Exploring the Etiology of Esophageal Squamous Cell Carcinoma in the Cohort Consortium
Principal Investigator
Name
Gwen Murphy
Degrees
B.A, Ph.D, M.P.H
Institution
Imperial College London
Position Title
Deputy Head, Cancer Screening and Prevention Research Group
Email
About this CDAS Project
Study
PLCO
(Learn more about this study)
Project ID
PLCO-1818
Initial CDAS Request Approval
Feb 12, 2025
Title
Exploring the Etiology of Esophageal Squamous Cell Carcinoma in the Cohort Consortium
Summary
Esophageal cancer is the eighth most common cancer worldwide and the sixth most common cause of cancer death. Esophageal squamous cell carcinoma (ESCC) comprises 85% of all esophageal cancer cases worldwide. The global distribution of ESCC is extremely uneven, with regions of high incidence across Asia and east Africa, and through South America.
ESCC is often rapidly fatal due to late stage at presentation. Five-year survival rates for esophageal cancer in the USA are close to 20%, 12% in Europe but less than 5% in low resource settings. Screening for early ESCC lesions has been successful in China but it is not feasible in other high incidence regions. Preventing ESCC in regions of extraordinary incidence will require an understanding of risk factors.
In low incidence regions, alcohol and tobacco are strong risk factors for ESCC, but well powered contemporary studies of these risk factors are rare. Factors like diet and air pollution appear to be universal risk factors. Substantial and unexplained disparities by sex, socioeconomic position and race/ethnicity have been reported for ESCC incidence and prognosis. There is significant variation in the male-to-female incidence ratio of ESCC; 1.2:1 in northern Africa and western Asia but 7.8:1 in eastern Europe. This sex ratio has limited what we can learn about ESCC risk factors in women in any single analysis.
Lower socioeconomic position is a consistent risk factor. The burden of ESCC also tends to be highest in black communities and lowest in white communities. While ESCC incidence is declining in the UK and USA, it is not yet known whether these declines affect all social groups or whether disparities persist.
We are planning a cohort consortium analysis to address the following research questions.
Research Questions
1. Are tobacco smoking and alcohol drinking defined by socioeconomic position in driving ESCC risk?
It is widely assumed that socioeconomic position may act as a risk factor by defining exposure to tobacco and alcohol, but previous studies have been underpowered to assess this in combinatorial analyses.
2. Can we define the aspects of poor diet that are associated with higher ESCC risk?
Additional, poorly defined factors (beyond fruit and vegetable intake) may contribute to risk. In high incidence areas, dietary deficiencies) or excesses significantly determine risk of ESCC. In low incidence settings, the contribution of diet is not well defined.
Required Outcome Data: Incident ESCC and EAC ; or mortality from ESCC and EAC.
Required Exposure Data: Tobacco, alcohol, comorbidities, self-reported health, family history of cancer, physical activity, dietary variables and anthropometry, socioeconomic position (income where available, relevant small area statistics, education and occupation).
Required Covariate Data: age, sex, race/ethnicity, comorbidities (diabetes, asthma, hypertension/blood pressure), body mass index, waist-to-hip ratio, baseline lab measurement (CBC, lipid panel, CRP, fasting glucose etc) if available and any existing measurements relating to inflammation or metabolism.
ESCC is often rapidly fatal due to late stage at presentation. Five-year survival rates for esophageal cancer in the USA are close to 20%, 12% in Europe but less than 5% in low resource settings. Screening for early ESCC lesions has been successful in China but it is not feasible in other high incidence regions. Preventing ESCC in regions of extraordinary incidence will require an understanding of risk factors.
In low incidence regions, alcohol and tobacco are strong risk factors for ESCC, but well powered contemporary studies of these risk factors are rare. Factors like diet and air pollution appear to be universal risk factors. Substantial and unexplained disparities by sex, socioeconomic position and race/ethnicity have been reported for ESCC incidence and prognosis. There is significant variation in the male-to-female incidence ratio of ESCC; 1.2:1 in northern Africa and western Asia but 7.8:1 in eastern Europe. This sex ratio has limited what we can learn about ESCC risk factors in women in any single analysis.
Lower socioeconomic position is a consistent risk factor. The burden of ESCC also tends to be highest in black communities and lowest in white communities. While ESCC incidence is declining in the UK and USA, it is not yet known whether these declines affect all social groups or whether disparities persist.
We are planning a cohort consortium analysis to address the following research questions.
Research Questions
1. Are tobacco smoking and alcohol drinking defined by socioeconomic position in driving ESCC risk?
It is widely assumed that socioeconomic position may act as a risk factor by defining exposure to tobacco and alcohol, but previous studies have been underpowered to assess this in combinatorial analyses.
2. Can we define the aspects of poor diet that are associated with higher ESCC risk?
Additional, poorly defined factors (beyond fruit and vegetable intake) may contribute to risk. In high incidence areas, dietary deficiencies) or excesses significantly determine risk of ESCC. In low incidence settings, the contribution of diet is not well defined.
Required Outcome Data: Incident ESCC and EAC ; or mortality from ESCC and EAC.
Required Exposure Data: Tobacco, alcohol, comorbidities, self-reported health, family history of cancer, physical activity, dietary variables and anthropometry, socioeconomic position (income where available, relevant small area statistics, education and occupation).
Required Covariate Data: age, sex, race/ethnicity, comorbidities (diabetes, asthma, hypertension/blood pressure), body mass index, waist-to-hip ratio, baseline lab measurement (CBC, lipid panel, CRP, fasting glucose etc) if available and any existing measurements relating to inflammation or metabolism.
Aims
1) To investigate how known risk factors (smoking, alcohol and poor diet) for ESCC are influenced by age, sex, race/ethnicity and socioeconomic position.
2) Explore how diet, lifestyle and the environment relate to ESCC risk.
3) To investigate whether ESCC risk is associated with a metabolic/inflammatory profile and possible variations in this profile by risk factor and/or social group.
Collaborators
Professor Amanda J Cross, Imperial College London