Content uploaded by Simon Iain Hay
Author content
All content in this area was uploaded by Simon Iain Hay on Apr 02, 2020
Content may be subject to copyright.
www.thelancet.com/gastrohep Published online April 1, 2020 https://doi.org/10.1016/S2468-1253(20)30007-8
1
Articles
Lancet Gastroenterol Hepatol
2020
Published Online
April 1, 2020
https://doi.org/10.1016/
S2468-1253(20)30007-8
See Online/Comment
https://doi.org/10.1016/
S2468-1253(20)30047-9
*Collaborators are listed at the
end of the Article
Correspondence to:
Prof Mohsen Naghavi, Institute
for Health Metrics and
Evaluation, University of
Washington, Seattle, WA 98121,
USA
nagham@uw.edu
or
Prof Reza Malekzadeh, Digestive
Disease Research Institute,
Tehran University of Medical
Sciences, Tehran, Iran
malek@tums.ac.ar
The global, regional, and national burden of oesophageal
cancer and its attributable risk factors in 195 countries and
territories, 1990–2017: a systematic analysis for the Global
Burden of Disease Study 2017
GBD 2017 Oesophageal Cancer Collaborators*
Summary
Background Oesophageal cancer is a common and often fatal cancer that has two main histological subtypes:
oesophageal squamous cell carcinoma and oesophageal adenocarcinoma. Updated statistics on the incidence and
mortality of oesophageal cancer, and on the disability-adjusted life-years (DALYs) caused by the disease, can assist
policy makers in allocating resources for prevention, treatment, and care of oesophageal cancer. We report the latest
estimates of these statistics for 195 countries and territories between 1990 and 2017, by age, sex, and Socio-demographic
Index (SDI), using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD).
Methods We used data from vital registration systems, vital registration-samples, verbal autopsy records, and cancer
registries, combined with relevant modelling, to estimate the mortality, incidence, and burden of oesophageal cancer
from 1990 to 2017. Mortality-to-incidence ratios (MIRs) were estimated and fed into a Cause of Death Ensemble
model (CODEm) including risk factors. MIRs were used for mortality and non-fatal modelling. Estimates of DALYs
attributable to the main risk factors of oesophageal cancer available in GBD were also calculated. The proportion of
oesophageal squamous cell carcinoma to all oesophageal cancers was extracted by use of publicly available data, and
its variation was examined against SDI, the Healthcare Access and Quality (HAQ) Index, and available risk factors in
GBD that are specific for oesophageal squamous cell carcinoma (eg, unimproved water source and indoor air
pollution) and for oesophageal adenocarcinoma (gastro-oesophageal reflux disease).
Findings There were 473 000 (95% uncertainty interval [95% UI] 459 000–485 000) new cases of oesophageal cancer
and 436 000 (425 000–448 000) deaths due to oesophageal cancer in 2017. Age-standardised incidence was 5·9 (5·7–6·1)
per 100 000 population and age-standardised mortality was 5·5 (5·3–5·6) per 100 000. Oesophageal cancer caused
9·78 million (9·53–10·03) DALYs, with an age-standardised rate of 120 (117–123) per 100 000 population. Between
1990 and 2017, age-standardised incidence decreased by 22·0% (18·6–25·2), mortality decreased by 29·0%
(25·8–32·0), and DALYs decreased by 33·4% (30·4–36·1) globally. However, as a result of population growth and
ageing, the total number of new cases increased by 52·3% (45·9–58·9), from 310 000 (300 000–322 000) to 473 000
(459 000–485 000); the number of deaths increased by 40·0% (34·1–46·3), from 311 000 (301 000–323 000) to 436 000
(425 000–448 000); and total DALYs increased by 27·4% (22·1–33·1), from 7·68 million (7·42–7·97) to 9·78 million
(9·53–10·03). At the national level, China had the highest number of incident cases (235 000 [223 000–246 000]),
deaths (213 000 [203 000–223 000]), and DALYs (4·46 million [4·25–4·69]) in 2017. The highest national-level age-
standardised incidence rates in 2017 were observed in Malawi (23·0 [19·4–26·5] per 100 000 population) and Mongolia
(18·5 [16·4–20·8] per 100 000). In 2017, age-standardised incidence was 2·7 times higher, mortality 2·9 times higher,
and DALYs 3·0 times higher in males than in females. In 2017, a substantial proportion of oesophageal cancer DALYs
were attributable to known risk factors: tobacco smoking (39·0% [35·5–42·2]), alcohol consumption (33·8%
[27·3–39·9]), high BMI (19·5% [6·3–36·0]), a diet low in fruits (19·1% [4·2–34·6]), and use of chewing tobacco
(7·5% [5·2–9·6]). Countries with a low SDI and HAQ Index and high levels of indoor air pollution had a higher
proportion of oesophageal squamous cell carcinoma to all oesophageal cancer cases than did countries with a high
SDI and HAQ Index and with low levels of indoor air pollution.
Interpretation Despite reductions in age-standardised incidence and mortality rates, oesophageal cancer remains a
major cause of cancer mortality and burden across the world. Oesophageal cancer is a highly fatal disease, requiring
increased primary prevention eorts and, possibly, screening in some high-risk areas. Substantial variation exists in
age-standardised incidence rates across regions and countries, for reasons that are unclear.
Funding Bill & Melinda Gates Foundation.
Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0
license.
Articles
2
www.thelancet.com/gastrohep Published online April 1, 2020 https://doi.org/10.1016/S2468-1253(20)30007-8
Introduction
Oesophageal cancer is one of the leading causes of
cancer mortality worldwide.1–3 Together with other forms
of gastrointestinal cancers, such as stomach cancer,
colorectal cancer, pancreatic cancer, and hepatocellular
carcinoma, oesophageal cancer causes approximately a
third of all disability-adjusted life-years (DALYs) due to
cancer.1,3
Previous publications have reported on various health
metrics of oesophageal cancer, including its incidence,
mortality, and DALY rates, as well as its risk factors.3
Some of these studies have presented comprehensive
global data for all cancers combined and more sparse
data for each individual cancer.1–3 Others have provided
more detailed data about oesophageal cancer for a certain
country or region,4,5 or used global data that were several
years old and did not have information about DALYs.6,7
We provide, to the best of our knowledge, the first set of
updated estimates about a wide range of oesophageal
cancer health measures at global, regional, and country-
specific levels for 195 countries and territories.
There are two main histological subtypes of oesophageal
cancer: oesophageal adenocarcinoma (which is linked to
obesity, smoking, and gastro-oesophageal reflux disease)
and oesophageal squamous cell carcinoma (which is
linked to alcohol and tobacco consumption). Although
several high-risk regions for oesophageal squamous cell
carcinoma are adjacent to regions with medium or low
risk, such a pattern has not been observed for oesophageal
adenocarcinoma. Globally, more than 85% of all incident
oesophageal cancer cases are oesophageal squamous cell
carcinoma.8
In this analysis of data from the Global Burden of
Diseases, Injuries, and Risk Factors Study (GBD) 2017, we
present estimates of the number of incident cases and
deaths, as well as age-standardised incidence, mortality,
and DALY rates for oesophageal cancer from 1990 to 2017,
by age and sex, for 195 countries and territories.
Furthermore, we provide age-standardised DALYs by
Socio-demographic Index (SDI). Finally, we provide
estimates of the proportion of DALYs attributable to
several major oesophageal cancer risk factors, including
tobacco smoking and chewing, alcohol consumption, low
intake of fruits, and high body-mass index (BMI). Through
this comprehensive evaluation of global oesophageal
cancer measures, we hope to provide additional infor-
mation for policy makers, funding agencies, and
researchers, so they can develop strategies to help prevent
and treat oesophageal cancer in high-risk locations,
determine allocation of scarce health resources, and guide
the direction of future research on oesophageal cancer.
Methods
Overview
This study is part of GBD 2017, which includes estimates
for 195 countries and territories, 21 regions, and
Research in context
Evidence before this study
Oesophageal cancer is one of the leading causes of cancer
mortality worldwide. Previous publications have reported on
various health metrics of oesophageal cancer, but to our
knowledge, no study has provided detailed estimates of
incidence, mortality, disability-adjusted life-years (DALYs), and
DALYs attributable to major risk factors for 195 countries and
territories around the world. Furthermore, previous studies
have not investigated the country-level correlation between
the proportion of new oesophageal squamous cell carcinoma to
all oesophageal cancer cases and potential risk factors for
oesophageal squamous cell carcinoma, such as indoor air
pollution and inadequate access to improved water sources.
Added value of this study
We used data from the Global Burden of Diseases, Injuries, and
Risk Factors Study (GBD) 2017 to provide the most up-to-date
estimates on a wide range of health measures related to
oesophageal cancer at global, regional, and country-specific
levels for 195 countries and territories, and by sex, age group,
and Socio-demographic Index (SDI). We present estimated
numbers and age-standardised incidence rates for oesophageal
cancer in 2017, as well as trends from 1990 to 2017. We also
describe DALYs attributed to several major risk factors for
oesophageal cancer. Furthermore, for the first time, we present
the correlation of the country-level proportion of new
oesophageal squamous cell carcinoma to all oesophageal
cancer cases with several potential risk factors for oesophageal
squamous cell carcinoma, including indoor air pollution,
inadequate access to improved water sources, and SDI. These
correlations can guide further investigations into the causes of
oesophageal squamous cell carcinoma.
Implications of all the available evidence
Oesophageal cancer remains a major cause of cancer mortality
and disease burden across the world, requiring substantial
preventive measures and possibly screening by use of upper
gastrointestinal endoscopy in certain high-risk countries.
The highest burden of oesophageal cancer (in terms of the
number of DALYs) is in east Asia, particularly China, where
screening has been shown to be effective in increasing survival
rates. Other high-incidence regions are in central Asia and
sub-Saharan Africa. The main reasons for these high rates are
unknown. Further research into the causes of oesophageal
cancer in these high-risk areas is warranted. Our findings are
consistent with previous studies that suggest indoor air
pollution, inadequate access to improved water sources, and
low socioeconomic status are associated with increased risk of
oesophageal squamous cell carcinoma. Several epidemiological
studies are ongoing by different research groups, and we expect
to see new findings over the next few years.
Articles
www.thelancet.com/gastrohep Published online April 1, 2020 https://doi.org/10.1016/S2468-1253(20)30007-8
3
seven super-regions. GBD 2017 presented estimates for
359 diseases and injuries; 282 causes of death; and
84 behavioural, environmental, occupational, and
metabolic risk factors. The methodology used to collect
data for this research has been discussed previously.9–12
Rates per 100 000 population were age-standardised
according to the GBD world population.13 95% uncertainty
intervals (95% UIs) were reported for estimates, including
for sources of uncertainty arising from measurement
error, potential biases, and modelling. Statistical analyses
were done with Python (version 2.7.14), R (version 3.3.2),
and Stata (release 15) software. This study is compliant
with the Guidelines for Accurate and Transparent Health
Estimates Reporting (GATHER) statement.
Data and estimation framework
Data came from vital registration systems (19 323 site-
years), vital registration-samples (793 site-years), verbal
autopsy records (419 site-years), and cancer registries
(5497 site-years).9 Of these, only cancer registries had
both mortality and incidence data, whereas vital registries
and verbal autopsies had only mortality data. By use of
International Classification of Diseases 10 (ICD-10)
codes,10 all cancers coded as C15.0-C15.9, D00.1, and
D13.0 were considered to be oesophageal cancer. Four
sequelae and associated disability weights were used,
including diagnosis, controlled, metastatic, and terminal
phases (appendix p 9).10 Disability weights ranged from
0 (perfect health) to 1 (equivalent to death).
