Epidemiologic and clinical research has revealed many risk factors which, taken together, can help estimate a person’s probability of developing this cancer. These include demographic factors, host and lifestyle factors, medications, family history, and genetic markers. IC-RISC™ uses an individual’s risk factor profile to estimate his/her absolute risk of developing EA over the next ten years.
While incidence of this cancer has increased, it is still relatively rare. To put this in perspective, risk of developing EA is displayed in the context of risk of dying from other cancers or from causes such as injury, stroke or heart disease. In this way the tool can help inform discussions between a health provider and patient regarding:
how personal risk of EA fits into the “bigger picture” of health and disease,
whether preventive actions are indicated to possibly reduce risk of EA and other conditions, and
whether additional tests and procedures might be warranted to identify and manage those with high risk profiles.
IC-RISC was developed with support from the National Cancer Institute (K05CA124911).
Rates of esophageal adenocarcinoma (EAC) have increased rapidly in the US and much of western Europe, and five year survival continues to be poor. Prevention and early detection efforts for EAC have focused on identifying persons with EAC precursor state, Barrett’s Esophagus (BE), but the survival benefit has been disappointingly low. Precise risk stratification could improve early identification of individuals who will develop EAC, allowing for such high-risk individuals to be targeted for new and evolving preventive and minimally invasive screening technologies. This underlying issue of efficiency is conceptually similar to the Gini coefficient, a widely accepted method to depict the income distribution of a group to assess wealth inequality. A Lorenz curve plots percentage of wealth against the percentage of the population; perfect wealth distribution would result in a slope of 1 and a Gini coefficient of 0 whereas severe wealth inequity results in higher Gini values closer to 1. Some examples of Gini coefficients are shown in Supplementary Figure 1. In this article, we use relative risks of stratified groups to construct Lorenz curves and quantitively analyze the distribution of EAC burden in the US population, for which a higher Gini coefficient indicates more efficient risk stratification.
Li N, Petrick JL, Steck SE, Bradshaw PT, McClain KM, Niehoff NM, Engel LS, Shaheen NJ, Corley DA, Vaughan TL, Gammon MD
Barrett’s esophagus (BE) is the key precursor lesion of esophageal adenocarcinoma, a lethal cancer that has increased rapidly in westernized countries over the past four decades. Dietary sugar intake has also been increasing over time, and may be associated with these tumors by promoting hyperinsulinemia. The study goal was to examine multiple measures of sugar/starches intake in association with BE. This pooled analysis included 472 BE cases and 492 controls from two similarly conducted case-control studies in the United States. Dietary intake data, collected by study-specific food frequency questionnaires, were harmonized across studies by linking with the University of Minnesota Nutrient Database, and pooled based on study-specific quartiles. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age, sex, race, total energy intake, study indicator, body mass index, frequency of gastro-esophageal reflux, and fruit/vegetable intake. In both studies, intake of sucrose (cases vs. controls, g/day: 36.07 vs. 33.51; 36.80 vs. 35.06, respectively) and added sugar (46.15 vs. 41.01; 44.18 vs. 40.68, respectively) were higher in cases than controls. BE risk was increased 79% and 71%, respectively, for associations comparing the fourth to the first quartile of intake of sucrose (ORQ4vs.Q1 = 1.79, 95% CI = 1.07-3.02, P trend = 0.01) and added sugar (ORQ4vs.Q1 = 1.71, 95% CI = 1.05-2.80, P trend = 0.15). Intake of sweetened desserts/beverages was associated with 71% increase in BE risk (ORQ4vs.Q1 = 1.71, 95% CI = 1.07-2.73, P trend = 0.04). Limiting dietary intake of foods and beverages that are high in added sugar, especially refined table sugar, may reduce the risk of developing BE
Li N, Petrick JL, Steck SE, Bradshaw PT, McClain KM, Niehoff NM, Engel LS, Shaheen NJ, Risch HA, Vaughan TL, Wu A, Gammon MD
Background: During the past 40 years, esophageal/gastric cardia adenocarcinoma (EA/GCA) incidence increased in Westernized countries, but survival remained low. A parallel increase in sugar intake, which may facilitate carcinogenesis by promoting hyperglycaemia, led us to examine sugar/carbohydrate intake in association with EA/GCA incidence and survival.
Methods: We pooled 500 EA cases, 529 GCA cases and 2027 controls from two US population-based case-control studies with cases followed for vital status. Dietary intake, assessed by study-specific food frequency questionnaires, was harmonized and pooled to estimate 12 measures of sugar/carbohydrate intake. Multivariable-adjusted odds ratios (ORs) and hazard ratios [95% confidence intervals (CIs)] were calculated using multinomial logistic regression and Cox proportional hazards regression, respectively.
Results: A incidence was increased by 51-58% in association with sucrose (ORQ5vs.Q1 = 1.51, 95% CI = 1.01-2.27), sweetened desserts/beverages (ORQ5vs.Q1 = 1.55, 95% CI = 1.06-2.27) and the dietary glycaemic index (ORQ5vs.Q1 = 1.58, 95% CI = 1.13-2.21). Body mass index (BMI) and gastro-esophageal reflux disease (GERD) modified these associations (Pmultiplicative-interaction ? 0.05). For associations with sucrose and sweetened desserts/beverages, respectively, the OR was elevated for BMI < 25 (ORQ4-5vs.Q1-3 = 1.79, 95% CI = 1.26-2.56 and ORQ4-5vs.Q1-3 = 1.45, 95% CI = 1.03-2.06), but not BMI ? 25 (ORQ4-5vs.Q1-3 = 1.05, 95% CI = 0.76-1.44 and ORQ4-5vs.Q1-3 = 0.85, 95% CI = 0.62-1.16). The EA-glycaemic index association was elevated for BMI ? 25 (ORQ4-5vs.Q1-3 = 1.38, 95% CI = 1.03-1.85), but not BMI < 25 (ORQ4-5vs.Q1-3 = 0.88, 95% CI = 0.62-1.24). The sucrose-EA association OR for GERD < weekly was 1.58 (95% CI = 1.16-2.14), but for GERD ? weekly was 1.01 (95% CI = 0.70-1.47). Sugar/carbohydrate measures were not associated with GCA incidence or EA/GCA survival.
