Int. J. Cancer: 124, 1907–1913 (2009)
' 2008 Wiley-Liss, Inc.
Green tea drinking, high tea temperature and esophageal cancer in high- and
low-risk areas of Jiangsu Province, China: A population-based case–control study
Ming Wu1, Ai-Min Liu2, Ellen Kampman3, Zuo-Feng Zhang4, Pieter van’t Veer3, De-Lin Wu5, Pei-Hua Wang1, Jie Yang1,
Yu Qin1, Li-Na Mu6, Frans J. Kok3 and Jin-Kou Zhao1*
1
Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, China
2
Dafeng Center for Disease Control and Prevention, Dafeng, Jiangsu, China
3
Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands
4
Department of Epidemiology, School of Public Health, University of California, Los Angeles, CA
5
Ganyu Center for Disease Control and Prevention, Ganyu, Jiangsu, China
6
Department of Social and Preventive Medicine, School of Public Health and Health Professions,
University at Buffalo, The State University of New York, Buffalo, NY
Epidemiological studies suggested drinking green tea is inversely
associated with esophageal cancer but results remain inconclusive.
Moreover, inconsistent observations found high temperature
drinks are associated with esophageal cancer. A population-based
case–control study was conducted in a high-risk area (Dafeng) and
a low-risk area (Ganyu) of esophageal cancer in Jiangsu province
China from 2003 to 2007. It aimed to explore green tea drinking
and tea temperature with the risk of esophageal cancer, and to
compare the difference between different risk regions. Using identical protocols, 1,520 cases and 3,879 healthy controls were
recruited as study subjects in 2 regions. Detailed information was
collected to assess green tea drinking habits. Unconditional logistic
regression was used to obtain OR and 95% CI. Results showed
that ever drinking green tea elevated OR in both counties (Dafeng
OR 5 1.2, 95% CI 5 0.9–1.5; Ganyu: OR 5 1.9, 95% CI 5 1.4–
2.4). Drinking tea at high temperature was found to increase cancer risk in both areas (Dafeng: OR 5 1.9, 95% CI 5 1.2–2.9;
Ganyu OR 5 3.1 95% CI 5 2.2–4.3). However, after further
adjustment for tea temperature, ever drinking tea was not related
to cancer in either county (Dafeng: OR 5 1.0, 95% CI 5 0.7–1.3;
Ganyu: OR 5 1.3, 95% CI 5 0.9–1.7). For dose-response relationships, we observed positive relationship with monthly consumption of tea (p for trend 5 0.067) and tea concentration (p for
trend 5 0.006) after further adjustment for tea temperature. In
conclusion, green tea drinking was not inversely associated with
esophageal cancer in this study. However, drinking tea at high
temperatures significantly increased esophageal cancer risk.
There was no obvious difference of green tea drinking between
low- and high-risk areas.
' 2008 Wiley-Liss, Inc.
Key words: green tea; hot drinking; esophageal cancer; case–control
study; smoking; alcohol drinking
Esophageal cancer is the sixth most common cause of cancer
mortality worldwide. The number of new esophageal cancer cases in
China accounted for 53% of all new cases in the world in 2002. The
incidence and mortality rates (per 100,000) in China are 27.4 and
21.6 for men and 12.0 and 9.6 for women, respectively.1 Jiangsu
Province, located in South-Eastern China, is one of the highest incidence areas of the disease. According to the Second National Death
Cause Retrospective Survey, the mortality of esophageal cancer was
30 of 100,000 from 1990 to 1992 in Jiangsu province, much higher
than the national average of 17 of 100,000.2 Although the mortality
of esophageal cancer is high in most counties in Jiangsu; it differs
considerably between counties, despite their similar geographic
characteristics and socioeconomic status.3
Numerous epidemiological studies have demonstrated that environmental and lifestyle factors such as tobacco smoking, alcohol
drinking and dietary habits are associated with the development of
esophageal cancer.4,5 It is also suggested that the consumption of
green tea may help prevent esophageal cancer in humans.6,7 Tea is
currently grown in at least 30 countries, and it is the most frequently consumed beverage worldwide after water, especially in
Asian countries such as China, Japan and India.8 The per capita
Publication of the International Union Against Cancer
worldwide consumption of tea is approximately 120 ml brewed
tea per day.9 Depending on the manufacturing process, tea is classified into 3 major types: green tea (non-fermented), oolong tea
(half-fermented) and black tea (fermented). Green tea is derived
from Camellia sinesis, an evergreen shrub of the Theaceae family.