Mortality modelling
Some locations had high-quality incidence and mortality
cancer registry data, whereas data were sparse in other
locations.9 Therefore, incidence and mortality estimates
were obtained with a combination of available data and
modelling. We first estimated mortality-to-incidence
ratios (MIRs) using sources that had accurate incidence
and mortality data for the same year. MIRs were estimated
for other locations by use of a linear-step mixed-eects
model with logit link functions, with the Healthcare
Access and Quality (HAQ) Index, age, and sex as
covariates. The resulting estimates were then smoothed
over space and time and adjusted with spatiotemporal
Gaussian process regression.14 Estimated mortality data
for each site were obtained by multiplying incidence data
by MIRs. As the next step, both observed and estimated
mortality data were fed into a Cause of Death Ensemble
model (CODEm), along with the mortality data from vital
registration and verbal autopsy.9 The covariates included
in CODEm that were assumed to have a positive
relationship with oesophageal cancer mortality were
smoking prevalence, tobacco consumption (cigarettes per
capita), mean BMI, log-transformed age-standardised
summary exposure value scalar for oesophageal cancer,
alcohol (L per person), and indoor air pollution
(prevalence of households cooking with coal or biomass).
The covariates included in the CODEm that were
assumed to have a negative relationship with oesophageal
cancer were fruit intake, adjusted (g); improved water
source (proportion with access); HAQ Index; vegetable
intake, adjusted (g); sanitation (proportion with access);
and education (years per person). Finally, the covariates
included in the CODEm that had no prior assumptions
about the direction of the relationship were lag-distributed
income (international dollar [Int$] per person) and SDI.
All the covariates had a plausible association with
oesophageal cancer deaths based on the published
literature, although evidence of causality was not required
for their inclusion in the model.12,15
Non-fatal modelling
The final mortality estimates were obtained from
CoDCorrect,9 with modelling described above, and were
divided by the MIR to compute oesophageal cancer
incidence. The prevalence of oesophageal cancer was
calculated by modelling survival for each incidence cohort
by using the MIR as a scalar and adjusting for expected
background mortality.10 The cohort members who had
survived more than 10 years were assumed to be cured,
and these cases were divided into two sequelae: the
diagnosis and primary therapy phase and the controlled
phase. Furthermore, the prevalence for the cohort that
died during the 10-year period was categorised into four
sequelae (appendix p 9). A time duration of 5 months was
used to define the diagnosis and primary therapy phase,16
4·6 months used to define the metastatic phase,17 and
1 month used to define the terminal phase. The remaining
time was assigned to the controlled phase.
Following this process, each sequela-specific prevalence
rate was multiplied by a sequela-specific disability weight
to estimate the sequelae-specific years lived with disability
(YLDs). DALYs were calculated as the sum years of life
lost (YLLs) due to premature death and YLDs.
Socio-demographic Index (SDI)
SDI was used in this study to determine the relationship of
a country’s socioeconomic development status with age-
standardised incidence and mortality rates for oesophageal
cancer. In GBD 2017, SDI was revised to better reflect the
development status of each country.9–11 SDI ranges from
0 (worst) to 1 (best) and is composed of the total fertility
rate under the age of 25 years, mean education for those
aged 15 years and older, and lag-distributed income per
capita.13 The HAQ Index determines the personal access to
and quality of health care for 195 countries and territories
and is calculated on the basis of amenable mortality, or
deaths from causes that should not occur in the presence
of eective medical care. The HAQ Index ranges from
0 (worst) to 100 (best). More details about the HAQ Index
are presented in previous publications.18
Risk factors
We calculated and reported the percentage of DALYs due
to oesophageal cancer that were attributable to smoking,
See Online for appendix
Articles
4
www.thelancet.com/gastrohep Published online April 1, 2020 https://doi.org/10.1016/S2468-1253(20)30007-8
alcohol use, high BMI, a diet low in fruits, and chewing
tobacco (established oesophageal cancer risk factors with
available data in GBD). Details about the definitions of
these risk factors and their relative risk for oesophageal
cancer are described elsewhere.12
Publicly available data for the two main histological
subtypes of oesophageal cancer (ie, oesophageal
squamous cell carcinoma and oesophageal adeno-
carcinoma) were obtained from Cancer Incidence in
Five Continents (Vol XI).7 Local cancer registries from
151 countries provided data about the incidence of
oesophageal squamous cell carcinoma, oesophageal
adenocarcinoma, and all oesophageal cancer. The
proportion of the incidence of oesophageal squamous
cell carcinoma out of all oesophageal cancer cases was
calculated for each country and territory and linked to
GBD estimates using country codes. We regressed the
proportion of oesophageal squamous cell carcinoma to
all oesophageal cancer cases (as a continuous response
variable) against SDI and the HAQ Index, and against
risk factors for oesophageal squamous cell carcinoma
(percentage of the population with access to improved
water sources, and prevalence of households cooking
with coal or biomass [indoor air pollution]) and
oesophageal adenocarcinoma (gastro-oesophageal reflux
disease).
Role of the funding source
The funder of the study had no role in study design, data
collection, data analysis, data interpretation, or the
writing of the report. All authors had full access to the
data in the study and had final responsibility for the
decision to submit for publication.
Results
In 2017, there were 473 000 (95% UI 459 000–485 000) new
cases of oesophageal cancer and 436 000 (425 000–448 000)
deaths due to oesophageal cancer. Age-standardised
incidence was 5·9 (5·7–6·1) per 100 000 population and
the age-standardised mortality rate was 5·5 (5·3–5·6) per
100 000 population. 9·78 million (9·53–10·03) DALYs
were due to oesophageal cancer, with an age-standardised
rate of 119·9 (116·9–123·0) per 100 000 population
(appendix pp 10–33).
Between 1990 and 2017, global age-standardised
incidence decreased by 22·0% (95% UI 18·6–25·2),
mortality decreased by 29·0% (25·8–32·0), and DALYs
decreased by 33·4% (30·4–36·1; appendix pp 10–33).
However, during the same period, the total number of
new cases increased by 52·3% (45·9–58·9), from 310 000
(301 000–322 000) to 473 000 (459 000–485 000); the
number of deaths increased by 40·0% (34·1–46·3), from
311 000 (301 000–323 000) to 436 000 (425 000–448 000);
and total DALYs increased by 27·4% (22·1–33·1), from
7·68 million (7·42–7·97) to 9·78 million (9·53–10·03;
appendix pp 2, 10–33).
From among 21 GBD regions, in 2017, the highest age-
standardised incidence rates were in east Asia
(12·1 [95% UI 11·5–12·7] per 100 000 population),
southern sub-Saharan Africa (10·0 [9·5–10·4] per
100 000 population), eastern sub-Saharan Africa (7·8
[7·2–8·6] per 100 000 population), central sub-Saharan
Africa (7·3 [6·2–8·5] per 100 000 population), and central
Asia (5·7 [5·4–5·9]; figure 1A, appendix pp 10–17). In 2017,
the highest regional age-standardised incidence rate
(12·1 per 100 000 population in east Asia) was 9·3 times
higher than the lowest (1·3 [1·2–1·4] per 100 000 population
in Andean Latin America; appendix pp 10–17). With some
minor change in rank order, regions with high age-
Figure 1: The age-standardised incidence (A) and death rates (B) of oesophageal cancer in 2017 for 21 GBD
regions, by sex
GBD=Global Burden of Diseases, Injuries, and Risk Factors Study.
GBD regions
Andean Latin America
Central Latin America
North Africa and Middle East
Oceania
Southeast Asia
Central Europe
Caribbean
South Asia
Western sub-Saharan Africa
High-income North America
Eastern Europe
Western Europe
Southern Latin America
Australasia
Tropical Latin America
High-income Asia Pacific
Central Asia
Central sub-Saharan Africa
Eastern sub-Saharan Africa
Southern sub-Saharan Africa
East Asia
A
0 5 10 15 20
Age-standardised incidence rate per 100
000 population
GBD regions
B
0 5 10 15 20
Age-standardised death rate per 100
000 population
Andean Latin America
Central Latin America
Oceania
North Africa and Middle East
Southeast Asia
Central Europe
Eastern Europe
Caribbean
High-income Asia Pacific
Western Europe
High-income North America
Australasia
South Asia
Western sub-Saharan Africa
Southern Latin America
Tropical Latin America
Central Asia
Central sub-Saharan Africa
Eastern sub-Saharan Africa
East Asia
Southern sub-Saharan Africa
Male
Female
Articles
www.thelancet.com/gastrohep Published online April 1, 2020 https://doi.org/10.1016/S2468-1253(20)30007-8
5
Figure 2: Age-standardised incidence (A) and death rates (B) of oesophageal cancer per 100 000 population in 2017, by country and territory
ATG=Antigua and Barbuda. VCT=Saint Vincent and the Grenadines. LCA=Saint Lucia. TTO=Trinidad and Tobago. Isl=Islands. FSM=Federated States of Micronesia. TLS=Timor-Leste.
A
B
Persian Gulf
Caribbean LCA
Dominica
ATG
TTO
Grenada
VCT
TLS
Maldives
Barbados
Seychelles
Mauritius
Comoros
West Africa Eastern
Mediterranean
Malta
Singapore Balkan Peninsula Tonga
Samoa
FSM
Fiji
Solomon Isl
Marshall Isl
Vanuatu
Kiribati
Persian Gulf
Caribbean LCA
Dominica
ATG
TTO
Grenada
VCT
TLS
Maldives
Barbados
Seychelles
Mauritius
Comoros
West Africa Eastern
Mediterranean
Malta
Singapore Balkan Peninsula Tonga
Samoa
FSM
Fiji
Solomon Isl
Marshall Isl
Vanuatu
Kiribati
0 to <2
2 to <4
4 to <6
6 to <8
8 to <10
10 to <12
12 to <14
14 to <16
16 to <18
18 to <20
20 to <23
Age-standardised incidence rate
(per 100
000 population), both sexes, 2017
Age-standardised death rate
(per 100
000 population), both sexes, 2017
0 to <2
2 to <4
4 to <6
6 to <8
8 to <10
10 to <12
12 to <14
14 to <16
16 to <18
18 to <20
20 to <22
22 to <24
Articles
6
www.thelancet.com/gastrohep Published online April 1, 2020 https://doi.org/10.1016/S2468-1253(20)30007-8
standardised incidence rates also had the highest age-
standardised mortality and DALY rates (figure 1B,
appendix pp 18–33). Because of the high incidence rates
and its large population, over half of all new cases of
oesophageal cancer in 2017 came from east Asia (245 000
[233 000–256 000] of 473 000 [459 000–485 000] global
incident cases; 51·8%; appendix pp 10–17). By contrast,
the lowest age-standardised incidence, mortality, and
DALY rates were seen in Andean Latin America, central
Latin America, Oceania, north Africa and the Middle East,
and southeast Asia (figure 1, appendix pp 10–33).
Stark dierences were observed in age-standardised
incidence rates of oesophageal cancer between nearby
regions. For example, the age-standardised incidence
rate in southeast Asia, which is close to east Asia, was
low (2·5 [95% UI 2·4–2·7] per 100 000 population in
2017). Similarly, in contrast to the high age-standardised
incidence rate seen in east sub-Saharan Africa
(7·8 [7·2–8·6] per 100 000 population in 2017), the age-
adjusted incidence rate in western sub-Saharan Africa
was low (4·0 [3·5–4·7] per 100 000 population in 2017).
Between 1990 and 2017, the regional age-standardised
incidence, mortality, and DALY rates for oesophageal
cancer decreased in all GBD regions except for high-
income North America for age-standardised incidence
rates (7·4% [95% UI 3·9–11·1]), and western sub-Saharan
Africa for all three measures (percentage change 35·7%
[15·6–58·9] for age-standardised incidence, 37·2%
[17·1–60·3] for age-standardised mortality, and 31·4%
[12·3–55·4] for age-standardised DALYs; appendix pp 3–4,
10–33). The sharpest declines in age-standardised
incidence rates over the study period were seen in central
Asia (55·1% [95% UI 52·5–57·5]), east Asia (36·1%
[31·3–40·9]), southern Latin America (40·9% [34·8–45·7]),
Andean Latin America (33·5% [26·5–40·4]), central Latin
America (32·8% [29·6–36·0]), central sub-Saharan Africa
(30·1% [18·5–41·2]), and eastern sub-Saharan Africa
(27·4% [19·0–34·7]).
