a decreased risk of EAC associated with breastfeeding has been consistently observed. 46,47,49,52,55 A pooled analysis of three population-based case-control studies found that ever breastfeeding was associated with a 40% reduced risk of EAC and the risk decreased with increasing duration of breastfeeding (RR for > 12 months = 0.42, 95% CI: 0.23 -0.77). ...
... 46,47,49,[52][53][54][55] However, a decreased risk of EAC associated with breastfeeding has been consistently observed. 46,47,49,52,55 A pooled analysis of three population-based case-control studies found that ever breastfeeding was associated with a 40% reduced risk of EAC and the risk decreased with increasing duration of breastfeeding (RR for > 12 months = 0.42, 95% CI: 0.23 -0.77). 49 The protective role of breastfeeding may be related to increased sex hormonal levels, not only estrogens, but also progestogens, and possibly also oxytocin, during pregnancy or breastfeeding. ...
Article
increased rapidly during the past 4 decades in many Western populations, including North America and Europe. The established etiological factors for EAC include gastroesophageal reflux and obesity, Helicobacter pylori infection, tobacco smoking, and consumption of fruit and vegetables. There is a marked male predominance of EAC with a male-to-female ratio in incidence of up to 9:1. This review evaluates the available literature on the reasons for the male predominance, particularly an update on epidemiologic evidence from human studies during the past decade. The striking sex difference does not seem to be explained by established risk factors, given that the prevalence of the etiological factors and the strengths of associations between these factors and EAC risk are similar between the sexes. Sex hormonal factors may play a role in the development of EAC; estrogenic exposures may prevent such development, whereas androgens might increase the risk of EAC. However, continuing research efforts are still needed to fully understand the reasons for the male predominance of EAC.
... Meta-analyses have reported associations between BMI, waist circumference, and waist-to-hip ratio and increased EA/GCA risk (Hoyo et al, 2012;Singh et al, 2013). However, few studies to date have examined early adulthood body weight (Chow et al, 1998;Lagergren et al, 1999;Cheng et al, 2000;Wu et al, 2001;Merry et al, 2007) and body weight change (Chow et al, 1998;Merry et al, 2007); all reported increased risks of EA/GCA with early adulthood obesity and weight gain. One study examined the association between trajectories of body shape, but not BMI, and EA risk. ...
... Our findings extend previous analyses, which have indicated that early adult weight or adult weight change are important in conferring increased risks for EA and GCA (Chow et al, 1998;Lagergren et al, 1999;Cheng et al, 2000;Wu et al, 2001;Merry et al, 2007;Cook et al, 2015) by using correct weight change model specification (Oldham, 1962;Tu and Gilthorpe, 2007) and trajectory modelling (Jones and Nagin, 2007). These approaches have enabled us to identify critical periods for obesity and weight gain, specifically early adult obesity and adult weight gain. ...
Article
Full-text available
Background: Elevated body mass index (BMI, kg m(-2)) has been consistently associated with oesophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) incidence. However, effects of adiposity over the life course in relation to EA/GCA have not been thoroughly explored. Methods: We pooled two prospective cohort studies: NIH-AARP Diet and Health Study and Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, with data on 409 796 individuals (633 EA, 415 GCA). At baseline, participants reported their height and weight at ages 20 and 50 years, and current. Body mass index trajectories were determined using latent class analysis. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Results: Compared with individuals with a BMI<25 kg m(-2) at all time points, exceeding a BMI of 25 kg m(-2) at age 20 was associated with increased risks of EA (HR=1.76, 95% CI: 1.35-2.29) and GCA (HR=1.62, 95% CI: 1.16-2.25). Similarly, a BMI trajectory of overweight (⩾25-<30 kg m(-2)) at age 20 progressing to obesity (⩾30 kg m(-2)) by age 50 was associated with increased risks of EA (HR=2.90, 95% CI: 1.67-5.04) and GCA (HR=4.07, 95% CI: 2.32-7.15), compared with individuals with a normal weight (⩾18.5-<25 kg m(-2)) trajectory. Weight gain of ⩾20 kg between age 20 and baseline was also associated with a two times increased risk of EA (HR=1.97, 95% CI: 1.43-2.73) and more modestly with GCA (HR=1.40, 95% CI: 0.96-2.05). Conclusions: Being overweight in early adulthood and weight gain later in life were each associated with increased risks of EA and GCA. This underscores the potential of weight control programs for reducing EA and GCA risk.British Journal of Cancer (2017) 0, advance online publication: 14 February 2017. doi:10.1038/bjc.2017.29 www.bjcancer.com.
... Furthermore, individuals with a greater propensity to obesity have higher risks of intestinal metaplasia, thereby showing that obesity is independently associated with Barrett oesophagus and its subsequent progression to OAC [14]. Epidemiological studies have also shown a link between leptin and reduced adiponectin, both characteristic of obesity and Barrett oesophagus [15][16][17][18]. However, how obesity and associated changes in adipokines, cytokines, insulin and IGF1-axis, immune mechanisms and their downstream signalling pathways influences Barrett oesophagus and Barrett tumorigenesis at the cellular level is currently unknown. ...
Article
Full-text available
In Barrett associated tumorigenesis, oxidative phosphorylation and glycolysis are reprogrammed early in the disease and act mutually to promote disease progression. However, the link between energy metabolism and its connection with other central cellular processes within the Barrett microenvironment is unknown. The aim of this study was to examine the relationship between metabolism (ATP5B/GAPDH), hypoxia (HIF1α), inflammation (IL1β/SERPINA3), p53 and obesity status using in-vivo and ex-vivo models of Barrett esophagus. At the protein level, ATP5B (r=0.71, P<0.0001) and p53 (r=0.455, P=0.015) were found to be strongly associated with hypoxia. In addition, levels of ATP5B (r=0.53, P=0.0031) and GAPDH (r=-0.39, P=0.357) were positively associated with p53 expression. Moreover, we demonstrate that ATP5B (r=0.8, P<0.0001) and GAPDH (r=0.43, P=0.022) were positively associated with IL1β expression. Interestingly, obesity was negatively associated with oxidative phosphorylation (r=-0.6016, P=0.0177) but positively associated with glycolysis (r=0.743, P0.0015). Comparable correlations were exhibited in the ex-vivo explant tissue between metabolism, p53, hypoxia, inflammation and angiogenesis (P<0.05). Identifying and exploring these underlying molecular mechanisms linking metabolism to these key cellular processes helps in understanding how these different cellular processes interact and could provide some insight into the development of targeted therapies influencing these processes.
... Pre-existing diabetes may increase the risk of mortality by as much as 40% in people with cancer [43]. While gastroesophageal reflux and high body mass index are known as well established risk factors for esophageal cancers [44][45][46], it has also reported that diabetes was associated with substantial and a significant increased risk of esophageal adenocarcinoma [47][48][49][50][51]. ...
Article
Interest in targeting cancer metabolism has been renewed in recent years with the discovery that many cancer related pathways have a profound effect on metabolism and that many tumors become dependent on specific metabolic processes. Accelerated glucose uptake during anaerobic glycolysis and loss of regulation between glycolytic metabolism and respiration, are the major metabolic changes found in malignant cells. The non-metabolizable glucose analog, 2-deoxy-D-glucose inhibits glucose synthesis and adenosine triphosphate production. The adenosine monophosphate-activated protein kinase (AMPK) is a key sensor of cellular energy and AMPK is a potential target for cancer prevention and/or treatment. Metformin is an activator of AMPK which inhibits protein synthesis and gluconeogenesis during cellular stress. This article reviews the status of clinical and laboratory researches exploring targeted therapies via metabolic pathways for treatment of esophageal cancer. Copyright © 2015. Published by Elsevier Inc.
... We retrieved 210 unique articles from the databases of PubMed, Embase, and Web of Science, 61 of which were identified as potentially relevant. After reviewing the full text, we determined that 23 reports met our inclusion criteria (14,19,20,(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48). The literature search and study screening process are shown in Figure 1. ...
