Welcome to my research web page. Details on new findings from my research group, grants and interesting tidbits from the broader epidemiology and biostatistics worlds will be highlighted on this home page from time to time. A more detailed description of my current areas of interest, funded projects and publications can be found on the various pages listed in the header. I enjoy photography as a hobby and have included a link to my gallery for those interested in such things. Thanks for visiting!
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).
This is a beta version, so give it a try — I’d appreciate any feedback:
Clin Gastroenterol Hepatol. 2019 Feb 1. pii: S1542-3565(19)30088-6. doi: 10.1016/j.cgh.2019.01.041. [Epub ahead of print]
No Association Between Vitamin D Status and Risk of Barrett’s Esophagus or Esophageal Adenocarcinoma-a Mendelian Randomization Study.
Dong J, Gharahkhani P, Chow WH, et al.
BACKGROUND & AIMS: Epidemiology studies of circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risk of esophageal adenocarcinoma (EAC) have produced conflicting results. We conducted a Mendelian randomization study to determine the associations between circulating concentrations of 25(OH)D and risks of EAC and its precursor, Barrett’s esophagus (BE).
METHODS: We conducted a Mendelian randomization study using a 2-sample (summary data) approach. Six single-nucleotide polymorphisms (SNPs; rs3755967, rs10741657, rs12785878, rs10745742, rs8018720, and rs17216707) associated with circulating concentrations of 25(OH)D were used as instrumental variables. We collected data from 6167 patients with BE, 4112 patients with EAC, and 17,159 individuals without BE or EAC (controls) participating in the Barrett’s and Esophageal Adenocarcinoma Consortium, as well as studies from Bonn, Germany and Cambridge and Oxford, United Kingdom. Analyses were performed separately for BE and EAC.
RESULTS: Overall, we found no evidence for an association between genetically estimated 25(OH)D concentration and risk of BE or EAC. The odds ratio (OR) per 20 nmol/L increase in genetically estimated 25(OH)D concentration for BE risk estimated by combining the individual SNP association using inverse variance weighting was 1.21 (95% CI, 0.77-1.92; P=.41). The OR for EAC risk, estimated by combining the individual SNP association using inverse variance weighting, was 0.68 (95% CI, 0.39-1.19; P=.18).
CONCLUSIONS: In a Mendelian randomization study, we found that low genetically estimated 25(OH)D concentrations were not associated with risk of BE or EAC.
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.
Communications Biology 2018 Oct 24;1:174.
doi: 10.1038/s42003-018-0182-8. eCollection 2018
Whole-genome sequencing of esophageal adenocarcinoma in Chinese patients reveals distinct mutational signatures and genomic alterations
James Y. Dai, Xiaoyu Wang, Matthew F. Buas, et al
While the incidence of esophageal adenocarcinoma (EAC) has risen drastically in Western countries over the last 40 years, a similar trend has not been observed for EAC in China. Here, we analyzed mutational spectrum, copy number alterations, and structural variants from whole-genome sequencing of 10 Chinese EAC tumor samples and their matched normal samples, and compared them to previously reported EAC tumor specimens from Western countries. The mutational burden in Chinese EAC was significantly lower than that found in EAC from Western countries. The hallmark A>C mutational signature observed at high frequency in EAC from Western countries, which has been linked to acid reflux, is completely absent in Chinese samples. Furthermore, none of the Chinese samples showed evidence of chromothripsis and genome doubling that are often found in EAC from Western countries. In summary, Chinese EAC tumor samples had distinct genomic profiles and signatures, suggesting that EAC in Chinese individuals may arise from a different etiological pathway.
Clin. Gastroenterol. Hepatol. (2018). doi:10.1016/j.cgh.2018.05.002
Lorenz Curves and Gini Coefficient Analyses Indicate Inefficiencies in Esophageal Adenocarcinoma Screening.
Hur C, Zhan T, Thrift AP, Vaughan TL & Feuer, EJ
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.
Eur J Epidemiol. 2017 Nov;32(11):1007-1017
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
Int J Epidem. 2017 Dec 1;46(6):1836-1846
A pooled analysis of dietary sugar/carbohydrate intake and esophageal and gastric cardia adenocarcinoma incidence and survival in the United States (US).
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.
Gastroenterology. 2017 Sep;153(3):657-673
Contino G, Vaughan TL, Whiteman D, Fitzgerald RC
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.