At the national level, China had the highest number of
incident cases (235 000 [95% UI 223 000–246 000]), deaths
(213 000 [203 000–223 000]), and DALYs (4·46 million
[4·25–4·69]) in 2017, comprising nearly half of new cases,
deaths, and DALYs globally that year. The highest
estimated national-level age-standardised incidence,
mortality, and DALY rates in 2017 were observed in
certain countries in sub-Saharan Africa (eg, Malawi,
eSwatini, Lesotho, Zimbabwe, and Uganda), central Asia
(eg, Mongolia, Turkmenistan, and Azerbaijan), and east
Asia (eg, China; figure 2; appendix pp 10–33). Malawi
had the highest age-standardised incidence rate
(23·0 [19·4–26·5] per 100 000 population), followed by
Mongolia (18·5 (16·4–20·8) per 100 000 population). In
2017, the ratio of the highest age-standardised incidence
rate to the lowest (0·6 [0·6–0·7] per 100 000 population in
Iraq) was 1. Patterns of age-standardised mortality and
DALY rates closely followed those of age-standardised
incidence rates, which reflects the poor survival of
patients with oesophageal cancer, particularly in low-
income and middle-income countries.
Similar to the global and regional trends, between
1990 and 2017, most countries and territories had a
decrease in age-standardised incidence, mortality, and
DALY rates due to oesophageal cancer (appendix
pp 10–33). For example, age-standardised incidence
rates decreased in Turkmenistan (by 71·9% [95% UI
69·1 to 74·6]), Uzbekistan (by 68·1% [64·1 to 71·7]),
Kazakhstan (by 64·3% [61·4 to 67·2]), Kyrgyzstan (by
55·4% [51·1 to 59·3]), and China (by 36·9%
Figure 3: Global number and age-standardised rates of incidence (A), mortality (B), and DALYs (C) of
oesophageal cancer per 100 000 population by age and sex, 2017
Shading indicates the upper and lower limits of the 95% uncertainty intervals (95% UIs). DALY=disability-adjusted
life-year.
0
200
400
600
800
1000
1200
DALY rate per 100
000 population
0
20
40
60
80
100
Death rate per 100
000 population
0
20
40
60
80
100
Incidence rate per 100
000 population
15–19
20–24
25–29
30–34
35–39
40–44
45–49
50–54
55–59
60–64
65–69
70–74
75–79
80–84
85–89
90–94
≥95
0
200
000
400
000
600
000
800
000
1
000
000
1
200
000
1
400
000
1
600
000
C
Number of DALYs
0
10
000
20
000
30
000
40
000
50
000
60
000
B
Number of deaths
Age (years)
0
10
000
20
000
30
000
40
000
50
000
60
000
70
000
80
000
A
Number of incident cases
Male (number and 95% UI)
Female (number and 95% UI)
Male (rate and 95% UI)
Female (rate and 95% UI)
Articles
www.thelancet.com/gastrohep Published online April 1, 2020 https://doi.org/10.1016/S2468-1253(20)30007-8
7
[32·1 to 41·7]). However, there were clear exceptions to
the overall trend, particularly among high-income
countries. For example, age-standardised incidence
rates increased in the USA (6·7% [95% UI 3·1 to 10·4]),
Canada (10·6% [–0·4 to 23·5]), Austria (23·1%
[9·9 to 38·4]), Germany (38·4% [19·9 to 60·2]), Latvia
(53·3% [28·0 to 81·4]), and the Netherlands (86·6%
[68·2 to 106·6]). Likewise, some countries in western
sub-Saharan Africa, such as Sierra Leone (61·4%
[23·9 to 109·9]), Benin (74·6% [38·9 to 124·2]), and
Chad (84·1% [46·4 to 128·9]), had increased age-
standardised incidence rates. Incidence, mortality, and
DALY rates varied by age, sex, and SDI in 2017.
Incidence and mortality rates started climbing at age 50
years but DALYs started climbing at age 40 years and
dropped in the oldest age groups, as younger age
groups lost more years of life (figure 3). Incidence,
mortality, and DALY rates were also higher in males
than in females in all age groups (figure 3). Age-
standardised incidence rates were 2·7 times higher,
mortality rates 2·9 times higher, and DALY rates
3·0 times higher in males than in females (appendix pp
10–33). Because oesophageal cancer is a highly fatal
disease with a high MIR (0·91), almost all DALYs
(98·7%) were attributable to YLLs due to premature
death (appendix p 5). The observed regional and
national age-standardised DALY rates in relation to
SDI, versus the expected level for each location on the
basis of SDI, are shown in figure 4. The high-income
regions, central and eastern Europe, and tropical and
southern Latin America closely followed expected
trends over the study period. Among many of the
middle SDI regions, however, the observed patterns
varied widely, with some regions staying well below
Figure 4: Age-standardised DALY rates for oesophageal cancer for 21 GBD regions (A) and 195 countries and territories (B) by Socio-demographic Index,
1990–2017
Expected values based on Socio-demographic Index and disease rates in all locations are shown as the black line. DALY=disability-adjusted life-year. GBD=Global
Burden of Diseases, Injuries, and Risk Factors Study.
Global
High-income Asia Pacific
High-income North America
Western Europe
Australasia
Andean Latin America
Tropical Latin America
Central Latin America
Southern Latin America
Caribbean
Eastern Europe
Central Europe
Central Asia
North Africa and Middle East
South Asia
Southeast Asia
East Asia
Oceania
Western sub-Saharan Africa
Eastern sub-Saharan Africa
Central sub-Saharan Africa
Southern sub-Saharan Africa
Luxembourg
Netherlands
Norway
Iceland
Andorra
Finland
Switzerland
Belgium
Sweden
Ireland
Canada
Australia
Singapore
Germany
USA
Austria
Japan
Cyprus
Taiwan
Slovenia
Estonia
Brunei
Italy
UK
New Zealand
Slovakia
Lithuania
Malta
Latvia
Spain
Greece
Israel
Puerto Rico
Virgin Islands
Bermuda
United Arab Emirates
Guam
Russia
Montenegro
Kuwait
Portugal
Belarus
Qatar
Libya
Greenland
Malaysia
The Bahamas
Serbia
Chile
Barbados
Kazakhstan
Lebanon
Turkey
Antigua and Barbuda
Bahrain
Argentina
China
Uruguay
Armenia
American Samoa
Azerbaijan
Iran
Turkmenistan
Seychelles
Cuba
Dominica
Albania
Thailand
Sri Lanka
Jamaica
South Africa
Brazil
Botswana
Mongolia
Venezuela
Saint Lucia
Global
Gabon
Indonesia
Fiji
Suriname
Grenada
Uzbekistan
Equatorial Guinea
Tonga
Paraguay
Philippines
Kyrgyzstan
Egypt
Belize
Bolivia
Iraq
Guyana
Swaziland
Samoa
Federated States of Micronesia
Congo
Bhutan
Myanmar
Marshall Islands
India
Cape Verde
Palestine
North Korea
Nicaragua
Tajikistan
Laos
Honduras
Timor-Leste
Kenya
Nigeria
Lesotho
Pakistan
São Tomé and Príncipe
Djibouti
Cameroon
Cambodia
Sudan
Vanuatu
Zambia
Mauritania
Zimbabwe
Angola
Bangladesh
Haiti
Comoros
Yemen
Nepal
Kiribati
Solomon Islands
Papua New Guinea
Togo
Tanzania
Côte d’Ivoire
Eritrea
Rwanda
The Gambia
Uganda
Benin
Senegal
DR Congo
Sierra Leone
Malawi
Guinea-Bissau
Mozambique
Central African Republic
Ethiopia
Madagascar
Liberia
Guinea
Burundi
Afghanistan
Burkina Faso
South Sudan
Mali
Chad
Somalia
Niger
Peru
Morocco
Denmark
0·30·2 0·4 0·5 0·6 0·7 0·8 0·9
0
100
200
300
400
500
600
B
Age-standardised DALY rate per 100
000 population
0
50
100
150
200
250
300
350
400
450
500
A
Age-standardised DALY rate per 100
000 population
Socio-demographic Index
Articles
8
www.thelancet.com/gastrohep Published online April 1, 2020 https://doi.org/10.1016/S2468-1253(20)30007-8
expected levels throughout the study period with little
change in age-standardised rates and others well above
expected levels but with fluctuating or decreasing age-
standardised rates (figure 4A). In 2017, there was an
inverse association between age-standardised DALY
rates for oesophageal cancer and SDI at the national
level, with some exceptions (figure 4B). Similar patterns
were observed for incidence and mortality in relation-
ship to SDI (appendix p 6).
At the global level, a substantial proportion of DALYs
were attributable to the five risk factors for which GBD
estimates were available, including 39·0% (95% UI
35·5–42·2) attributable to tobacco smoking, 33·8%
(27·3–39·9) to alcohol consumption, 19·5% (6·3–36·0)
to high BMI, 19·1% (4·2–34·6) to a diet low in fruits, and
7·5% (5·2–9·6) to use of chewing tobacco (figure 5). The
impact of these risk factors varied by region. For example,
the impact of smoking was highest in eastern Europe
(53·7% of DALYs were attributable to smoking) and
central Europe (49·8%), where smoking is still prevalent,
and lowest in western sub-Saharan Africa (14·8%).
Likewise, the impact of alcohol consumption was highest
in central Europe (55·8% of DALYs attributable to
alcohol) and eastern Europe (54·3%), and lowest in north
Africa and the Middle East (7·2%), where alcohol
consumption is relatively low.
Clear patterns emerged by generating graphs of the
proportion of oesophageal squamous cell carcinoma to
oesophageal adenocarcinoma cases and to all oesophageal
cancer cases versus SDI, HAQ Index, and household air
pollution, which were obtained by linking to data from
Cancer Incidence in Five Continents (Vol XI; appendix
pp 7, 34–37). At the country level, this proportion was
strongly positively correlated with indoor air pollution,
even after adjustment for SDI, meaning that countries
and territories with worse indoor air pollution had higher
proportions of oesophageal squamous cell carcinoma
from among all oesophageal cancer cases. The proportion
of oesophageal squamous cell carcinoma to all oesophageal
cancer cases was also positively correlated with inadequate
access to improved water sources, but the strength of this
correlation decreased after adjusting for SDI. A higher
proportion of oesophageal squamous cell carcinoma to all
oesophageal cancer cases was inversely correlated with
SDI and the HAQ Index, meaning that countries and
territories higher on the SDI and HAQ Indexes had lower
proportions of oesophageal squamous cell carcinoma
from among all oesophageal cancer cases. No clear pattern
was observed for the association between the proportion
of oesophageal squamous cell carcinoma to all oesophageal
cancer cases versus the prevalence of gastro-oesophageal
reflux disease (appendix p 8).
Figure 5: Proportion of oesophageal cancer DALYs attributable to tobacco smoking and chewing, alcohol use, high BMI, and low intake of fruits, for 21 GBD regions, 2017
BMI=body-mass index. DALY=disability-adjusted life-year. GBD=Global Burden of Diseases, Injuries, and Risk Factors Study.
31·0%
22·2%
19·0%
14·8%
31·7%
46·3%
38·1%
22·4%
26·9%
32·0%
53·8%
49·8%
39·5%
41·0%
27·6
35·0%
22·1%
33·2%
42·5%
39·9%
45·3%
39%
Smoking Alcohol use High BMI Diet low in fruits Chewing tobacco
38·8%
28·4%
26·9%
30·1%
28·0%
36·3%
28·8%
17·5%
7·2%
36·6%
54·3%
55·8%
35·8%
39·2%
40·3%
41·4%
36·3%
52·0%
49·4%
38·5%
29·6%
33·8%
27·3%
13·8%
12·4%
17·2%
20·9%
16·2%
15·0%
14·4%
29·7%
28·4%
30·5%
33·9%
26·9%
29·9%
29·0%
30·1%
26·8%
34·4%
28·6%
38·3%
13·8%
19·5%
24·5%
21·4%
19·5%
20·0%
20·9%
19·9%
18·7%
20·8%
14·3%
21·5%
20·7%
19·5%
10·0%
14·1%
14·3%
11·8%
13·1%
16·0%
15·7%
15·1%
18·1%
19·1%
0·7%
1·7%
3·9%
2·1%
5·1%
5·6%
10·4%
24·8%
9·7%
0·5%
0·2%
0·2%
0·7%
0·2%
0·5%
0·6%
1·0%
2·0%
0·2%
4·6%
2·1%
7·5%
GBD regions
Southern sub-Saharan Africa
Central sub-Saharan Africa
Eastern sub-Saharan Africa
Western sub-Saharan Africa
Oceania
East Asia
Southeast Asia
South Asia
North Africa and Middle East
Central Asia
Eastern Europe
Central Europe
Caribbean
Southern Latin America
Central Latin America
Tropical Latin America
Andean Latin America
Australasia
Western Europe
High-income North America
High-income Asia Pacific
Global
0 10 20 30 40 50 60 0 10 20 30 40 50 60 0 10 20 30 40 50 60 0 10 20 30 40 50 60 0 10 20 30 40 50 60
Proportion of DALYs
attributable to risk factors (%)
Proportion of DALYs
attributable to risk factors (%)
Proportion of DALYs
attributable to risk factors (%)
Proportion of DALYs
attributable to risk factors (%)
Proportion of DALYs
attributable to risk factors (%)
Articles
www.thelancet.com/gastrohep Published online April 1, 2020 https://doi.org/10.1016/S2468-1253(20)30007-8
9
Discussion
The results of GBD 2017 show that the large variations
in age-standardised incidence, mortality, and DALY
rates across countries and territories are still a main
epidemiological feature of oesophageal cancer (with the
majority of cases being oesophageal squamous cell
carcinoma), indicating the importance of finer
delineation of hotspots to specify at-risk populations.