Article
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Objective Many laboratory studies have shown that tea consumption protected against the development of esophageal cancer (EC). However, in epidemiological studies, inconsistent or even contradictory results were frequently observed, especially when drinking tea at higher temperatures. Methods We conducted a meta-analysis based on published observational studies to explore whether hot tea consumption was a risk factor of EC. Relevant studies were searched in PubMed, Embase, and Web of science up to October 13, 2021, and we also manually retrieved the literature in the included studies and recent reviews. Results A total of 23 eligible reports were identified, including 5,050 cases and 10,609 controls, and a meta-analysis with Comprehensive Meta-Analysis (CMA) software (version 2.0) was conducted. A statistically significant increased EC risk was observed when drinking tea at higher temperature (odds ratios (ORs) = 1.79, 95% CI: 1.48–2.15, p = 0.00). Except for esophageal adenocarcinoma (EAC), this increased risk was also found in the majority of subgroups, which are the European and Australian populations. Conclusions This meta-analysis showed that people who drank hot tea had a significantly increased risk of Esophageal squamous cell carcinoma (ESCC), but no significant association for EAC.
... The number of EC cases diagnosed in the studies ranged from 47 to 1,310, with a total of 13,811 reported EC cases. Seventeen studies were conducted in China [13,19,20,[25][26][27][28][29][30][31][32][33][34][35][36][37][38], six in Uruguay [11,16,[39][40][41][42], three in Argentina [11,16,43], three in Brazil [11,16,44], three in Paraguay [11,16,45], three in India [46][47][48], three in Iran [15,49,50], two in British [8,51], one in Australia [12], one in Sweden [7], one in Greece [6], one in Kenya [52], and one in Japan [53]. Thirty studies reported results for men and women together, four reported the results for men and women separately, and three reported results for men only and two for women only. ...
Article
Full-text available
Background Previous studies have mostly focused on the effects of specific constituents of beverages and foods on the risk of esophageal cancer (EC). An increasing number of studies are now emerging examining the health consequences of the high temperature of beverages and foods. We conducted a meta-analysis to summarize the evidence and clarify the association between hot beverages and foods consumption and EC risk. Methods We searched the PubMed, Embase, and Web of Science databases for relevant studies, published before May 1, 2014, with the aim to estimate the association between hot beverage and food consumption and EC risk. A random-effect model was used to pool the results from the included studies. Publication bias was assessed by using the Begg test, the Egger test, and funnel plot. Results Thirty-nine studies satisfied the inclusion criteria, giving a total of 42,475 non-overlapping participants and 13,811 EC cases. Hot beverage and food consumption was significantly associated with EC risk, with an odds ratio (OR) of 1.82 (95% confidence interval [CI], 1.53–2.17). The risk was higher for esophageal squamous cell carcinoma, with a pooled OR of 1.60 (95% CI, 1.29–2.00), and was insignificant for esophageal adenocarcinoma (OR: 0.79; 95% CI: 0.53–1.16). Subgroup analyses suggests that the association between hot beverage and food consumption and EC risk were significant in Asian population (OR: 2.06; 95% CI: 1.62-2.61) and South American population (OR: 1.52; 95% CI: 1.25-1.85), but not significant in European population (OR: 0.95; 95% CI: 0.68-1.34). Conclusions Hot beverage and food consumption is associated with a significantly increased risk of EC, especially in Asian and South American populations, indicating the importance in changing people’s dietary habits to prevent EC.
... Radiofrequency ablation (RFA) is an effective and safe therapy for eradication of nondysplastic and dysplastic BE (7,8). Past studies demonstrate a strong association of BE with male sex and Caucasian race (9)(10)(11)(12). ...
Article
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Little is known about differences in Barrett's esophagus (BE) characteristics by sex and race and/or ethnicity or these differences in response to radiofrequency ablation (RFA). We compared disease-specific characteristics, treatment efficacy, and safety outcomes by sex and race and/or ethnicity in patients treated with RFA for BE. The U.S. RFA patient registry is a multicenter collaboration reporting processes and outcomes of care for patients treated with RFA for BE. Patients enrolled with BE. RFA. We assessed safety (stricture, bleeding, perforation, hospitalization), efficacy (complete eradication of intestinal metaplasia [CEIM]), complete eradication of dysplasia, and number of treatments to CEIM by sex and race and/or ethnicity. Among 5521 patients (4052 men; 5126 white, 137 Hispanic, 82 African American, 40 Asian, 136 heritage not identified), women were younger (60.0 vs 62.1 years) and had shorter BE segments (3.2 vs 4.4 cm) and less dysplasia (37% vs 57%) than did men. Women were almost twice as likely to stricture (odds ratio 1.7; 95% confidence interval, 1.2-2.3). Although white patients were predominantly male, about half of African Americans and Asians with BE were female. African Americans and Asians had less dysplasia than white patients. Asians and African Americans had more strictures than did white patients. There were no sex or race differences in efficacy. Observational study with non-mandated paradigms, no central laboratory for reinterpretation of pathology. In the U.S. RFA patient registry, women had shorter BE segments and less-aggressive histology. The usual tendency toward BE in men was absent in African Americans and Asians. Posttreatment stricture was more common among women and Asians. RFA efficacy did not differ by sex or race. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.
... To address this limitation, several meta-analyses have pooled data from recent studies to study some of the possible risk factors at a more granular level. In particular, the Barrett's Oesophagus and Oesophageal Adenocarcinoma Consortium (BOACON), supported by the National Cancer Institute, has pooled data from 13 population-based case-control and two prospective cohort studies to assess risk factors for oesophageal adenocarcinoma and Barrett's oesophagus [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. (Table 1) We herein describe studies of several risk factors and present data syntheses of, typically metaanalyses, provided by different investigators, including those from BOACON. ...
Article
While the incidence rates of many cancers have decreased in past decades, the incidence of oesophageal adenocarcinoma continues to increase. The only known precursor for oesophageal adenocarcinoma is Barrett's oesophagus. Studies conducted have identified white race, male sex, GORD, cigarette smoking, obesity, and the absence of Helicobacter pylori status as risk factors for oesophageal adenocarcinoma. Other potential associations include dietary factors and the absence of non-steroidal anti-inflammatory drug use. Many individual studies have been limited by sample size and several meta-analyses have pooled data from studies to address this limitation. In this review we present a synthesis of these studies and summarize current knowledge of risk factors for both oesophageal adenocarcinoma and Barrett's oesophagus. Copyright © 2014 Elsevier Ltd. All rights reserved.
... Little other data are available for obesity at younger ages. Four case-control studies (Chow et al, 1998;Lagergren et al, 1999b;Cheng et al, 2000;Wu et al, 2001) and one prospective cohort (Merry et al, 2007) evaluated recalled weight, asking their middle-aged participants to recall their height and weight at different ages, including early adulthood. These studies suggest that having an overweight or obese BMI at age 18-and at later time points throughout adulthood-is associated with increased risk of oesophageal adenocarcinoma. ...
Article
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Background: Middle-aged obese adults are at substantially elevated risk of oesophageal adenocarcinoma. It is unclear whether this risk originates earlier in life. Methods: We assessed associations between childhood body mass index (BMI) and height-measured annually between ages 7 and 13-with adult oesophageal adenocarcinoma in a cohort from the Copenhagen School Health Records Register. Analyses included 255 053 children born during 1930-1971. Danish Cancer Registry linkage provided outcomes. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression. Results: During 5.4 million person-years of follow-up, 254 (216 males) incident oesophageal adenocarcinomas occurred. At each examined age, cancer risk increased linearly per unit BMI z-score, although associations were only statistically significant for ages 9-13. The HR for the age of 13 years was 1.31 (95% CI: 1.13, 1.51) per unit BMI z-score. Associations were similar in men and women and across birth cohorts. Childhood height was not related to cancer risk in men but was in women, although these analyses included just 38 female cases. HRs per unit height z-score at the age of 13 years were 1.04 (0.90, 1.19) in males and 1.77 (1.27, 2.47) in females, with similar results observed at the other examined ages. Conclusion: Individuals with higher childhood BMI were at elevated risk of oesophageal adenocarcinoma, even though these cancers occurred many decades later in life. Although the mechanisms require further investigation, our findings provide additional evidence for the long-term health risks of childhood obesity.