Conclusions: If confirmed, limiting intake of sucrose (e.g. table sugar), sweetened desserts/beverages, and foods that contribute to a high glycaemic index, may be plausible EA risk reduction strategies.
We have recently gained unprecedented insight into genetic factors that determine risk for Barrett’s esophagus (BE) and progression to esophageal adenocarcinoma (EA). Next-generation sequencing technologies have allowed us to identify somatic mutations that initiate BE and track genetic changes during development of tumors and invasive cancer. These technologies led to identification of mechanisms of tumorigenesis that challenge the current multistep model of progression to EA. Newer, cost-effective technologies create opportunities to rapidly translate the analysis of DNA into tools that can identify patients with BE at high risk for cancer, detect dysplastic lesions more reliably, and uncover mechanisms of carcinogenesis.
Liu Z, Chang ET, Liu Q, Cai Y, Zhang Z, Chen G, Huang QH, Xie SH, Cao SM, Shao JY, Jia WH, Zheng Y, Liao J, Chen Y, Lin L, Liang L, Ernberg I, Vaughan TL, Adami HO, Huang G, Zeng Y, Zeng YX, Ye W
BACKGROUND: To the authors’ knowledge, no studies to date have explored familial risks of nasopharyngeal carcinoma (NPC) in detail and quantified its lifetime risk in high-incidence populations.
METHODS: The authors conducted a population-based case-control study of 2499 NPC cases and 2576 controls randomly selected in southern China from 2010 through 2014. Unconditional logistic regression was used to estimate multivariable-adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) associated with a family history of NPC. In addition, the authors compiled a reconstructed cohort comprising 40,781 first-degree relatives of cases and controls to calculate the lifetime cumulative risk of NPC.
RESULTS: Individuals with a first-degree family history of NPC were found to be at a >4-fold risk of NPC (OR, 4.6; 95% CI, 3.5-6.1) compared with those without such a history, but had no excess risk of other malignancies. The excess risk was higher for a maternal than a paternal history and was slightly stronger for a sibling compared with a parental history, and for a sororal than a fraternal history. Among relatives of cases, the cumulative risk of NPC up to age 74 years was 3.7% (95% CI, 3.3%-4.2%), whereas that among relatives of controls was 0.9% (95% CI, 0.7%-1.2%). Cumulative risk was higher in siblings than in parents among relatives of cases, whereas no such difference was noted among relatives of controls.
Thrift AP, Vaughan TL, Anderson LA, Whiteman DC, El-Serag HB.
Barrett’s esophagus (BE) is a premalignant lesion for esophageal adenocarcinoma, a rapidly increasing, highly fatal cancer.1 Clinical guidelines recommend screening for BE in those with chronic gastroesophageal reflux disease (GERD) and at least 2 risk factors (eg, >50 years of age, white race, obese, tobacco smoking history).2,3 However, providing clinicians with a tool that allows them to estimate a patients’ risk may better aid them in deciding who to screen for BE and make future resource utilization more efficient. The Michigan Barrett’s Esophagus pREdiction Tool (M-BERET) predicts risk for BE in men attending primary care using information on their frequency of GERD symptoms, age, waist-to-hip ratio (WHR), and pack-years of cigarette smoking.4 In internal validation, the M-BERET discriminated reasonably well between men with and without BE, with an area under the receiver-operating characteristic curve (AUROC) of 0.72. This was significantly better than using GERD symptoms alone (0.72 vs 0.61; P < .001).4 However, this prediction tool needs to be validated in an independent population before its use can be recommended in clinical practice.
INTRODUCTION/OBJECTIVES: Incidence of esophageal adenocarcinoma (EA), an often fatal cancer, has increased sharply over recent decades. Several important risk factors (reflux, obesity, smoking) have been identified for EA and its precursor, Barrett’s esophagus (BE), but a key challenge remains identifying individuals at highest risk, since most with reflux do not develop BE, and most with BE do not progress to cancer. Metabolomics represents an emerging approach for identifying novel biomarkers associated with cancer development.
METHODS: We used targeted liquid chromatography-mass spectrometry (LC-MS) to profile 57 metabolites in 322 serum specimens derived from individuals with gastroesophageal reflux disease (GERD), BE, high-grade dysplasia (HGD), or EA, drawn from two well-annotated epidemiologic parent studies.
RESULTS: Multiple metabolites differed significantly (P<0.05) between BE versus GERD (n=9), and between HGD/EA versus BE (n=4). Several top candidates (FDR q?0.15), including urate, homocysteine, and 3-nitrotyrosine, are linked to inflammatory processes, which may contribute to BE/EA pathogenesis. Multivariate modeling achieved moderate discrimination between HGD/EA and BE (AUC=0.75), with less pronounced separation for BE versus GERD (AUC=0.64).
CONCLUSION: Serum metabolite differences can be detected between individuals with GERD versus BE, and between those with BE versus HGD/EA, and may help differentiate patients at different stages of progression to EA.