GBD estimates show a decrease in age-adjusted
incidence rates in most parts of the world, particularly
in regions where oesophageal squamous cell carcinoma
is the dominant histological subtype (eg, in central
Asia), but an increase in these rates in regions where
oesophageal adeno carcinoma is the major subtype
(eg, high-income North America), emphasising the
importance of collecting data to dierentiate these
two subtypes. Further investigation is needed of the
causes of the high age-standardised incidence rates
seen in some parts of the world, particularly in high-risk
areas of sub-Saharan Africa, Mongolia, China, and Iran.
The observed global decrease in age-standardised
incidence rate from 1990 to 2017 is perhaps due to
improvements in several social and environmental
factors, such as the SDI.
Our findings add to the literature by providing the most
up-to-date data on a wide range of oesophageal cancer
health metrics, including age-standardised rates of DALYs
for 195 countries and territories, DALYs attributable to
several major risk factors of oesophageal cancer, and
trends of these measures from 1990 to 2017. Although
age-standardised incidence and mortality rates of
oesophageal cancer have decreased at the global level over
the past three decades, absolute numbers of new
oesophageal cancer cases and deaths and DALYs
attributable to oesophageal cancer have increased as a
result of population growth and ageing. These trends
over time indicate that oesophageal cancer still causes a
substantial disease burden across the world, and the
overall burden could continue to rise. Our results
corroborate findings from previous studies but use
dierent sources of data and estimation methods. The
country-level positive correlations between the proportion
of oesophageal squamous cell carcinoma to all
oesophageal cancer cases and high indoor pollution, low
access to improved water sources, low SDI, and low HAQ
Index are novel and support the hypothesis that these
factors could contribute to the risk of oesophageal
squamous cell carcinoma. Gastro-oesophageal reflux
disease, an established risk factor for oesophageal
adenocarcinoma (but not oesophageal squamous cell
carcinoma), showed a U-shaped relationship with the
proportion of oesophageal squamous cell carcinoma to all
oesophageal cancer cases. No clear explanation exists for
this unexpected finding, although we can suggest some
hypotheses. This U-shaped relationship was primarily
due to aberrations seen in eastern Europe, an area that is
close to geographical areas of Asia where oesophageal
squamous cell carcinoma is prevalent, and adjacent to
western Europe, where gastro-oesophageal reflux disease
and oesophageal adenocarcinoma are highly prevalent.
This geographical proximity, combined with spatial
modelling, might have aected the estimates. Another
possibility is a potential association between gastro-
oesophageal reflux disease prevalence and one or more
oesophageal squamous cell carcinoma risk factors in
these regions.
The estimated numbers of new cases of oesophageal
cancer based on GBD estimates were lower than those
estimated with the 2018 Global Cancer Observatory
(GLOBOCAN).2 We estimated 473 000 new cases and
436 000 deaths in 2017 using GBD, versus 572 000 new
cases and 509 000 deaths in GLOBOCAN data. These
discrepancies are due to incomplete data in both datasets
and dierences in modelling. For example, weighting
the data by the level of their completeness in GBD might
give more weight to data from high-income countries,
where data are more complete and oesophageal cancer
incidence rates are low.
Some countries in east and central Asia, as well as in
eastern, central, and southern sub-Saharan Africa, had
high age-standardised incidence, mortality, and DALY
rates over the study period. These findings are consistent
with previous literature. Since at least the early 1970s,
vast areas of Asia, extending from China and Mongolia to
the Caspian Sea, have been known to have high rates of
oesophageal cancer.19 This area, dubbed the so-called
Asian oesophageal cancer belt,19–21 was along the path of
the Silk Road, which has led to hypotheses that some
shared environmental risk or genes passed along this
route were the common causes of the observed high
risks.19,21,22 More than 90% of oesophageal cancer cases in
this part of the world are of the squamous cell type
(oesophageal squamous cell carcinoma).22–24 However,
tobacco and alcohol consumption, which are the major
risk factors for oesophageal squamous cell carcinoma in
many parts of the world, are not strong risk factors in the
Asian oesophageal cancer belt.22,23,25,26 Case-control and
cohort studies have found that opium use, consumption
of hot tea, low intake of fresh fruits and vegetables,
indoor air pollution, exposure to polycyclic aromatic
hydrocarbons, lack of access to piped water, poor oral
health, and low socioeconomic status are also associated
with a higher risk of oesophageal squamous cell
carcinoma.26–32 However, as yet, no single dominant risk
factor has been identified for oesophageal squamous cell
carcinoma in the Asian oesophageal cancer belt. Most
published findings of risk factors for oesophageal cancer
in the Asian oesophageal cancer belt come from studies
done in China and Iran. No recent studies have been
done in Mongolia to address the high incidence and
mortality rates in this population, although several risk
factors are shared with other high-risk areas, such as
high level of fluoride in drinking water or drinking hot
milk tea.33 High rates of oesophageal cancer in eastern,
Articles
10
www.thelancet.com/gastrohep Published online April 1, 2020 https://doi.org/10.1016/S2468-1253(20)30007-8
central, and southern sub-Saharan Africa, an area dubbed
the African oesophageal cancer corridor, are also well
established.34 The majority of cases in this area are also
oesophageal squamous cell carcinoma. Until recently,
few studies had been done to identify risk factors for
oesophageal cancer in this region. Recent studies,
however, have suggested that tobacco use,35 alcohol
consumption,35,36 dental fluorosis,34 consumption of hot
beverages,36 and exposure to biomass smoke37,38 are risk
factors. Case-control studies have been completed or are
ongoing in several countries in this region, including
Kenya, South Africa, Malawi, Uganda, Tanzania, and
Zambia, and further results are expected to be published
within the next few years.
Although GBD estimates show major variations in age-
standardised incidence, mortality, and DALYs across
regions and countries, there might be finer variations
within countries not captured by these data. A prominent
epidemiological feature of oesophageal squamous cell
carcinoma, which constitutes the majority of oesophageal
cancer cases worldwide, is that, for unknown reasons,
rates of this disease can change sharply over relatively
short distances. Therefore, countries marked as medium
risk or low risk might have areas with a very high risk of
oesophageal squamous cell carcinoma. For example,
although Iran is not marked as a high-risk country for
oesophageal cancer, Golestan Province in the northern
part of Iran, bordering Turkmenistan, has some of the
highest rates of oesophageal squamous cell carcinoma in
the world.21,39 Likewise, although India and Brazil are not
considered to be high-risk countries, certain areas of these
countries (eg, the Kashmir Valley in India and Rio Grande
do Sul in Brazil) have high rates of oesophageal cancer.20,40,41
Such stark dierences in incidence over short distances
could lead to erroneous results when spatiotemporal
smoothing methods are used. A country with no data and
low incidence rates might be considered a high-incidence
country if it has a neighbouring country with high
incidence rates. Therefore, more granular geographical
data need to be collected.3
Although there was a global decrease in age-standardised
incidence rates of oesophageal cancer between 1990
and 2017, the age-standardised rates increased in several
countries, particularly in high-income countries. This is
likely to be because the rates of oesophageal adeno-
carcinoma (but not oesophageal squamous cell carcinoma)
have increased in high-income countries (eg, the USA,
Germany, and the Netherlands) since the 1990s.5,8 The two
main histological subtypes of oesophageal cancer,
oesophageal squamous cell carcinoma and oesophageal
adenocarcinoma, have very distinct risk factors, incidence
trends, and geographical distributions.22 For example,
although alcohol consumption is a major risk factor for
oesophageal squamous cell carcinoma, it is not a risk
factor for oesophageal adenocarcinoma.42,43 Conversely,
although obesity and gastro-oesophageal reflux are major
risk factors for oesophageal adenocarcinoma,44,45 they are
not risk factors for oesophageal squamous cell carcinoma.
Thus, although we observed an overall decline in the age-
standardised rates of oesophageal cancer, the picture is
dierent for oesophageal squamous cell carcinoma and
oesophageal adenocarcinoma. The age-adjusted incidence
rates of oesophageal cancer increased in a minority
of oesophageal squamous cell carcinoma-dominant
countries, particularly in countries in sub-Saharan Africa
(eg, Chad, Benin, and Sierra Leone), which could be due to
improvements in cancer registry systems in this region.
This study found tobacco smoking, tobacco chewing,
alcohol consumption, low intake of fruit, and high BMI
to be important oesophageal cancer risk factors,
accounting for most of the burden. Of these factors, high
BMI is an established risk factor for oesophageal
adenocarcinoma but has no proven association with
oesophageal squamous cell carcinoma risk. Given the
poor survival rate of patients with oesophageal cancer,
major eorts to reduce these risk factors should be
undertaken, particularly given that many oesophageal
cancer risk factors (eg, smoking and obesity) are also
important risk factors for other major chronic diseases,
such as cardiovascular diseases and other cancers.
Although there were some exceptions, we found an
overall inverse association between the age-standardised
incidence of oesophageal cancer and SDI at the country
level. These findings are consistent with previous
epidemiological studies that have shown an inverse
association between oesophageal squamous cell
carcinoma and socioeconomic status.22,27,30,46,47 Despite
recent rises in the age-standardised incidence rates of
oesophageal adenocarcinoma, oesophageal squamous
cell carcinoma still constitutes the majority of global
oesophageal cancer cases. Therefore, on a global basis,
an inverse association between oesophageal cancer and
SDI is expected. It has been argued that substantial
decreases in the rate of oesophageal squamous cell
carcinoma in some of parts of the world might be due to
improved socioeconomic status.48 Low SDI is a proxy for
multiple correlated and interconnected variables such as
unimproved water sources and high indoor air pollution.
Indeed, recent studies have suggested that exposure to
biomass smoke and indoor air pollution, lack of access to
piped water, poor oral health, opium consum ption, and
consumption of very hot drinks are risk factors for
oesophageal squamous cell carcinoma.27,32,36
The poor prognosis of oesophageal cancer, indicated by
the high MIR, might also call for screening eorts in the
general population or in high-risk groups. Early detection
of oesophageal cancer is also appealing because
premalignant lesions and early cancers can now be
treated with methods that are less invasive than surgery,
such as endoscopic mucosal resection and endoscopic
submucosal dissection, photodynamic therapy, argon
plasma coagulation, radiofrequency ablation, and
cryotherapy.49,50 In some areas of China that have high
incidence rates of oesophageal squamous cell carcinoma
Articles
www.thelancet.com/gastrohep Published online April 1, 2020 https://doi.org/10.1016/S2468-1253(20)30007-8
11
and its precursor lesions (ie, squamous dysplasia), mass
upper gastrointestinal endoscopy has been shown to
increase survival51 and to be highly cost-eective.52
However, in most other parts of the world, the prevalence
rates of these precursor lesions are too low, even among
cigarette smokers and alcohol drinkers, to merit upper
gastrointestinal endoscopy and potentially invasive
treatment. Other screening methods, such as cytological
detection of dysplasia by use of balloon samplers, have
shown low sensitivity and specificity for precursor lesions
of oesophageal squamous cell carcinoma,53 resulting in
high false positive and false negative rates. Due to its low
prevalence and low progression rates, screening for
oesophageal adenocarcinoma via its precursor lesion
(Barrett’s oesophagus) is not cost-eective.54 Early
detection of oesophageal cancer might also occur as a
byproduct of screening for gastric cancer. For example, in
South Korea, mass screening for gastric cancer by use of
upper endoscopy or upper gastrointestinal series, which
is done as part of a national screening programme,55
might also help in early detection of oesophageal cancer.