... 18,26 A hypothesis that sex hormones are an explanatory factor for this gender difference has been tested, but the results have been conflicting. 44,45 Barrett's esophagus, a columnar metaplasia replacing the normal squamous cell epithelium in the distal esophagus, associated with gastroesophageal reflux, 46 is the strongest known risk factor for development of adenocarcinoma of the esophagus. 47 The occurrence of Barrett's esophagus has been found to be associated with an at least 60-90-fold increase in the risk of esophageal adenocarcinoma. ...
... It is well established that red meat or fat intake increases the risk of adenocarcinoma of the esophagus or gastroesophageal junction. 31,33,35,227,228 Moreover, most studies in Western populations also found an inverse association between intake of fresh vegetables and fruits, or nutrient intake derived from these sources, and the risk of adenocarcinoma of the esophagus, or the gastroesophageal junction, 31,33,35,[227][228][229][230] as well as the risk of esophageal squamous cell carcinoma. 31,35,228 Alcohol intake has been consistently demonstrated as an important and independent risk factor for esophageal squamous cell carcinoma in Western populations, 2 which is also supported by our finding that the "Alcohol drinker" pattern is positively and dose-dependently associated with risk of esophageal squamous cell carcinoma. ...
... ALDH2 rs671 polymorphism and esophageal cancer replacement therapy and long-term breastfeeding reduces the risk of EC. 57,58 We verified the correlation of the ALDH2 rs671 polymorphism and the risk of EC using both hospital-based controls and population-based controls because some biases may exist in hospital-based studies. For example, the hospital-based controls may represent samples of an ill-defined reference population instead of the general population, particularly when the genotypes investigated were associated with the disease under hospital-based controls. ...
Article
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Aldehyde dehydrogenase 2 (ALDH2), a critical enzyme for the detoxification of alcohol, is associated with many types of cancers. To verify the relationship of ALDH2 rs671 G>A polymorphism and esophageal cancer (EC), we performed a meta-analysis of a total of 31 published data including 8,510 patients and 16,197 controls. The pooled odds ratio (OR) and the 95% confidence interval (CI) were calculated using a fixed or random-effects model. Heterogeneity (PH ), publication bias, and sensitivity analysis were also determined. Although a protective effort was found in the rs671 homozygote comparison (AA/GG: OR=0.69; 95% CI=0.48-0.98), the heterozygote comparison was apparently associated with the risk of EC, particularly in the Chinese population ( OR=1.39; 95% CI=1.03-1.87). Alcohol consumption remarkably increased this risk, especially in the AG genotype. Drinking men with the AG genotype appeared to show a higher risk ( OR=4.39; 95% CI=1.24-6.55) than drinking women. The present meta-analysis provided advanced information regarding the association of the ALDH2 A>G polymorphism and EC. Taken together, insights from this study suggested an enhanced effect on the development of EC through a genetic-environmental interaction.
... Some epidemiological studies suggest that the frequency, duration and intensity of reflux symptoms are risk factors for the development of EA. 3 Even though some other studies indicate that EA may be related to obesity, smoking and to a diet low in fresh fruit, these assumptions seem to be controversial. [4][5][6][7] Moreover, the effect of Helicobacter pylori infection, especially of cagA (+) strains, remains in many ways unidentified, although, in the beginning, it had been suggested that it could have a protective role against the EA 8,9 . Therefore, based on the existing data, GERD and especially this one which is complicated with BE, is considered the main risk factor for the development of EA. ...
Article
Esophageal adenocarcinoma presents a more rapidly rising incidence than all other cancers and arises in most patients from its premalignant precursor, Barrett’s esophagus. Barret’s esophagus is associated with chronic GERD and represents the severest form of this disease. PPIs can markedly decrease acid reflux, but only antireflux surgery can successfully restore the function of the incompetent antireflux barrier. Antireflux surgery may be superior to controlling acid reflux alone, because it also eliminates the possible dangerous contributions of bile salts and pancreatic enzymes. However, current data suggest that both medical and surgical therapies are very effective in symptom relief and healing of esophagitis over the long term, but neither treatment predictably causes Barrett’s metaplasia to regress, nor protects the patient from subsequently developing adenocarcinoma of the esophagus. Even if antireflux surgery could prevent esophageal cancer, its use only for this purpose could not be justified because the surgical mortality rate, at least 0,2%, far exceeds the annual incidence of cancer, estimated at 0,07%. Therefore, it seems prudent for gastroenterologists and surgeons to be honest with their patients about the outcomes of current established treatments of GERD. Given this information, and after a thoughtful discussion of both therapies, we believe patients can choose the regimen that best suits their individual needs.
... During the natural history of esophageal adenocarcinoma from reflux, to Barrett's esophagus to cancer, the male-to-female sex ratio progressively increases, culminating in more than seven males for every female with cancer (Cook et al., 2005(Cook et al., , 2009). This stark sex disparity has been repeatedly observed, yet underlying causes have not been identified (Cheng et al., 2000;Lindblad et al., 2005;Lofdahl et al., 2008;Cook et al., 2010Cook et al., , 2012Cook et al., , 2014aRutegard et al., 2010;Bodelon et al., 2011;Freedman et al., 2011;Hoyo et al., 2012;Kubo et al., 2013). Sex steroid hormones have been hypothesized to be a possible cause (Lagergren & Nyren, 1998) and the fact that sex steroid hormones are involved in inflammatory processes (Maggio et al., 2005;Schmidt et al., 2006;Kupelian et al., 2010;Liao et al., 2012) and that sex steroid hormone receptor proteins are expressed in esophageal tissues (Rashid et al., 2010;Yang et al., 2012) support such a proposition. ...
Article
Previously, we observed strong positive associations between circulating concentrations of free testosterone and free dihydrotestosterone (DHT) in relation to Barrett's esophagus in a US male military population. To replicate these findings, we conducted a second study of sex steroid hormones and Barrett's esophagus in the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study based in Northern Ireland and Ireland. We used mass spectrometry to quantitate EDTA plasma concentrations of nine sex steroid hormones and ELISA to quantitate sex hormone-binding globulin in 177 male Barrett's esophagus cases and 185 male general population controls within the FINBAR Study. Free testosterone, free DHT, and free estradiol were estimated using standard formulas. Multivariable logistic regression estimated odds ratios (OR) and 95% confidence intervals (95%CI) of associations between exposures and Barrett's esophagus. While plasma hormone and sex hormone-binding globulin concentrations were not associated with all cases of Barrett's esophagus, we did observe positive associations with estrogens in younger men (e.g. estrone + estradiol ORcontinuous per ½IQR = 2.92, 95%CI:1.08, 7.89), and free androgens in men with higher waist-to-hip ratios (e.g. free testosterone ORcontinuous per ½IQR = 2.71, 95%CI:1.06, 6.92). Stratification by body mass index, antireflux medications, and geographic location did not materially affect the results. This study found evidence for associations between circulating sex steroid hormones and Barrett's esophagus in younger men and men with higher waist-to-hip ratios. Further studies are necessary to elucidate whether sex steroid hormones are consistently associated with esophageal adenocarcinogenesis.
... The search identified 15,009 studies. Among these, 52 studies fulfilled the inclusion criteria and were enrolled to this meta-analysis (Figure 1) (45,49). Two studies from Uruguay had partly overlapping study periods (52,53). ...