In some parts of the world, such as in China, incidence
rates of both oesophageal cancer and gastric cancer are
high, and mass endoscopic screening eorts might be
beneficial to detect both cancers at early stages.56
Primary prevention of oesophageal cancer with
chemopreventive measures has been the subject of many
observational studies and randomised trials.57,58 Long-
term use of aspirin and other non-steroidal anti-
inflammatory drugs, statins, and anti-reflux therapy have
been suggested to reduce the risk of oesophageal
adenocarcinoma,57 whereas supplemental selenium and
other micronutrients might reduce the risk of
oesophageal squamous cell carcinoma.58,59 However, the
level of evidence is not high enough to suggest
widespread use of any of these drugs for primary
prevention of oesophageal squamous cell carcinoma or
oesophageal adenocarcinoma.59 The use of statins,
however, has been growing over the past few decades,
primarily because of their cardioprotective eects.
Presenting data from 195 countries and territories over
three decades, this study is, to our knowledge, the most
comprehensive and up-to-date analysis of the global
burden, trends, and risk factors of oesophageal cancer.
Linking data to Cancer Incidence in Five Continents
provided, we believe for the first time, an opportunity to
investigate associations with several potential risk
factors of oesophageal squamous cell carcinoma at the
country level. The data and findings, however, have
several limitations. The two main histological subtypes
of oesophageal cancer, oesophageal squamous cell
carcinoma and oesophageal adenocarcinoma, have
distinct risk factors, incidence trends, and geographical
distributions,22 but data for these two subtypes are not
currently captured independently in GBD. We suggest
collection of data by histological subtype, where possible.
By linking the GBD estimates to Cancer Incidence in
Five Continents, we were able to find a partial solution to
this limitation. As with other GBD cancer data, some
countries did not have complete mortality or incidence
data, and hence estimates were obtained by use of
modelling. This modelling could be more problematic
for oesophageal cancer than for other cancers, as rates of
oesophageal squamous cell carcin oma might be
drastically dierent across relatively short geographical
distances. There is growing evidence that consumption
of very hot drinks is a risk factor for oesophageal
squamous cell carcinoma, particularly in very high-risk
areas of the world, but GBD did not have data on this
variable.
In conclusion, despite reductions in age-standardised
incidence and mortality rates, oesophageal cancer
remains a major cause of cancer mortality and burden
across the world. The bulk of the burden of oesophageal
cancer comes from east Asia, particularly from China.
Areas with the highest age-standardised incidence,
mortality, and DALY rates are located in east and central
Asia and eastern, central, and southern sub-Saharan
Africa. Although the exact reasons for these high rates
are unclear, many epidemiological studies are ongoing,
and we expect to see new findings over the next few
years. In the meantime, intensive reduction of major
known and potential oesophageal squamous cell
carcinoma risk factors (primarily tobacco use, alcohol
consumption, indoor air pollution, and consumption of
very hot drinks) and oesophageal adenocarcinoma
(primarily obesity and tobacco use) are strongly
recommended. Where possible, it would be useful to
collect country-level data on other risk factors such as
consumption of opium and hot drinks, and water pipes
(eg, hookahs). It would also be advisable to collect data
on the histology of oesophageal cancer, and to treat
oesophageal squamous cell carcinoma and oesophageal
adeno carcinoma as two distinct entities for future
analyses. High mortality-to-incidence ratios highlight
the importance of primary and secondary prevention.
Screening might be advised only in certain geographical
areas with a very high risk of oesophageal squamous cell
carcinoma and high prevalence of squamous dysplasia.
Further development of less invasive screening methods
should be highly encouraged.
GBD 2017 Oesophageal Cancer Collaborators
Farin Kamangar, Dariush Nasrollahzadeh, Saeid Safiri,
Sadaf G Sepanlou, Christina Fitzmaurice, Kevin S Ikuta,
Catherine Bisignano, Farhad Islami, Gholamreza Roshandel,
Stephen S Lim, Hassan Abolhassani, Eman Abu-Gharbieh,
Rufus Adesoji Adedoyin, Shailesh M Advani, Muktar Beshir Ahmed,
Miloud Taki Eddine Aichour, Tomi Akinyemiju,
Chisom Joyqueenet Akunna, Fares Alahdab, Vahid Alipour,
Amir Almasi-Hashiani, Abdulaziz M Almulhim, Nahla Hamed Anber,
Alireza Ansari-Moghaddam, Jalal Arabloo, Morteza Arab-Zozani,
Atalel Fentahun Awedew, Alaa Badawi, Kathleen S Sachiko Berfield,
Kidanemaryam Berhe, Krittika Bhattacharyya, Antonio Biondi,
Tone Bjørge, Antonio Maria Borzì, Cristina Bosetti, Giulia Carreras,
Felix Carvalho, Clara Castro, Dinh-Toi Chu, Vera Marisa Costa,
Baye Dagnew, Jiregna Darega Gela, Ahmad Daryani,
Feleke Mekonnen Demeke, Gebre Teklemariam Demoz,
Articles
12
www.thelancet.com/gastrohep Published online April 1, 2020 https://doi.org/10.1016/S2468-1253(20)30007-8
Mostafa Dianatinasab, Iat Elbarazi, Mohammad Hassan Emamian,
Arash Etemadi, Pawan Sirwan Faris, Eduarda Fernandes, Irina Filip,
Florian Fischer, Mohamed M Gad, Silvano Gallus, Abadi Kahsu Gebre,
Tsegaye Tewelde Gebrehiwot, Gebreamlak Gebremedhn Gebremeskel,
Begashaw Melaku Gebresillassie, Fatemeh Ghasemi-kebria,
Ahmad Ghashghaee, Nermin Ghith, Mahaveer Golechha,
Giuseppe Gorini, Rahul Gupta, Nima Hafezi-Nejad, Arvin Haj-Mirzaian,
James D Harvey, Maryam Hashemian, Hamid Yimam Hassen,
Simon I Hay, Andualem Henok, Chi Linh Hoang, H Dean Hosgood,
Mowafa Househ, Olayinka Stephen Ilesanmi, Milena D Ilic,
Seyed Sina Naghibi Irvani, Charvi Jain, Spencer L James, Sun Ha Jee,
Ravi Prakash Jha, Farahnaz Joukar, Ali Kabir, Amir Kasaeian,
Mesfin Wudu Kassaw, Supreet Kaur, Andre Pascal Kengne,
Esma Kerboua, Yousef Saleh Khader, Rovshan Khalilov,
Ejaz Ahmad Khan, Abdullah T Khoja, Jonathan M Kocarnik,
Hamidreza Komaki, Vivek Kumar, Carlo La Vecchia, Savita Lasrado,
Bingyu Li, Alan D Lopez, Azeem Majeed, Navid Manafi,
Ana Laura Manda, Fariborz Mansour-Ghanaei, Manu Raj Mathur,
Varshil Mehta, Dhruv Mehta, Walter Mendoza, Prasanna Mithra,
Karzan Abdulmuhsin Mohammad, Abdollah Mohammadian-Hafshejani,
Reza Mohammadpourhodki, Jemal Abdu Mohammed, Farnam Mohebi,
Ali H Mokdad, Lorenzo Monasta, Delaram Moosavi,
Mahmood Moosazadeh, Ghobad Moradi, Farhad Moradpour,
Rahmatollah Moradzadeh, Gurudatta Naik, Ionut Negoi,
Haruna Asura Nggada, Huong Lan Thi Nguyen, Rajan Nikbakhsh,
Molly R Nixon, Andrew T Olagunju, Tinuke O Olagunju,
Jagadish Rao Padubidri, Keyvan Pakshir, Shanti Patel, Mona Pathak,
Hai Quang Pham, Akram Pourshams, Navid Rabiee,
Mohammad Rabiee, Amir Radfar, Alireza Rafiei, Kiana Ramezanzadeh,
Goura Kishor Rath, Priya Rathi, Salman Rawaf, David Laith Rawaf,
Nima Rezaei, Elias Merdassa Roro, Anas M Saad, Hamideh Salimzadeh,
Abdallah M Samy, Benn Sartorius, Arash Sarveazad, Mario Sekerija,
Feng Sha, Morteza Shamsizadeh, Sara Sheikhbahaei, Reza Shirkoohi,
Sudeep K Siddappa Malleshappa, Jasvinder A Singh,
Dhirendra Narain Sinha, Catalin-Gabriel Smarandache,
Sergey Soshnikov, Hafiz Ansar Rasul Suleria, Degena Bahrey Tadesse,
Berhe Etsay Tesfay, Bhaskar Thakur, Eugenio Traini, Khanh Bao Tran,
Bach Xuan Tran, Irfan Ullah, Marco Vacante, Yousef Veisani,
Isidora S Vujcic, Girmay Teklay Weldesamuel, Rixing Xu,
Vahid Yazdi-Feyzabadi, Deniz Yuce, Vesna Zadnik, Zoubida Zaidi,
Zhi-Jiang Zhang, Reza Malekzadeh, and Mohsen Naghavi.
Affiliations
Biology Department (Prof F Kamangar MD), Morgan State University,
Baltimore, MD, USA; Cancer Biology Research Center
(R Shirkoohi PhD), Cancer Research Institute (R Shirkoohi PhD),
Department of Pharmacology (A Haj-Mirzaian MD), Digestive Diseases
Research Center (Prof R Malekzadeh MD), Digestive Diseases Research
Institute (S G Sepanlou MD, G Roshandel PhD, M Hashemian PhD,
Prof A Pourshams MD, H Salimzadeh PhD), Digestive Oncology
Research Center (Prof F Kamangar MD), Endocrinology and Metabolism
Research Center (S Sheikhbahaei MD), Hematology, Oncology and Stem
Cell Transplantation Research Center (A Kasaeian PhD), National
Institute of Health Research (NIHR) (F Mohebi MD),
Non-communicable Diseases Research Center (F Mohebi MD),
Research Center for Immunodeficiencies (H Abolhassani PhD,
Prof N Rezaei PhD), School of Medicine (N Hafezi-Nejad MD), Tehran
University of Medical Sciences, Tehran, Iran (A Etemadi PhD); Genetic
Epidemiology Group (D Nasrollahzadeh PhD), International Agency for
Research on Cancer, Lyon, France; Aging Research Institute
(S Safiri PhD), Department of Community Medicine (S Safiri PhD),
Tabriz University of Medical Sciences, Tabriz, Iran; Department of
Epidemiology (M Dianatinasab MSc), Non-communicable Disease
Research Center (S G Sepanlou MD, Prof R Malekzadeh MD),
Department of Parasitology and Mycology (Prof K Pakshir PhD), Shiraz
University of Medical Sciences, Shiraz, Iran; Department of Health
Metrics Sciences, School of Medicine (C Fitzmaurice MD,
Prof S S Lim PhD, Prof S I Hay FMedSci, Prof A D Lopez PhD,
Prof A H Mokdad PhD, Prof B Sartorius PhD, Prof M Naghavi MD),
Department of Surgery (K S S Berfield MD), Division of Allergy and
Infectious Diseases (K S Ikuta MD), Institute for Health Metrics and
Evaluation (C Fitzmaurice MD, K S Ikuta MD, C Bisignano MPH,
Prof S S Lim PhD, J D Harvey BS, Prof S I Hay FMedSci, S L James MD,
J M Kocarnik PhD, Prof A D Lopez PhD, Prof A H Mokdad PhD,
M R Nixon PhD, R Xu BS, Prof M Naghavi MD), University of
Washington, Seattle, WA, USA; Surveillance and Health Services
Research (F Islami MD), American Cancer Society, Atlanta, GA, USA;
Golestan Research Center of Gastroenterology and Hepatology
(G Roshandel PhD, F Ghasemi-kebria MSc), Golestan University of
Medical Sciences, Gorgan, Iran; Department of Laboratory Medicine
(H Abolhassani PhD), Karolinska University Hospital, Huddinge,
Sweden; College of Medicine (E Abu-Gharbieh PhD), University of
Sharjah, Sharjah, United Arab Emirates; Department of Medical
Rehabilitation (Prof R A Adedoyin PhD), Obafemi Awolowo University,
Ile-Ife, Nigeria; Social and Behavioral Research Branch
(S M Advani PhD), National Institute of Health, Bethesda, MD, USA;
Department of Oncology (S M Advani PhD), Georgetown University,
Washington, DC, USA; Department of Epidemiology (M B Ahmed MPH,
T T Gebrehiwot MPH), Jimma University, Jimma, Ethiopia; Australian
Center for Precision Health (M B Ahmed MPH), University of South
Australia, Adelaide, Australia; Higher National School of Veterinary
Medicine, Algiers, Algeria (M Aichour MA); Department of Population
Health Sciences (T Akinyemiju PhD), Duke Global Health Institute
(T Akinyemiju PhD), Duke University, Durham, NC, USA; Department
of Public Health (C J Akunna DMD), The Intercountry Centre for Oral
Health (ICOH) for Africa, Jos, Nigeria; Department of Public Health
(C J Akunna DMD), Federal Ministry of Health, Garki, Nigeria; Mayo
Evidence-based Practice Center (F Alahdab MSc), Mayo Clinic
Foundation for Medical Education and Research, Rochester, MN, USA;
Colorectal Research Center (A Sarveazad PhD), Health Economics
Department (V Alipour PhD), Health Management and Economics
Research Center (V Alipour PhD, J Arabloo PhD, A Ghashghaee BSc),
Minimally Invasive Surgery Research Center (A Kabir MD),
Ophthalmology Department (N Manafi MD), Pars Advanced and
Minimally Invasive Medical Manners Research Center (A Kasaeian PhD),
Student Research Committee (A Ghashghaee BSc), Iran University of
Medical Sciences, Tehran, Iran (D Moosavi MD); Department of
Epidemiology (A Almasi-Hashiani PhD, R Moradzadeh PhD), Arak
University of Medical Sciences, Arak, Iran; College of Medicine
(A M Almulhim MBBS), Imam Abdulrahman Bin Faisal University,
Dammam, Saudi Arabia; Faculty of Medicine (N H Anber DrPH),
Mansoura University, Mansoura, Egypt (N H Anber DrPH); Department
of Epidemiology and Biostatistics (Prof A Ansari-Moghaddam PhD),
Health Promotion Research Center, Zahedan, Iran; Social Determinants
of Health Research Center (M Arab-Zozani PhD), Birjand University of
Medical Sciences, Iran; Department of Surgery (A F Awedew MD), Debre
Tabor University, Debre Tabor, Ethiopia; Public Health Risk Sciences
Division (A Badawi PhD), Public Health Agency of Canada, Toronto, ON,
Canada; Department of Nutritional Sciences (A Badawi PhD), University
of Toronto, Toronto, ON, Canada; Department of Veterans Aairs,
Seattle, WA, USA (K S S Berfield MD); USA, (K S S Berfield MD);
Department of Nursing (G G Gebremeskel MSc), Department of
Nutrition and Dietetics (K Berhe MPH), School of Pharmacy
(A K Gebre MSc), Mekelle University, Mekelle, Ethiopia; Department of
Statistical and Computational Genomics (K Bhattacharyya MSc), National
Institute of Biomedical Genomics, Kalyani, India; Department of
Statistics (K Bhattacharyya MSc), University of Calcutta, Kolkata, India;
Department of Clinical and Experimental Medicine (A M Borzì MD),
Department of General Surgery and Medical-Surgical Specialties
(Prof A Biondi PhD, M Vacante PhD), University of Catania, Catania,
Italy; Department of Global Public Health and Primary Care
(Prof T Bjørge PhD), University of Bergen, Bergen, Norway; Cancer
Registry of Norway, Oslo, Norway (Prof T Bjørge PhD); Department of
Environmental Health Sciences (S Gallus DSc), Department of Oncology
(C Bosetti PhD), Mario Negri Institute for Pharmacological Research,
Milan, Italy; Oncologic Network, Prevention and Research Institute
(ISPRO) (G Gorini MD), Institute for Cancer Research, Prevention and
Clinical Network, Florence, Italy (G Carreras PhD); Institute of Public
Health (Prof C Castro PhD), LAQV/REQUIMTE (Prof E Fernandes PhD),
Research Unit on Applied Molecular Biosciences (UCIBIO)
(Prof F Carvalho PhD, V M Costa PhD), University of Porto, Porto,
Portugal; Department of Epidemiology (Prof C Castro PhD), Portuguese
Oncology Institute of Porto, Porto, Portugal; Faculty of Biology
Articles
www.thelancet.com/gastrohep Published online April 1, 2020 https://doi.org/10.1016/S2468-1253(20)30007-8
13
(D Chu PhD), Hanoi National University of Education, Hanoi, Vietnam;
Clinical Pharmacy (B Gebresillassie MSc), Department of Human
Physiology (B Dagnew MSc), University of Gondar, Gondar, Ethiopia;
Department of Public Health (J Darega Gela MPH), Ambo University,
Ambo, Ethiopia; Department of Immunology (Prof A Rafiei PhD), Health
Sciences Research Center (M Moosazadeh PhD), Molecular and Cell
Biology Research Center (Prof A Rafiei PhD), Toxoplasmosis Research
Center (Prof A Daryani PhD), Mazandaran University of Medical
Sciences, Sari, Iran; Department of Medical Laboratory Sciences
(F M Demeke MSc), Bahir Dar University, Bahir Dar, Ethiopia;
Department of Nursing (G G Gebremeskel MSc, D B Tadesse MSc,
G T Weldesamuel MSc), School of Pharmacy (G T Demoz MSc), Aksum
University, Aksum, Ethiopia; School of Public Health (E M Roro MPH),
Addis Ababa University, Addis Ababa, Ethiopia (G T Demoz MSc);
Department of Epidemiology and Biostatistics (M Dianatinasab MSc),
Ophthalmic Epidemiology Research Center (M Emamian PhD),
Shahroud University of Medical Sciences, Shahroud, Iran; College of
Health Sciences (I Elbarazi DrPH), Abu Dhabi University, Abu Dhabi,
United Arab Emirates; Division of Cancer Epidemiology and Genetics
(A Etemadi PhD), National Cancer Institute, Bethesda, MD, USA;
Department of Biology and Biotechnology “L. Spallanzani”
(P S Faris PhD), University of Pavia, Pavia, Italy; Department of Biology
(P S Faris PhD, K A Mohammad PhD), Salahaddin University-Erbil,
Erbil, Iraq; Psychiatry Department (I Filip MD), Kaiser Permanente,
Fontana, CA, USA; College of Graduate Health Sciences (A Radfar MD),
School of Health Sciences (I Filip MD), A.T. Still University, Mesa, AZ,
USA; Institute of Gerontological Health Services and Nursing Research
(F Fischer PhD), Ravensburg-Weingarten University of Applied Sciences,
Weingarten, Germany; Department of Cardiovascular Medicine
(M M Gad MD), Heart and Vascular Institute (A M Saad MD), Cleveland
Clinic, Cleveland, OH, USA; Gillings School of Global Public Health
(M M Gad MD), University of North Carolina Chapel Hill, Chapel Hill,
NC, USA; School of Medical and Health Sciences (A K Gebre MSc), Edith
Cowan University, Perth, Australia; School of Medicine and Public Health
(B Gebresillassie MSc), Newcastle University, Newcastle, Australia;
Research Group for Genomic Epidemiology (N Ghith PhD), Technical
University of Denmark, Copenhagen, Denmark; Research Unit of Social
Epidemiology (N Ghith PhD), Lund University, Malmö, Sweden; Health
Systems and Policy Research (M Golechha PhD), Indian Institute of
Public Health Gandhinagar, Gandhinagar, India; March of Dimes,
Arlington, VA, USA (Prof R Gupta MD); Health Policy, Management and
Leadership (Prof R Gupta MD), West Virginia University School of Public
Health, Morgantown, WV, USA; Department of Health Policy and
Management (A T Khoja MD), Department of Radiology
(S Sheikhbahaei MD), Department of Radiology and Radiological
Sciences (N Hafezi-Nejad MD), Johns Hopkins University, Baltimore,
MD, USA; Department of Pharmacology (R Nikbakhsh MD), Obesity
Research Center (A Haj-Mirzaian MD), Research Institute for Endocrine
Sciences (S N Irvani MD), School of Pharmacy
(K Ramezanzadeh PharmD), Shahid Beheshti University of Medical
Sciences, Tehran, Iran; Biology Department (M Hashemian PhD), Utica
College, Utica, NY, USA; Primary and Interdisciplinary care
(H Y Hassen MPH), University Hospital Antwerp, Antwerp, Belgium;
Department of Public Health (H Y Hassen MPH, A Henok MPH),
Mizan-Tepi University, Mizan Teferi, Ethiopia; Center of Excellence in
Behavioral Medicine (C L Hoang BMedSci), Nguyen Tat Thanh
University, Ho Chi Minh City, Vietnam; Epidemiology and Population
Health (H Hosgood PhD), Albert Einstein College of Medicine, Bronx,
NY, USA; Division of Information and Computing Technology
(Prof M Househ PhD), Hamad Bin Khalifa University, Doha, Qatar;
Department of Community Medicine (O S Ilesanmi PhD), University of
Ibadan, Ibadan, Nigeria; Department of Community Medicine
(O S Ilesanmi PhD), University College Hospital Ibadan, Ibadan, Nigeria;
Department of Epidemiology (Prof M D Ilic PhD), University of
Kragujevac, Kragujevac, Serbia; School of Medical Sciences (C Jain MD),
Kathmandu University, Chitwan, Nepal; Department of Epidemiology
and Health Promotion (Prof S Jee PhD), Yonsei University, Seoul, South
Korea; Harvard Medical School (Prof S Jee PhD), Harvard University,
Boston, MA, USA; Department of Community Medicine (R P Jha MSc),
Dr Baba Saheb Ambedkar Medical College & Hospital, Delhi, India;
Department of Community Medicine (R P Jha MSc), Banaras Hindu
University, Varanasi, India; Caspian Digestive Disease Research Center
(F Joukar PhD, Prof F Mansour-Ghanaei MD), Gastrointestinal and Liver
Diseases Research Center (F Joukar PhD, Prof F Mansour-Ghanaei MD),
Guilan University of Medical Sciences, Rasht, Iran; Department of
Nursing (M W Kassaw MSc), Woldia University, Woldia, Ethiopia;
Amhara Public Health Institute, Bair Dar, Ethiopia (M W Kassaw MSc);
Hematology/Oncology (S Kaur MD), St Joseph University Medical
Center, Paterson, NJ, USA; Non-communicable Diseases Research Unit
(Prof A P Kengne PhD), Medical Research Council South Africa, Cape
Town, South Africa; Department of Medicine (Prof A P Kengne PhD),
University of Cape Town, Cape Town, South Africa; Department of
Medical Oncology (Prof E Kerboua DSc), Pierre & Marie Curie Center,