Article
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Background Tobacco smoking strongly increases risk of esophageal squamous cell carcinoma and moderately increases risk of esophageal adenocarcinoma. How smoking cessation influences esophageal cancer risk across histological subtypes, time latencies, and geographic regions is not clear. Methods Studies were systematically searched on Medline, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov. Pooled estimates of risk ratios (RRs) were derived using a random effects model. Cochran’s Q test and I² statistic were used to detect heterogeneity. Results Among 15 009 studies, 52 fulfilled the inclusion criteria. Using nonsmokers as a reference, risk of esophageal squamous cell carcinoma was lower among former smokers (RR = 2.05, 95% confidence interval [CI] = 1.71 to 2.45) than among current smokers (RR = 4.18, 95% CI = 3.42 to 5.12). Compared with current smokers, a strong risk reduction was evident after five or more years (RR = 0.59, 95% CI = 0.47 to 0.75), and became stronger after 10 or more years (RR = 0.42, 95% CI = 0.34 to 0.51) and 20 or more years (RR = 0.34, 95% CI = 0.25 to 0.47) following smoking cessation. The risk reduction was strong in Western populations, while weak in Asian populations. Using nonsmokers as reference, the risk of esophageal adenocarcinoma was only slightly lower among former smokers (RR = 1.66, 95% CI = 1.48 to 1.85) than among current smokers (RR = 2.34, 95% CI = 2.04 to 2.69). The risk of esophageal adenocarcinoma did not show any clear reduction over time after smoking cessation, with a risk ratio of 0.72 (95% CI = 0.52 to 1.01) 20 or more years after smoking cessation, compared with current smokers. Conclusions Smoking cessation time-dependently decreases risk of esophageal squamous cell carcinoma, particularly in Western populations, while it has limited influence on the risk of esophageal adenocarcinoma.
... A possible protective role of fruit in reducing EAC risk was confirmed in several studies. Cheng et al. [38] showed the strong protective effect of high fruit consumption in women with a clear linear trend (p = 0.003) from the lowest to the highest level of intake. Also, Anderson et al. [32] showed a protective role of fruit [OR=0.50 ...
Preprint
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One of the most notable changes in the Esophageal Cancer (EC) epidemiology is the rising incidence and prevalence of esophageal adenocarcinoma (EAC) in developed countries, likely due to lifestyle and/or environmental factors that may play an important role in EAC onset. The aim of this systematic review was to collect and summarize all the available evidence regarding lifestyle, diet and EAC risk. We searched the PubMed and Scopus databases in January 2021 for studies providing information about lifestyle, diet, WCRF/AICR recommendations and EAC risk. A total of 106 publications met the inclusion criteria. Body mass index (BMI) and waist circumference (WC) are associated with increased EAC risk. Physical activity does not appear to have a significant direct role in EAC risk. A diet rich in fruit, vegetables, and whole grains appeared to be more protective than a diet rich in animal fat, red meat, and processed meat. Alcohol does not seem to be related to EAC whereas smokers, particularly heavy smokers, have an increased risk of EAC. Primary prevention remains the best option to avert EAC. BMI and WC, along with low consumption of red and processed meat, high consumption of plant food, and the avoidance of smoking are pivotal for EAC prevention.
... Interestingly, a dose-dependent risk reduction in EC by breastfeeding was suggested [19]. In a recent study, based on pooled data from several large case-control studies, endogenous reproductive factors and exogenous factors were evaluated in women. ...
Chapter
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Esophageal cancer (EC) affects men far more commonly than women. Numerous epidemiological studies have suggested that the hormonal milieu may play a role in this gender bias. However, there is little known about circulating sex hormone levels in relation to the risk of EC development. In this chapter, the correlation between circulating sex hormone levels and mRNA expression of estrogen receptors (ER) in normal esophageal mucosal samples and EC biopsies from patients with potentially resectable EC is studied. Moreover, the association of serum sex hormones levels with and clinico-pathological features of EC is analysed.
... In the distal esophageal adenocarcinoma, several risk factors have been identified including male sex, white ethnicity, high body mass index (BMI), obesity, gastroesophageal reflux disease (GERD), Barrett esophagus, lack of infection with H pylori, and low fruit and vegetable intake. [6][7][8][9][10][11] However, somewhat different risk factors for gastric cancer have been identified. H pylori infection is the main etiology, and the other risk factors include alcohol drinking, smoking, and dietary factors-high salt, high sodium intake, and low fruit intake. ...
Article
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There are still many controversies about the characteristics and prognosis of gastric cardia cancer. We aimed to evaluate the clinical characteristics and outcome between cardia and noncardia cancer. Also, we evaluated the clinical outcome according to etiologic factors.We performed a retrospective cohort study of 92 patients with gastric cardia cancer from January 2003 to December 2013. The patients with noncardia cancer were selected as age- and sex-matched control.The frequencies of gastroesophageal reflux disease (GERD) and negative Helicobacter pylori infection without atrophy were significantly higher in gastric cardia cancers, but there was no difference in the frequency of obesity. The frequency of early gastric cancers was 40.0%, which was significantly lower than that of noncardia cancer. The rate of recurrence, disease-free survival, and overall survival duration were significantly lower in gastric cardia cancers (P < .01), even though there was no significant difference in the rate of curative resection (R0). In terms of the etiologic factors, there were no differences of disease prognosis, regardless of the presence of GERD, obesity, and H pylori infection with associated gastritis.Gastric cardia cancer showed distinct clinical characteristics and a negative prognostic impact compared with gastric noncardia cancer.
... In prior studies, excess early-adulthood weight status or adult weight gain has each, independently, been associated with increased risk of EA and GCA (9,14,(31)(32)(33)(34)(35). Our findings extend these analyses by examining weight changes between childhood (ages 7 and 13) and early adulthood. ...
Article
Objective: Esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) are among the most rapidly increasing cancers in Western countries. Elevated BMI in adulthood is a known risk factor, but associations in early life are unclear. Methods: This study assessed weight change between childhood and early adulthood in relation to EA/GCA. Measured weights and heights during childhood (7-13 years) and early adulthood (17-26 years) were available for 64,695 young men from the Copenhagen School Health Records Register and the Danish Conscription Database. Individuals were categorized as having normal weight or overweight. Linkage with the Danish Cancer Registry identified 275 EA/GCA cases. Hazard ratios (HR) and 95% CI were estimated using Cox proportional hazards regression. Results: The risk of EA/GCA was 2.5 times higher in men who were first classified as having overweight at age 7 (HR = 2.49; 95% CI: 1.50-4.14) compared with men who were never classified as having overweight. Men who had persistent overweight at ages 7 and 13 and in early adulthood had an EA/GCA risk that was 3.2 times higher (HR = 3.18; 95% CI: 1.57-6.44). However, there was little evidence of increased EA/GCA risk for men with overweight during childhood and subsequent remittance by early adulthood. Conclusions: Persistent overweight in early life is associated with increased EA/GCA risk, which declines if body weight is reduced.
... Apart from these malignancies, epidemiological evidence of the associations between body fatness at a young age and other malignancies has been accumulating within the past few decades . A number of studies have investigated the associations between body fatness at a young age and cancers of the pancreas (34)(35)(36)(37)(38)(39)(40)(41)(42)(43), renal cell (44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55) and thyroid (56)(57)(58)(59)(60)(61)(62), as well as DLBCL (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17); fewer studies have reported associations between body fatness at a young age and hepatocellular carcinoma (26)(27)(28)(29), multiple myeloma (12,14,(30)(31)(32)(33) and adenocarcinomas of the oesophagus (18)(19)(20)(22)(23)(24)(25) and gastric cardia cancer (18,(20)(21)(22)25). The associations between body fatness at a young age and these malignancies remain inconclusive, as most studies on body fatness at a young age showed a tendency towards increased risks of these malignancies, but only a few reached statistical significance, probably because the small number of cases with each cancer type limits the statistical power to detect weak associations. ...