Algiers, Algeria; Department of Public Health (Prof Y S Khader PhD),
Jordan University of Science and Technology, Irbid, Jordan; Biophysics
and Molecular Biology (Prof R Khalilov PhD), Baku State University,
Baku, Azerbaijan; Institute of Radiation Problems (Prof R Khalilov PhD),
Azerbaijan National Academy of Sciences, Baku, Azerbaijan; Department
of Epidemiology and Biostatistics (E A Khan MPH), Health Services
Academy, Islamabad, Pakistan; Department of Public Health
(A T Khoja MD), Imam Mohammad Ibn Saud Islamic University,
Riyadh, Saudi Arabia; Public Health Sciences Division
(J M Kocarnik PhD), Fred Hutchinson Cancer Research Center, Seattle,
WA, USA; Neurophysiology Research Center (H Komaki MD), Hamadan
University of Medical Sciences, Hamadan, Iran; Brain Engineering
Research Center (H Komaki MD), Institute for Research in Fundamental
Sciences, Tehran, Iran; Department of Medicine (V Kumar MD),
Brigham and Women’s Hospital, Boston, MA, USA; Clinical Medicine
and Community Health (Prof C La Vecchia MD), University of Milan,
Milano, Italy; Department of Otorhinolaryngology (S Lasrado MS), Father
Muller Medical College, Mangalore, India; Department of Sociology
(B Li PhD), Shenzhen University, Shenzhen, China; Department of
Agriculture and Food Systems (H Suleria PhD), Melbourne School of
Population and Global Health (Prof A D Lopez PhD), University of
Melbourne, Melbourne, VIC, Australia; Department of Primary Care and
Public Health (Prof A Majeed MD), Primary Care and Public Health
(Prof S Rawaf MD), WHO Collaborating Centre for Public Health
Education and Training (D L Rawaf MD), Imperial College London,
London, UK; Ophthalmology Department (N Manafi MD), University of
Manitoba, Winnipeg, MB, Canada; General Surgery Department I
(A Manda MD), Emergency University Hospital Bucharest, Bucharest,
Romania; General Surgery Department (A Manda MD, I Negoi PhD,
C Smarandache MD), Carol Davila University of Medicine and Pharmacy,
Bucharest, Romania; Health Policy Research (M R Mathur PhD), Public
Health Foundation of India, Gurugram, India; Institute of Population
Health Sciences (M R Mathur PhD), University of Liverpool, Liverpool,
UK; Cardiology Department (V Mehta MD), West Middlesex University
Hospital, London, UK; Division of Gastroenterology and Hepatobiliary
Disease (D Mehta MD), New York Medical College, Valhalla, NY, USA;
Peru Country Oce (W Mendoza MD), United Nations Population Fund
(UNFPA), Lima, Peru; Department of Community Medicine
(P Mithra MD), Department of Forensic Medicine (J Padubidri MD),
Kasturba Medical College (P Rathi MD), Manipal Academy of Higher
Education, Mangalore, India; Tishk International University, Erbil, Iraq
(K A Mohammad PhD); Department of Epidemiology and Biostatistics
(A Mohammadian-Hafshejani PhD), Shahrekord University of Medical
Sciences, Shahrekord, Iran; Kashmar Center of Higher Health Education
(R Mohammadpourhodki MSc), Mashhad University of Medical
Sciences, Mashhad, Iran; Department of Public Health
(J A Mohammed MPH), Samara University, Samara, Ethiopia; Clinical
Epidemiology and Public Health Research Unit (L Monasta DSc), Burlo
Garofolo Institute for Maternal and Child Health, Trieste, Italy;
Department of Epidemiology and Biostatistics (G Moradi PhD), Social
Determinants of Health Research Center (G Moradi PhD,
F Moradpour PhD), Kurdistan University of Medical Sciences, Sanandaj,
Iran; Comprehensive Cancer Center (G Naik MPH), Department of
Medicine (Prof J A Singh MD), University of Alabama at Birmingham,
Birmingham, AL, USA; General Surgery Department (I Negoi PhD,
C Smarandache MD), Emergency Hospital of Bucharest, Bucharest,
Romania; Department of Histopathology (Prof H A Nggada MD),
University of Maiduguri Teaching Hospital, Maiduguri, Nigeria;
Department of Human Pathology (Prof H A Nggada MD), University of
Articles
14
www.thelancet.com/gastrohep Published online April 1, 2020 https://doi.org/10.1016/S2468-1253(20)30007-8
Maiduguri, Maiduguri, Nigeria; Institute for Global Health Innovations
(H L T Nguyen MPH, H Q Pham MD), Duy Tan University, Hanoi,
Vietnam; Heidelberg University Hospital, Germany (R Nikbakhsh MD);
Department of Pathology and Molecular Medicine (T O Olagunju MD),
Department of Psychiatry and Behavioural Neurosciences
(A T Olagunju MD), McMaster University, Hamilton, ON, Canada;
Department of Psychiatry (A T Olagunju MD), University of Lagos,
Lagos, Nigeria; Department of Medicine (S Patel MD), Yale University,
New Haven, NY, USA; Research & Development Department
(M Pathak PhD), Kalinga Institute of Medical Sciences, Bhubaneswar,
India; Department of Chemistry (N Rabiee MSc), Sharif University of
Technology, Tehran, Iran; Biomedical Engineering Department
(Prof M Rabiee PhD), Amirkabir University of Technology, Tehran, Iran;
College of Medicine (A Radfar MD), University of Central Florida,
Orlando, FL, USA; Department of Radiation Oncology
(Prof G K Rath MD), All India Institute of Medical Sciences, New Delhi,
India; Academic Public Health Support (Prof S Rawaf MD), Public
Health England, London, UK; University College London Hospitals,
London, UK (D L Rawaf MD); Network of Immunity in Infection,
Malignancy and Autoimmunity (NIIMA) (Prof N Rezaei PhD), Universal
Scientific Education and Research Network (USERN), Tehran, Iran;
Public Health Department (E M Roro MPH), Wollega University,
Nekemte, Ethiopia; Department of Entomology (A M Samy PhD),
Ain Shams University, Cairo, Egypt; Faculty of Infectious and Tropical
Diseases (Prof B Sartorius PhD), London School of Hygiene & Tropical
Medicine, London, UK; Department of Medical Statistics, Epidemiology,
and Medical Informatics (M Sekerija PhD), University of Zagreb, Zagreb,
Croatia; Division of Epidemiology and Prevention of Chronic Non-
communicable Diseases (M Sekerija PhD), Croatian Institute of Public
Health, Zagreb, Croatia; Center for Biomedical Information Technology
(F Sha PhD), Shenzhen Institutes of Advanced Technology, Shenzhen,
China; Faculty of Caring Science, Work Life and Social Welfare
(M Shamsizadeh MSc), University of Borås, Borås, Sweden; Department
of Hematology-Oncology (S K Siddappa Malleshappa MD), Baystate
Medical Center, Springfield, MA, USA; Medical Service Rheumatology
(Prof J A Singh MD), US Department of Veterans Aairs, Birmingham,
AL, USA; Department of Epidemiology (D N Sinha PhD), School of
Preventive Oncology, Patna, India; Department of Epidemiology
(D N Sinha PhD), Healis Sekhsaria Institute for Public Health, Mumbai,
India; Department of Research Development (S Soshnikov PhD), Federal
Research Institute for Health Organization and Informatics of the
Ministry of Health (FRIHOI), Moscow, Russia; Laboratory of Public
Health Indicators Analysis and Health Digitalization (S Soshnikov PhD),
Moscow Institute of Physics and Technology, Moscow, Russia; Axum
College of Health Science, Mekelle, Ethiopia (D B Tadesse MSc);
Department of Public Health (B E Tesfay MPH), Adigrat University,
Adigrat, Ethiopia; Division of Biostatistics and Epidemiology
(B Thakur PhD), Texas Tech University, El Paso, TX, USA; Institute for
Risk Assessment Sciences (IRAS) (E Traini MSc), Utrecht University,
Utrecht, Netherlands; Department of Molecular Medicine and Pathology
(K B Tran MD), University of Auckland, Auckland, New Zealand;
Department of Health Economics (B X Tran PhD), Hanoi Medical
University, Hanoi, Vietnam; Department of Microbiology (I Ullah PhD),
Iqra National University, Peshawar, Pakistan; TB Culture Laboratory
(I Ullah PhD), Mufti Mehmood Memorial Teaching Hospital, Dera Ismail
Khan, Pakistan; Psychosocial Injuries Research Center (Y Veisani PhD),
Ilam University of Medical Sciences, Ilam, Iran; Faculty of Medicine
Institute of Epidemiology (I S Vujcic PhD), University of Belgrade,
Belgrade, Serbia; Department of Health Management, Policy, and
Economics (V Yazdi-Feyzabadi PhD), Health Services Management
Research Center (V Yazdi-Feyzabadi PhD), Kerman University of Medical
Sciences, Kerman, Iran; Department of Preventive Oncology
(D Yuce MD), Hacettepe University, Ankara, Turkey; Epidemiology and
Cancer Registry Sector (Prof V Zadnik PhD), Institute of Oncology
Ljubljana, Ljubljana, Slovenia; Department of Medicine
(Prof Z Zaidi PhD), University Ferhat Abbas of Setif, Setif, Algeria; and
School of Medicine (Z Zhang PhD), Wuhan University, Wuhan, China.
Contributors
F Kamangar, D Nasrollahzadeh, S Safiri, S G Sepanlou, and
G Roshandel prepared the first draft. R Malekzadeh, F Kamangar,
F Islami, C Fitzmaurice, J M Kocarnik, T Akinyemiju, and C J Akunna
provided overall guidance. R Malekzadeh, F Kamangar,
D Nasrollahzadeh, F Islami, C Fitzmaurice, and T Akinyemiju
managed the project. F Kamangar, D Nasrollahzadeh, S Safiri,
S G Sepanlou, J D Harvey, A Pourshams, R Xu, J M Kocarnik, and
C J Akunna analysed the data. R Malekzadeh, F Kamangar, F Islami,
and D Nasrollahzadeh finalised the manuscript on the basis of
comments from other authors and reviewer feedback. All other authors
provided data, developed models, reviewed results, provided guidance
on methods, and reviewed and contributed to the manuscript.
Declaration of interests
S L James reports grants from Sanofi Pasteur, and, as of March 16, 2020,
employment with Genentech, outside the submitted work. J A Singh
reports personal fees from Crealta/Horizon, Medisys, Fidia, UBM LLC,
Trio health, Medscape, WebMD, Clinical Care options, Clearview
Healthcare Partners, Putnam associates, Spherix, Practice Point
communications, the National Institutes of Health and the American
College of Rheumatology, and from Simply Speaking, owning stock
options in Amarin pharmaceuticals and Viking pharmaceuticals,
non-financial support from the US Food and Drug Administration
(FDA) Arthritis Advisory Committee, Veterans Aairs Rheumatology
Field Advisory Committee, UAB Cochrane Musculoskeletal Group
Satellite Center on Network Meta-analysis, and from the Steering
committee of OMERACT, an international organization that develops
measures for clinical trials and receives arm’s length funding from
12 pharmaceutical companies, all outside the submitted work. All other
authors declare no competing interests.
Acknowledgments
A Badawi acknowledges support from the Public Health Agency of
Canada. F Carvalho acknowledges UCIBIO support, financed by
national funds from FCT/MCTES (UIDB/04378/2020). E Fernandes
acknowledges LAQV/REQUIMTE support, financed by national funds
from FCT/MCTES (UIDB/50006/2020) V M Costa acknowledges her
grant (SFRH/BHD/110001/2015), received by Portuguese national funds
through Fundaco para a Ciencia e Tecnologia (FCT), IP, under the
Norma Transitaria DL57/2016/CP1334/CT0006. A P Kengne
acknowledges support from the South African Medical Research
Council. P Rathi acknowledges support from the Manipal Academy of
Higher Education. A M Samy acknowledges receiving a fellowship from
the Egyptian Fulbright Mission Program. S Soshnikov oers thanks to
the Moscow Institute of Physics and Technology (State University),
Dolgoprudny, Moscow Region.
References
1 Global Burden of Disease Cancer Collaboration. Global, regional,
and national cancer incidence, mortality, years of life lost, years
lived with disability, and disability-adjusted life-years for 32 cancer
groups, 1990 to 2015: a systematic analysis for the Global Burden of
Disease Study. JAMA Oncol 2017; 3: 524–48.
2 Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A.
Global cancer statistics 2018: GLOBOCAN estimates of incidence
and mortality worldwide for 36 cancers in 185 countries.
CA Cancer J Clin 2018; 68: 394–424.
3 Global Burden of Disease Cancer Collaboration. Global, regional,
and national cancer incidence, mortality, years of life lost, years
lived with disability, and disability-adjusted life-years for 29 cancer
groups, 1990 to 2017: a systematic analysis for the global burden of
disease study. JAMA Oncol 2019; 5: 1749–68.
4 Cook MB, Chow WH, Devesa SS. Oesophageal cancer incidence in
the United States by race, sex, and histologic type, 1977–2005.
Br J Cancer 2009; 101: 855–59.
5 Devesa SS, Blot WJ, Fraumeni JF Jr. Changing patterns in the
incidence of esophageal and gastric carcinoma in the United States.
Cancer 1998; 83: 2049–53.
6 Gupta B, Kumar N. Worldwide incidence, mortality and time trends
for cancer of the oesophagus. Eur J Cancer Prev 2017; 26: 107–18.
7 Arnold M, Soerjomataram I, Ferlay J, Forman D. Global incidence
of oesophageal cancer by histological subtype in 2012. Gut 2015;
64: 381–87.
8 Arnold M, Laversanne M, Brown LM, Devesa SS, Bray F. Predicting
the future burden of esophageal cancer by histological subtype:
international trends in incidence up to 2030. Am J Gastroenterol
2017; 112: 1247–55.
Articles
www.thelancet.com/gastrohep Published online April 1, 2020 https://doi.org/10.1016/S2468-1253(20)30007-8
15
9 Roth GA, Abate D, Abate KH, et al. Global, regional, and national
age-sex-specific mortality for 282 causes of death in 195 countries
and territories, 1980–2017: a systematic analysis for the Global
Burden of Disease Study 2017. Lancet 2018; 392: 1736–88.
10 James SL, Abate D, Abate KH, et al. Global, regional, and national
incidence, prevalence, and years lived with disability for
354 diseases and injuries for 195 countries and territories, 1990–
2017: a systematic analysis for the Global Burden of Disease Study
2017. Lancet 2018; 392: 1789–858.
11 Kyu HH, Abate D, Abate KH, et al. Global, regional, and national
disability-adjusted life-years (DALYs) for 359 diseases and injuries
and healthy life expectancy (HALE) for 195 countries and territories,
1990–2017: a systematic analysis for the Global Burden of Disease
Study 2017. Lancet 2018; 392: 1859–922.
12 Stanaway JD, Afshin A, Gakidou E, et al. Global, regional, and
national comparative risk assessment of 84 behavioural,
environmental and occupational, and metabolic risks or clusters of
risks for 195 countries and territories, 1990–2017: a systematic
analysis for the Global Burden of Disease Study 2017. Lancet 2018;
392: 1923–94.
13 Murray CJL, Callender CSKH, Kuliko XR, et al. Population and
fertility by age and sex for 195 countries and territories, 1950–2017:
a systematic analysis for the Global Burden of Disease Study 2017.
Lancet 2018; 392: 1995–2051.
14 Afshin A, Sur PJ, Fay KA, et al. Health eects of dietary risks in
195 countries, 1990–2017: a systematic analysis for the Global
Burden of Disease Study 2017. Lancet 2019; 393: 1958–72.
15 Foreman KJ, Lozano R, Lopez AD, Murray CJ. Modeling causes of
death: an integrated approach using CODEm. Popul Health Metr
2012; 10: 1.
16 Neal RD, Din NU, Hamilton W, et al. Comparison of cancer
diagnostic intervals before and after implementation of NICE
guidelines: analysis of data from the UK General Practice Research
Database. Br J Cancer 2014; 110: 584–92.
17 Noone A, Howlader N, Krapcho M, et al. SEER Cancer Statistics
Review, 1975–2015. Bethesda, MD: National Cancer Institute, 2018.
18 Fullman N, Yearwood J, Abay SM, et al. Measuring performance on
the Healthcare Access and Quality Index for 195 countries and
territories and selected subnational locations: a systematic analysis
from the Global Burden of Disease Study 2016. Lancet 2018;
391: 2236–71.
19 Kmet J, Mahboubi E. Esophageal cancer in the Caspian littoral of
Iran: initial studies. Science 1972; 175: 846–53.
20 Khuroo MS, Zargar SA, Mahajan R, Banday MA. High incidence of
oesophageal and gastric cancer in Kashmir in a population with
special personal and dietary habits. Gut 1992; 33: 11–15.
21 Kamangar F, Malekzadeh R, Dawsey SM, Saidi F. Esophageal cancer
in Northeastern Iran: a review. Arch Iran Med 2007; 10: 70–82.
22 Kamangar F, Chow WH, Abnet CC, Dawsey SM. Environmental
causes of esophageal cancer. Gastroenterol Clin North Am 2009;
38: 27–57.
23 Islami F, Kamangar F, Aghcheli K, et al. Epidemiologic features of
upper gastrointestinal tract cancers in Northeastern Iran.
Br J Cancer 2004; 90: 1402–06.
24 Wang SM, Abnet CC, Qiao YL. What have we learned from Linxian
esophageal cancer etiological studies? Thorac Cancer 2019;
10: 1036–42.
25 Tran GD, Sun XD, Abnet CC, et al. Prospective study of risk factors
for esophageal and gastric cancers in the Linxian general population
trial cohort in China. Int J Cancer 2005; 113: 456–63.
26 Nasrollahzadeh D, Kamangar F, Aghcheli K, et al. Opium, tobacco,
and alcohol use in relation to oesophageal squamous cell carcinoma
in a high-risk area of Iran. Br J Cancer 2008; 98: 1857–63.
27 Sheikh M, Poustchi H, Pourshams A, et al. Individual and
combined eects of environmental risk factors for esophageal
cancer based on results from the Golestan Cohort Study.
Gastroenterology 2019; 156: 1416–27.
28 Islami F, Poustchi H, Pourshams A, et al. A prospective study of tea
drinking temperature and risk of esophageal squamous cell
carcinoma. Int J Cancer 2019.
29 Abedi-Ardekani B, Kamangar F, Hewitt SM, et al. Polycyclic
aromatic hydrocarbon exposure in oesophageal tissue and risk of
oesophageal squamous cell carcinoma in north-eastern Iran. Gut
2010; 59: 1178–83.
30 Islami F, Kamangar F, Nasrollahzadeh D, et al. Socio-economic
status and oesophageal cancer: results from a population-based case-
control study in a high-risk area. Int J Epidemiol 2009; 38: 978–88.
31 Dar NA, Islami F, Bhat GA, et al. Poor oral hygiene and risk of
esophageal squamous cell carcinoma in Kashmir. Br J Cancer 2013;
109: 1367–72.
32 Yu C, Tang H, Guo Y, et al. Hot tea consumption and its
interactions with alcohol and tobacco use on the risk for esophageal
cancer: a population-based cohort study. Ann Intern Med 2018;
168: 489–97.
33 Li HR, Liu QB, Wang WY, et al. Fluoride in drinking water, brick tea
infusion and human urine in two counties in Inner Mongolia,
China. J Hazard Mater 2009; 167: 892–95.
34 Menya D, Maina SK, Kibosia C, et al. Dental fluorosis and oral
health in the African Esophageal Cancer Corridor: Findings from
the Kenya ESCCAPE case-control study and a pan-African
perspective. Int J Cancer 2018.
35 Sewram V, Sitas F, O’Connell D, Myers J. Tobacco and alcohol as
risk factors for oesophageal cancer in a high incidence area in
South Africa. Cancer Epidemiol 2016; 41: 113–21.
36 Menya D, Kigen N, Oduor M, et al. Traditional and commercial
alcohols and esophageal cancer risk in Kenya. Int J Cancer 2019;
144: 459–69.
37 Kayamba V, Heimburger DC, Morgan DR, Atadzhanov M, Kelly P.
Exposure to biomass smoke as a risk factor for oesophageal and
gastric cancer in low-income populations: a systematic review.
Malawi Med J 2017; 29: 212–17.
38 Mlombe YB, Rosenberg NE, Wolf LL, et al. Environmental risk
factors for oesophageal cancer in Malawi: A case-control study.
Malawi Med J 2015; 27: 88–92.
39 Mahboubi E, Kmet J, Cook PJ, Day NE, Ghadirian P,
Salmasizadeh S. Oesophageal cancer studies in the Caspian
Littoral of Iran: the Caspian cancer registry. Br J Cancer 1973;
28: 197–214.
40 Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence
of 25 major cancers in 1990. Int J Cancer 1999; 80: 827–41.
41 Fagundes RB, Abnet CC, Strickland PT, et al. Higher urine
1-hydroxy pyrene glucuronide (1-OHPG) is associated with tobacco
smoke exposure and drinking maté in healthy subjects from Rio
Grande do Sul, Brazil. BMC Cancer 2006; 6: 139.
42 Freedman ND, Murray LJ, Kamangar F, et al. Alcohol intake and
risk of oesophageal adenocarcinoma: a pooled analysis from the
BEACON Consortium. Gut 2011; 60: 1029–37.
43 Lubin JH, Cook MB, Pandeya N, et al. The importance of exposure
rate on odds ratios by cigarette smoking and alcohol consumption
for esophageal adenocarcinoma and squamous cell carcinoma in
the Barrett’s Esophagus and Esophageal Adenocarcinoma
Consortium. Cancer Epidemiol 2012; 36: 306–16.
44 Hoyo C, Cook MB, Kamangar F, et al. Body mass index in relation
to oesophageal and oesophagogastric junction adenocarcinomas:
a pooled analysis from the International BEACON Consortium.
Int J Epidemiol 2012; 41: 1706–18.
45 Cook MB, Corley DA, Murray LJ, et al. Gastroesophageal reflux in
relation to adenocarcinomas of the esophagus: a pooled analysis
from the Barrett’s and Esophageal Adenocarcinoma Consortium
(BEACON). PLoS One 2014; 9: e103508.
46 Dar NA, Shah IA, Bhat GA, et al. Socioeconomic status and
esophageal squamous cell carcinoma risk in Kashmir, India.
Cancer Sci 2013; 104: 1231–36.
47 Vizcaino AP, Parkin DM, Skinner ME. Risk factors associated with
oesophageal cancer in Bulawayo, Zimbabwe. Br J Cancer 1995;
72: 769–73.
48 Khademi H, Kamangar F. Esophageal cancer incidence trends in
northeastern Iran: comparing rates over 36 years. Arch Iran Med
2012; 15: 194–95.
49 Wu H, Minamide T, Yano T. Role of photodynamic therapy in the
treatment of esophageal cancer. Dig Endosc 2019; 31: 508–16.
50 di Pietro M, Canto MI, Fitzgerald RC. Endoscopic management of
early adenocarcinoma and squamous cell carcinoma of the
esophagus: screening, diagnosis, and therapy. Gastroenterology 2018;
154: 421–36.
51 Wei W-Q, Chen Z-F, He Y-T, et al. Long-term follow-up of a
community assignment, one-time endoscopic screening study of
esophageal cancer in China. J Clin Oncol 2015; 33: 1951–57.
Articles
16
www.thelancet.com/gastrohep Published online April 1, 2020 https://doi.org/10.1016/S2468-1253(20)30007-8
52 Yang J, Wei W-Q, Niu J, Liu Z-C, Yang C-X, Qiao Y-L. Cost-benefit
analysis of esophageal cancer endoscopic screening in high-risk
areas of China. World J Gastroenterol 2012; 18: 2493–501.
53 Pan Q-J, Roth MJ, Guo H-Q, et al. Cytologic detection of esophageal
squamous cell carcinoma and its precursor lesions using balloon
samplers and liquid-based cytology in asymptomatic adults in
Llinxian, China. Acta Cytol 2008; 52: 14–23.
54 Shaheen NJ, Palmer LB. Improving screening practices for Barrett’s
esophagus. Surg Oncol Clin N Am 2009; 18: 423–37.
55 Lee S, Jun JK, Suh M, et al. Gastric cancer screening uptake trends
in Korea: results for the National Cancer Screening Program from
2002 to 2011: a prospective cross-sectional study. Medicine 2015;
94: e533.
56 Zheng X, Mao X, Xu K, et al. Massive endoscopic screening for
esophageal and gastric cancers in a high-risk area of China.
PLoS One 2015; 10: e0145097.
57 Lagergren J, Lagergren P. Recent developments in esophageal
adenocarcinoma. CA Cancer J Clin 2013; 63: 232–48.
58 Taylor PR, Abnet CC, Dawsey SM. Squamous dysplasia--the
precursor lesion for esophageal squamous cell carcinoma.
Cancer Epidemiol Biomarkers Prev 2013; 22: 540–52.
59 Abnet CC, Corley DA, Freedman ND, Kamangar F. Diet and upper
gastrointestinal malignancies. Gastroenterology 2015;
148: 1234–43.e4.