Article
The associations between body fatness at a young age (childhood, adolescence and young adulthood; age ≤ 30 years) and diffuse large B‐cell lymphoma (DLBCL), oesophageal adenocarcinoma, gastric cardia cancer, hepatocellular carcinoma, multiple myeloma, pancreatic cancer, renal cell cancer and thyroid cancer remain inconclusive. We performed a comprehensive systematic literature review and meta‐analysis of observational studies to clarify the associations between body fatness at a young age and the risks of these cancers. PubMed and Web of Science databases were searched for relevant observational studies. Fifty‐six articles yielded data on 27,559 cancer cases, including 3,170 DLBCL, 1,491 oesophageal adenocarcinoma, 1,103 gastric cardia cancer, 1,067 hepatocellular carcinoma, 3,090 multiple myeloma, 7,220 pancreatic cancer, 6,212 renal cell cancer and 4,206 thyroid cancer cases. Each 5 kg m−2 increase in body mass index at a young age was positively associated with DLBCL (relative risk [RR] 1.21, 95% confidence interval [CI] 1.09, 1.35), oesophageal adenocarcinoma (RR 1.88, 95% CI 1.37, 2.57), gastric cardia cancer (RR 1.59, 95% CI 1.15, 2.21), hepatocellular carcinoma (RR 1.31, 95% CI 1.13, 1.51), multiple myeloma (RR 1.23, 95% CI 1.15, 1.30), pancreatic cancer (RR 1.17, 95% CI 1.11, 1.24), renal cell cancer (RR 1.22, 95% CI 1.16, 1.28) and thyroid cancer (RR 1.12, 95% CI 1.07, 1.17). In summary, higher body fatness at a young age increases the risks of developing various types of cancer later in life. Prevention of overweight and obesity in children, adolescents and young adults should therefore be emphasized to reverse the obesity epidemic and thereby avoid further increases in the burden of cancer attributed to excess body fatness.
Chapter
For all patients with esophageal cancer, the five‐year survival rate is about 20%. The two most common histopathologic subtypes of esophageal cancer are squamous cell carcinoma and adenocarcinoma. This chapter focuses on the epidemiology, pathogenesis, clinical presentation and diagnosis, staging, and endoscopic therapies for malignant esophageal cancers. The epidemiology of esophageal cancer has changed significantly over the last 40 years, with adenocarcinoma becoming much more common than squamous cell carcinoma in the Western world. Benign esophageal tumors are rare. They are usually asymptomatic and discovered incidentally on endoscopy for evaluation for an unrelated problem. The chapter provides information on the clinical presentation, diagnosis, histopathology, and management of some of the more common benign esophageal neoplasms. Endoscopic ultrasound can assist in establishing the nature of the lesions by determining the originating gastrointestinal tract layer.
Chapter
Esophageal adenocarcinoma and squamous cell carcinoma are associated with defined risk factors and tend to develop over time with progression from normal to pre-neoplasia to neoplasia and frank malignancy. In this chapter, we review the pathology of esophageal adenocarcinoma and its precursor lesions, Barrett’s esophagus, and Barrett’s-associated dysplasia. We also review squamous cell carcinoma and squamous dysplasia. We discuss how biopsy, endoscopic mucosal resection, and esophagectomy specimens are assessed, including the challenges in diagnosis and pathologic staging of these specimens. Finally, we touch upon theragnostic tests, including HER2, microsatellite instability, and PD-L1, that are performed in the pathology laboratory and provide information that identified patients who will benefit most from these targeted therapies.
Article
Background: Diabetes is positively associated with various cancers, but its relationship with tumors of the esophagus/esophagogastric junction remains unclear. Methods: Data were harmonized across 13 studies in the International Barrett's and Esophageal Adenocarcinoma Consortium, comprising 2309 esophageal adenocarcinoma (EA) cases, 1938 esophagogastric junction adenocarcinoma (EGJA) cases, 1728 Barrett's esophagus (BE) cases, and 16,354 controls. Logistic regression was used to estimate study-specific odds ratios (ORs) and 95% CIs for self-reported diabetes in association with EA, EGJA, and BE. Adjusted ORs were then combined using random-effects meta-analysis. Results: Diabetes was associated with a 34% increased risk of EA (OR, 1.34; 95% CI, 1.00-1.80; I2 = 48.8% [where 0% indicates no heterogeneity, and larger values indicate increasing heterogeneity between studies]), 27% for EGJA (OR, 1.27; 95% CI, 1.05-1.55; I2 = 0.0%), and 30% for EA/EGJA combined (OR, 1.30; 95% CI, 1.06-1.58; I2 = 34.9%). Regurgitation symptoms modified the diabetes-EA/EGJA association (P for interaction = .04) with a 63% increased risk among participants with regurgitation (OR, 1.63; 95% CI, 1.19-2.22), but not among those without regurgitation (OR, 1.03; 95% CI, 0.74-1.43). No consistent association was found between diabetes and BE. Conclusions: Diabetes was associated with increased EA and EGJA risk, which was confined to individuals with regurgitation symptoms. Lack of an association between diabetes and BE suggests that diabetes may influence progression of BE to cancer.
Chapter
Cohesive scientific evidence from molecular, animal, and human investigations supports the hypothesis that aberrant induction of COX-2 and up-regulation of the prostaglandin cascade play a significant role in carcinogenesis, and reciprocally, blockade of the process has strong potential for cancer prevention and therapy. Supporting evidence includes the following: [1] expression of constitutive COX-2-catalyzed prostaglandin biosynthesis is induced by most cancer-causing agents including tobacco smoke and its components (polycylic aromatic amines, heterocyclic amines, nitrosamines), essential polyunsaturated fatty acids (unconjugated linoleic acid), mitogens, growth factors, proinflammatory cytokines, microbial agents, tumor promoters, and other epigenetic factors, [2] COX-2 expression is a characteristic feature of all premalignant neoplasms, [3] COX-2 expression is a characteristic feature of all malignant neoplasms, and expression intensifies with stage at detection and cancer progression and metastasis, [4] all essential features of carcinogenesis (mutagenesis, mitogenesis, angiogenesis, reduced apoptosis, metastasis, and immunosuppression) are linked to COX-2-driven prostaglandin (PGE-2) biosynthesis, [5] animal studies show that COX-2 up-regulation (in the absence of genetic mutations) is sufficient to stimulate the transformation of normal cells to invasive cancer and metastatic disease, [6] non-selective COX-2 inhibitors, such as aspirin and ibuprofen, reduce the risk of human cancer and precancerous lesions, and [7] selective COX-2 inhibitors, such as celecoxib, reduce the risk of human cancer and precancerous lesions at all anatomic sites thus far investigated. Results confirming that COX-2 blockade is effective for both cancer prevention and therapy have been tempered by observations that some COX2 inhibitors pose a risk to the cardiovascular system, and more studies are needed in order to determine if certain of these drugs can be taken at dosages that prevent cancer without increasing cardiovascular risk. It is emphasized that the "inflammogenesis model of cancer" is not mutually exclusive and may in fact be synergistic with the accumulation of somatic mutations in tumor suppressor genes and oncogenes or epigenetic factors in the development of cancer.
Article
Like most structures of the alimentary canal, the esophagus is a tubular muscular structure that contains a mucosa, submucosa, muscularis propria, and surrounding connective tissue (termed adventitia in the esophagus) (Fig. 3.1). Anatomically, the esophagus extends from the cricopharyngeal muscle, which forms the upper esophageal sphincter, to the lower esophageal junction, where the stomach originates. Histologically, the mucosa consists of a stratifi ed non-keratinizing squamous epithelium, lamina propria, and muscularis mucosae. The squamous epithelium sits atop a basement membrane that separates it from the lamina propria. The lamina propria is composed of loose fi broconnective tissue, lymphatic spaces, and capillary vessels. The muscularismucosae is a thin muscular layer that separates the mucosa from the submucosa. The submucosa is composed of dense irregular fi brovascular connective tissue admixed withscattered mucin-producing glands (esophageal submucosal glands) and ducts, which aidinthe passage of food. Deep to the submucosa is the muscularis propria, which is primarily composed of striated muscle in the upper 1/3 of the esophagus, smooth muscle in the lower 1/3 of the esophagus, and a mixture of both in the mid esophagus. Finally, deep to the muscularis propria is the adventitia, a layer of connective tissue andadipose tissue that helps link the esophagus to adjacent structures. The esophagus, unlike most tubular structures of the alimentary canal, lacks a serosa.
Article
Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC). Based on striking aggregation of breast cancer and BE/EAC within families as well as shared risk factors and molecular mechanisms of carcinogenesis, we hypothesized that BE may be associated with breast cancer. Pedigree analysis of families identified prospectively at multiple academic centers as part of the Familial Barrett's Esophagus Consortium (FBEC) was reviewed and families with aggregation of BE/EAC and breast cancer are reported. Additionally, using a matched case-control study design, we compared newly diagnosed BE cases in Caucasian females with breast cancer (cases) to Caucasian females without breast cancer (controls) who had undergone upper endoscopy (EGD). Two familial pedigrees, meeting a stringent inclusion criterion, manifested familial aggregation of BE/EAC and breast cancer in an autosomal dominant inheritance pattern with incomplete penetrance. From January 2008 to October 2016, 2812 breast cancer patient charts were identified, of which 213 were Caucasian females who underwent EGD. Six of 213 (2.82%) patients with breast cancer had pathology-confirmed BE, compared to 1 of 241 (0.41%) controls (P-value < 0.05). Selected families with BE/EAC show segregation of breast cancer. A breast cancer diagnosis is marginally associated with BE. We postulate a common susceptibility between BE/EAC and breast cancer.
Article
Context: Esophageal cancer is a neoplasm with a poor prognosis. Its two histologic subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have been associated with different risk factors. The possibility of an association between the consumption of hot food and beverages and esophageal cancer, especially ESCC, has long been suspected, presenting a potentially modifiable risk factor. A meta-analysis of existing observational studies was performed to provide a quantitative estimate of the risk of esophageal cancer associated with the consumption of hot food and drink. Evidence acquisition: A search was conducted through MEDLINE, PubMed, EMBASE, and Current Contents Connect to November 11, 2014. Pooled ORs and 95% CIs were calculated using a random effects model for the risk of esophageal cancer associated with the consumption of hot food and drink. Subgroup analyses were conducted for ESCC and EAC, as well as for studies that adjusted for tobacco smoking and alcohol consumption, two well-recognized risk factors for ESCC. Evidence synthesis: Consumption of hot food and drink was associated with an increased risk of any esophageal cancer (OR=1.90, 95% CI=1.46, 2.48). Heterogeneity was observed. There was an increased risk of ESCC (OR=2.29, 95% CI=1.79, 2.93), which remained even after adjusting for significant confounding variables (OR=2.39, 95% CI=1.71, 3.33). The relationship was not significant for EAC. Conclusions: The consumption of hot food and beverages was associated with an increased risk of esophageal cancer, particularly ESCC.
Article
Smoking cigarettes and drinking alcoholic beverages are considered very important risk factors for adverse health effects, such as many types of cancer and cardiovascular disease. In this study, we evaluated the influence of smoking and drinking cessation on risk of esophageal cancer, by means of meta-analysis. We extracted 205 studies by conducting a systematic literature search. Thirty-five studies that estimated risk reduction following smoking cessation and 18 studies conducted following drinking cessation were identified in the literature review. Former smokers had a significantly lower summary risk ratio (RR) than current smokers [RR 0.74, 95% confidence interval (CI) 0.68–0.80]. In subgroup analysis of Japanese smokers, squamous cell carcinoma, and adenocarcinoma, RRs for former smokers versus current smokers were 0.65 (95% CI 0.51–0.83), 0.60 (95% CI 0.50–0.72), and 0.93 (95% CI 0.84–1.03), respectively. The summary RR between former alcohol drinkers and current drinkers was not significant (RR 1.09, 95% CI 0.94–1.26). In our analysis of time since drinking cessation, drinkers who had stopped consuming alcohol for 5 years or more had a significantly lower summary RR than current drinkers (RR 0.78, 95% CI 0.66–0.93). Summary RR for drinkers who stopped for 10 years or more versus current drinkers was 0.65 (95% CI 0.57–0.74). Our investigation found that smoking cessation lowers esophageal cancer incidence. We also found that esophageal cancer incidence risk could be decreased in current drinkers by cessation of alcohol consumption for 5 years or more.
Article
Esophageal tumors range from rare benign tumors, such as papillomas and leiomyomas, to malignant tumors with squamous cell and adenocarcinoma being the most commonly encountered lesions. The survival rates of patients with malignant esophageal tumors remain poor. Endoscopy and endoscopic ultrasound are critical in the diagnosis, staging, and potential treatment of early, superficial cancers, and can offer palliation to advanced, unresectable lesions. This chapter reviews the epidemiology, pathogenesis, diagnosis, staging, and treatment of both benign and malignant esophageal tumors.
Chapter
Norman Rupert Barrett, d’origine anglaise, est né en 1903 à Adélaïde (Australie). La famille retourna peu après en Angleterre, où Norman bénéficia de la traditionnelle éducation d’Eton et du Trinity College à Cambridge. Après de brillantes études médicales et des fonctions de résident à l’hôpital Saint Thomas, il fut nommé, en 1928, Master en chirurgie. En 1935, bénéficiant d’une bourse Rockefeller, il passa un an aux états-Unis à la Mayo Clinic. Ce stage révéla sa personnalité alors qu’il était exposé aux avancées rapides de la chirurgie américaine de l’époque, ceci contrastant avec les méthodes relativement sobres qui étaient en vogue de l’autre côté de l’Atlantique. Dès lors, plusieurs liens solides et amicaux se sont créés avec les équipes américaines qu’il put utiliser par la suite.
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Esophageal cancer is the 8th most common cancer worldwide, and its mortality remains unacceptably high, with an overall 5-year survival rate of 20%. Males are more affected than females, and the peak incidence is in the sixth decade of life. Symptoms tend to arise late in the course of the disease, and commonly include dysphagia, odynophagia, and weight loss. Its main histological subtypes are squamous cell carcinoma (SCC) and adenocarcinoma. SCC is the most prevalent histology, but it has been surpassed in developed countries by adenocarcinoma over the last few decades subsequent to the rise in obesity and the decline of smoking and alcohol use. Imaging is essential to the management of esophageal cancer, as it guides clinical staging. Initial staging is multimodal, usually comprising endoscopic and cross-sectional imaging. 2-Deoxy-2-[18F]fluoroglucose (¹⁸F- FDG) PET/CT plays an important role in metastases detection of distant disease, measurement of treatment response, and in the surveillance for recurrences post-esophagectomy. The metabolic information provided by the ¹⁸F- FDG PET adds to the anatomic data CT yields, resulting in a synergistic modality capable of influencing clinical management in esophageal cancer. Moreover, there is mounting evidence supporting the use of ¹⁸F- FDG PET standardized uptake value as an objective way to measure treatment response and even as a prognostic resource. More recent developments in the use of hybrid imaging combining nuclear medicine and radiology techniques culminated in PET/magnetic resonance imaging (MRI), which shows promising results in preliminary studies. Similar efforts have been put into the development of new radiopharmaceuticals that might enhance the diagnostic efficacy of PET imaging. Nuclear medicine is currently essential to provide the oncologist with fundamental information to guide esophageal cancer management and will continue to do so as new technologies are constantly being refined and tested.
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There are considerable variations in the incidence of esophageal adenocarcinoma (EA) related to geographic regions and demographic features. EA is one of the few cancers whose incidence is increasing in the United States. Despite advances in therapy, survival from EA remains low. Multiple risk factors may affect the development of EA or its precursor, Barrett's Esophagus, including gastroesophageal reflux disease, smoking, obesity, use of PPIs, Helicobacter pylori infection, statins, aspirin and non-steroidal anti-inflammatory drugs, bisphosphonates, diet and possible genetic factors. © 2001, 2006, 2015 by John Wiley & Sons, Ltd. All rights reserved.
Chapter
Oesophageal cancer is the third most common gastrointestinal malignancy worldwide. Over the last 40 years, the UK has seen a rise in prevalence and it is now the 13th most common cancer in adults [1]. It has an incidence of 8,300 new cases each year demonstrating a 2:1 preference for males to females. It is reported that 80 % of new cases are diagnosed in patients over 60 years of age [1]. The distribution of tumour subtype varies according to ethnicity with adenocarcinoma favouring Caucasians and squamous cell carcinomas favouring Asian, South American and African populations [2]. Despite advances in multimodality treatment, oesophageal cancer is still devastatingly aggressive with over 65 % of new cases incurable at time of presentation. The disease maintains a 5-year survival of just 15–20 % [3].
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Incidence rates have risen rapidly for esophageal adenocarcinoma and moderately for gastric cardia adenocarcinoma, while rates have remained stable for esophageal squamous cell carcinoma and have declined steadily for noncardia gastric adenocarcinoma. We examined anthropometric risk factors in a population-based case-control study of esophageal and gastric cancers in Connecticut, New Jersey, and western Washington. Healthy control subjects (n = 695) and case patients with esophageal squamous cell carcinoma or noncardia gastric adenocarcinoma (n = 589) were frequency-matched to case patients with adenocarcinomas of esophagus or gastric cardia (n = 554) by 5-year age groups, sex, and race (New Jersey only). Classification of cases by tumor site of origin and histology was determined by review of pathology materials and hospital records. Data were collected using in-person structured interviews. Associations with obesity, measured by body mass index (BMI), were estimated by odds ratios (ORs). All ORs were adjusted for geographic location, age, sex, race, cigarette smoking, and proxy response status. The ORs for esophageal adenocarcinoma rose with increasing adult BMI. The magnitude of association with BMI was greater among the younger age groups and among nonsmokers. The ORs for gastric cardia adenocarcinoma rose moderately with increasing BMI. Adult BMI was not associated with risk of esophageal squamous cell carcinoma or noncardia gastric adenocarcinoma. Increasing prevalence of obesity in the United States population may have contributed to the upward trends in esophageal and gastric cardia adenocarcinomas.
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Adenocarcinomas of the esophagus and gastric cardia were once rare. However, for unknown reasons, their incidence has been increasing rapidly over the past 15 years in the United States and parts of Western Europe. In contrast, the incidence of esophageal squamous cell carcinomas has remained relatively constant. To investigate possible reasons for these diverging incidence rates we analyzed data from two population-based case-control studies of cancers of the esophagus and gastric cardia that were conducted among male and female residents of western Washington between 1983 and 1990. Information on body mass index, cigarette use, alcohol intake, and other possible risk factors was collected via personal interviews with 404 cases or their next of kin (including 298 adenocarcinomas and 106 squamous cell carcinomas) and 724 controls identified by random digit dialing. Use of alcohol and cigarettes were significant risk factors for both histological types. The increase in risk for current smokers of 80 or more pack-years compared to nonsmokers was substantially higher for squamous cell cancer [odds ratio (OR) = 16.9; 95% confidence interval (CI) = 4.1-69.1] than for adenocarcinoma (OR = 3.4; 95% CI = 1.4-8.0), as was the increase for persons who typically drank 21 or more drinks/week compared to those who drank <7/week (OR = 9.5; 95% CI = 4.1-22.3 versus OR = 1.8; 95% CI = 1.1-3.1). For squamous cell carcinoma, body mass index was inversely associated with risk, whereas for adenocarcinoma, the highest risk was observed among persons who were in the highest decile of body mass index (OR = 1.9; 95% CI = 1.1-3.2).(ABSTRACT TRUNCATED AT 250 WORDS)
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Obesity is generally defined as a body mass index (BMI) of 30 kg/m2 and higher. Overweight is defined as a BMI between 25 and 30 kg/m2. The prevalence varies considerably between countries, and between regions within countries. It is estimated that more than half of adults aged 35-65 living in Europe are either overweight or obese. Overweight is more common among men than among women but obesity is more common among women. The prevalence of obesity in Europe is probably in the order of 10-20% in men and 15-25% in adult women. In most European countries who have reliable data on time-trends the prevalence of obesity seems to be increasing. In most European countries, obesity is usually inversely associated with socio-economic status, particularly among women. New classifications of overweight may be based on cut-off points for simple anthropometric measures which reflects both total adiposity as well as abdominal fatness.
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Incidence rates for adenocarcinomas of the esophagus and gastric cardia have risen steeply over the last few decades. To determine risk factors for these tumors, we conducted a multicenter, population-based, case-control study. The study included 554 subjects newly diagnosed with esophageal or gastric cardia adenocarcinomas, 589 subjects newly diagnosed with esophageal squamous cell carcinoma or other gastric adenocarcinomas, and 695 control subjects. Estimates of risk (odds ratios [ORs] and corresponding 95% confidence intervals [CIs]) were calculated for the four tumor types separately and for esophageal and gastric cardia adenocarcinomas combined. Risk of esophageal and gastric cardia adenocarcinomas combined was increased among current cigarette smokers (OR = 2.4; 95% = 1.7-3.4), with little reduction observed until 30 years after smoking cessation; this risk rose with increasing intensity and duration of smoking. Risk of these tumors was not related to beer (OR = 0.8; 95% CI = 0.6-1.1) or liquor (OR = 1.1; 95% CI = 0.8-1.4) consumption, but it was reduced for drinking wine (OR = 0.6; 95% CI = 0.5-0.8). Similar ORs were obtained for the development of noncardia gastric adenocarcinomas in relation to tobacco and alcohol use, but higher ORs were obtained for the development of esophageal squamous cell carcinomas. For all four tumor types, risks were higher among those with low income or education. Smoking is a major risk factor for esophageal and gastric cardia adenocarcinomas, accounting for approximately 40% of cases. Because of the long lag time before risk of these tumors is reduced among ex-smokers, smoking may affect early stage carcinogenesis. The increase in smoking prevalence during the first two thirds of this century may be reflected in the rising incidence of these tumors in the past few decades among older individuals. The recent decrease in smoking may not yet have had an impact.
Article
Analyses of cancer incidence data from nine areas of the United States revealed steadily rising rates from 1976 to 1987 of adenocarcinomas of the esophagus and gastric cardia. The increases among men in this period ranged from 4% to 10% per year, and thus exceeded those of any other type of cancer. In contrast, there were relatively stable trends for squamous cell carcinoma of the esophagus and slight declines for adenocarcinoma of more distal portions of the stomach. Adenocarcinomas of the esophagus and gastric cardia disproportionately affected white men and rarely occurred among women. By the mid-1980s, among white men, adenocarcinomas accounted for about one third of all esophageal cancers, while cardia cancers accounted for about one half of all stomach cancers with specified subsites. The rising incidence rates and similar demographic patterns point to the need for investigation into the causes of these poorly understood cancers.
Article
Data in a regional cancer registry covering a population of 5 million and with an efficiency of registration of over 95% have been used to examine incidence trends in oesophageal and gastric carcinoma. In the West Midlands Region of the UK, during the period 1962 to 1981 the age standardised incidence of gastric carcinoma decreased by 20%. However, an analysis by both histological type and detailed site reveals that while the incidence of distal lesions is diminishing, the incidence of adenocarcinoma of the oesophagus and cardia is increasing. The proximal and distal lesions also exhibit marked differences in social class distribution and sex ratio. The results strongly suggest that the aetiological factors involved for cardia and adjoining sites are different from those for pyloric antrum.
Article
A straightforward and unified approach is presented for the calculation of the population attributable risk per cent (etiologic fraction) in the general multivariate setting, with emphasis on using data from case-control studies. The summary attributable risk for multiple factors can be estimated, with or without adjustment for other (confounding) risk factors. The relation of this approach to procedures in the literature is discussed. Given values of the relative risks for various combinations of factors, all that is required is the distribution of these factors among the cases only. The required information can often be estimated solely from case-control data, and in some situations relative risk estimates from one population can be applied to calculation of attributable risk for another population. The authors emphasize the benefits to be obtained from logistic regression models, so that risks need not be estimated separately in a large number of strata, some of which may contain inadequate numbers of individuals. This approach allows incorporation of important interactions between factors, but does not require that all possible interactions be included. The approach is illustrated with data on four risk factors from a pair-matched case-control study of participants in a multicenter breast cancer screening project.
Article
About one-half of patients with insulin- or non-insulin-dependent diabetes have delayed gastric emptying (diabetic gastroparesis). Some of them complain of epigastric pain, nausea, vomiting or postprandial fullness (diabetic dyspepsia), although only a minority are severely symptomatic. Diabetic gastroparesis is clinically relevant not only by virtue of the symptoms induced but also because it may contribute to inadequate glycaemic control and impaired absorption of orally administered drugs. Recent data suggest that abnormal blood glucose control, not only autonomic neuropathy, contribute to the pathogenesis of disordered gastric motility. In most cases diabetic gastroparesis is diagnosed clinically in the absence of demonstrable lesions of the upper gastrointestinal tract. To evaluate gastric emptying, scintigraphy is the 'gold standard'. Gastrokinetic drugs are of help in the treatment of gastroparesis: erythromycin is the first choice in acute presentations and cisapride for chronic symptoms. New macrolides with prokinetic action and devoid of antibacterial properties are very promising and should add another pharmacologic approach to control dyspepsia and gastroparesis in diabetic patients in the future.
Article
In the United States, the incidence of adenocarcinoma of the esophagus, including the esophagogastric junction, has been increasing rapidly over the past two decades. Except for an association with Barrett's esophagus, little is known about the etiology of these cancers. Our purpose was to investigate dietary and nutritional risk factors for adenocarcinoma of the esophagus. A population-based, case-control interview study of 174 white men with adenocarcinoma of the esophagus and 750 control subjects living in three areas of the United States was conducted during 1986 through 1989. Risk was significantly elevated for subjects in the heaviest quartile compared with the lightest quartile of body mass index (odds ratio [OR] = 3.1; 95% confidence interval [CI] = 1.8-5.3). No significant associations were seen with total calories from food, number of meals eaten per day, level of fat intake, or consumption of coffee and tea. Risks were highest for those consuming the least amount of vegetables, with some evidence of a dose response for the subcategories of cruciferous vegetables (P for trend < .001) and vegetables consumed raw (P for trend = .10). A significantly elevated risk was also seen for those consuming the least amount of raw fruit (P for trend = .05). No clear associations were reported for intake of particular micronutrients overall or in supplements, but a significant protective effect was associated with increasing intake of dietary fiber (P for trend = .004). The findings of an increased risk with obesity and decreased risks with intake of raw fruits and vegetables and dietary fiber provide useful directions to pursue in further investigations of this malignancy. The finding with respect to obesity is particularly noteworthy, since it may explain at least a portion of the recent epidemic increases reported in the incidence of this tumor.
Article
The incidence of adenocarcinomas of the esophagus and gastric cardia (ACEGC) has been increasing for the past 10-15 years in the United States. The reason for this increase is unknown. This hospital-based case-control study was conducted to assess the effects of dietary and nutritional factors on the risk of ACECG. A total of 95 incident cases with pathological diagnosis and 132 cancer-free controls were included in the study. Patients were recruited at Memorial Sloan-Kettering Cancer Center from 1 November 1992 to 1 November 1994. Epidemiologic data were collected by a modified National Cancer Institute Health Habits History Questionnaire. Nutritional and dietary factors were analyzed using a logistic regression model. Increased risk of ACEGC was significantly related to higher intake of dietary calories and fat after controlling for several potential confounding factors. Decreased risk of ACEGC was significantly associated with high ingestion of dietary fiber, lutein, niacin, vitamin B6, iron, and zinc. Higher intakes of vitamin A, beta-carotene, vitamin E, folate, phosphorus, and potassium were associated with a decreased risk of the disease, but these were not statistically significant. The study suggests that ACEGC can be preventable through dietary interventions.
Article
Members of the European Network of Cancer Registries (ENCR) provide population-based data on cancer incidence for some countries and regions of Europe. These were supplemented by estimates in order to provide comparable information on cancer incidence and mortality in the 15 member states of the European Union (EU). The estimated numbers of new cases of cancer (excluding nonmelanoma skin cancer) in 1990 were approximately 706,900 in men and 644,200 in women. Approximately 497,500 men and 398,200 women died of cancer in the same year. The main sites of incident cases in men were lung (21%), large bowel (13%), prostate (12%), bladder (7%) and stomach (7%). For women, the predominant sites were breast (28%), large bowel (15%), lung (6%), uterine corpus (5%) and stomach (5%). The overall incidence rates for males were highest in continental Western Europe (France, The Netherlands, Austria, Luxembourg, Belgium, Germany and Italy) while the rates of Greece, Portugal, Sweden, Ireland, Spain, Finland, the U.K. and Denmark were below the average value for the EC. Rates for females were highest in Northern and Western Europe, with the exception of France, which had a relatively low rate for females, in common with Greece, Spain and Portugal. The geographical variations in incidence of the major cancers are discussed in relation to risk factors. The estimates show the substantial burden of cancer in European Union populations, but there are also indications of effects of past preventive measures and there is scope for further intervention. Cancer registries are an important source of information for cancer control since they provide population-based incidence and survival statistics. These, along with mortality data, are required to obtain a full picture of the frequency of cancer and its effects at the population level. Some 44% of the EU population is covered by registries. The European Network of Cancer Registries aims to standardise the information provided by existing registries and to provide practical assistance to those in development.
Article
The incidence of esophageal and gastric cardia adenocarcinoma is, for unknown reasons, increasing dramatically. A weak and inconsistent association between body mass index (BMI) and adenocarcinoma of the esophagus and gastric cardia has been reported. To reexamine the association between BMI and development of adenocarcinoma of the esophagus and gastric cardia. Nationwide, population-based case-control study. Sweden, 1995 through 1997. Patients younger than 80 years of age who had recently received a diagnosis were eligible. Comprehensive organization ensured rapid case ascertainment. Controls were randomly selected from the continuously updated population register. Interviews were conducted with 189 patients with adenocarcinoma of the esophagus and 262 patients with adenocarcinoma of the gastric cardia; for comparison, 167 patients with incident esophageal squamous-cell carcinoma and 820 controls were also interviewed. Odds ratios were determined from BMI and cancer case-control status. Odds ratios estimated the relative risk for the two adenocarcinomas studied and were calculated by multivariate logistic regression with adjustment for potential confounding factors. A strong dose-dependent relation existed between BMI and esophageal adenocarcinoma. The adjusted odds ratio was 7.6 (95% CI, 3.8 to 15.2) among persons in the highest BMI quartile compared with persons in the lowest. Obese persons (persons with a BMI > 30 kg/m2) had an odds ratio of 16.2 (CI, 6.3 to 41.4) compared with the leanest persons (persons with a BMI < 22 kg/m2). The odds ratio for patients with cardia adenocarcinoma was 2.3 (CI, 1.5 to 3.6) in those in the highest BMI quartile compared with those in the lowest BMI quartile and 4.3 (CI, 2.1 to 8.7) among obese persons. Esophageal squamous-cell carcinoma was not associated with BMI. The association between BMI and esophageal adenocarcinoma is strong and is not explained by bias or confounding. The carcinogenic mechanism, however, remains to be clarified. The increasing prevalence of obesity in western countries could be important in understanding the increasing occurrence of this tumor.
Article
Firstly, to determine the demographic and behavioural characteristics of low fruit and vegetable consumers. Secondly, to investigate whether knowledge and attitudes are barriers to consumption of fruit and vegetables. Cross sectional survey: an interviewer administrated questionnaire was used to assess the demographic, knowledge, attitude, and behavioural characteristics of the respondents. England. Random sample of 5553 men and women aged between 16 and 74 years. Response rate 70%. The main demographic characteristics of the respondents identified as low consumers of fruit and vegetables (less than daily consumption of either fruit or vegetables) were age, sex, and smoking status. The adjusted odds ratios were 2.59 for those aged 16-24 years compared with those aged 45-74 years, 2.17 for men compared with women, and 1.77 for current smokers compared with never smokers. The most important knowledge and attitude statements after adjusting for the demographic variables were disagreeing with the statement "healthy foods are enjoyable" (odds ratio 1.90) and agreeing with the statement "I don't really care what I eat" (odds ratio 1.76). The impact of knowledge seemed less important than attitudes about a healthy diet in characterising a low fruit and vegetable consumer. These findings are relevant to future strategies for improving intake of fruit and vegetables, but demonstrate the complexity of interventions required, and the dangers inherent in assuming simplistic relations between psychosocial factors and behaviour.
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