It contains many polyphenols known as cathechins, including epigallo-cathechin-3 gallate (EGCG), epigallo-cathechin (EGC) and
epicathechin-3 gallate (ECG).10 A number of studies have provided evidence that the polyphenolic antioxidants present in tea
may be capable of affording protection against cancer.11–13
A few epidemiological studies have addressed the association
between green tea and esophageal cancer, but results remain
inconclusive.14–17 Moreover, inconsistent observations suggest
that high-temperature drinks are associated with esophageal cancer.18 Since 2003, a population-based case–control study has been
conducted in selected high- and low-risk areas of esophageal cancer in Jiangsu, China. In this analysis, we evaluate the association
of esophageal cancer with green tea drinking and tea temperature
in high- and low-risk areas. The results may help us improve the
current understanding of the effects of green tea drinking and hightemperature drinking on the development of esophageal cancer.
Material and methods
Study areas
A population-based case–control study has been conducted in 2
counties of Jiangsu province, Dafeng and Ganyu from 2003 to
2007. Both Dafeng and Ganyu are less developed, coastal, rural
counties in northern Jiangsu province. The total population in
Dafeng and Ganyu are approximately 0.7 million and 1.1 million,
respectively. Dafeng has a higher mortality of esophageal cancer
than Ganyu. From 1996 to 2002, the yearly average age-adjusted
mortality of esophageal cancer was 36 of 100,000 in Dafeng, but
was 24 of 100,000 in Ganyu during the same period.19
Study subjects
All subjects were restricted to local inhabitants who have lived
in either area for at least 5 years. Newly diagnosed primary esophageal cancer patients from local adult residents were recruited as
cases, using the data from local population based cancer registry
agencies. The cancer registry agencies in both counties were
established in the late 1990s and are part of the local Center for
Disease Control and Prevention (CDC). All cases were identified
by International Classification of Diseases, 10th revision (ICD-10,
Grant sponsor: Jiangsu Provincial Health Department; Grant number:
RC 2003090.
*Correspondence to: No. 172 Jiangsu Road, Nanjing 210009, China.
Fax: 186-25-83759411. E-mail: [email protected]
Received 23 June 2008; Accepted after revision 21 October 2008
DOI 10.1002/ijc.24142
Published online 6 November 2008 in Wiley InterScience (www.interscience.
wiley.com).
1908
WU ET AL.
code C15). Second primary and recurrent cancers were excluded.
A system of rapid case recognition was used in the study. All regional hospitals were required by the local health authorities to
report new patients shortly after diagnosis. As the cancer registry
agencies are attached to local CDC, investigators from local
CDC could identify and interview the cases as quickly as possible. In this study, 68 and 75% of newly registered esophageal
cancer cases were identified and interviewed in Dafeng and
Ganyu, respectively. Because of the low proportion of pathological examination in less developed rural areas (Dafeng 61%,
Ganyu 30%), patients who were diagnosed by other sophisticated
methods such as endoscopic examination or radiology were also
included.
Controls were derived from the same county as cases. Eligible
controls were randomly selected from the general population,
using the data of the county demographic database. Controls and
cases were frequency matched by gender and age (65 years). Individuals with history of cancer were not eligible as controls. The
responding rate of control was 87% in Dafeng and 85% in Ganyu.
By study design, 600 cases and 600 controls in each county
were required for the study. For Dafeng and Ganyu, recruitment of
cases and controls was finished in 2006 and in 2007, respectively.
As identical case–control studies on stomach, liver and lung cancer were also conducted in these 2 counties at the same time, controls for all cancer sites were used in this analysis. In total, 1,520
cases (637 in Dafeng County and 883 in Ganyu County) and 3,879
controls (1,938 in Dafeng County and 1,941 in Ganyu County)
were recruited for this study.
weight and obese: low weight (BMI < 18.5), overweight (BMI 24 and BMI < 28), obesity (BMI 28).20
Chi-square and Student t-tests were used to compare the distribution of potential risk or protective factors among control groups
between the 2 counties. Unconditional logistic regression with a
maximum likelihood estimation of parameters was applied for
both univariate and multivariate analyses. The strength of the
association was quantified as odds ratios (OR), and 95% confidence intervals (CI) around the OR were used to quantify precision. Dummy variables were used in the logistic regression to estimate OR for each exposure category. The trend test of ordered
variables was performed by assigning scores to different exposure
levels and treated the categorical variable as a continuous variable
in the logistic regression model. Effect modification was analyzed
by stratification. Statistical interaction was assessed by including
main effect variables and their product terms in the logistic regression model.
On the basis of prior knowledge and confounding assessment,
the effect of green tea was evaluated adjusting for age (continuous), gender (female 5 0, male 5 1), education level (ordered),
income 10 years before (continuous), cancer family history of first
degree relatives (No 5 0, yes 5 1), BMI (continuous), pack-years
of smoking (continuous) and alcohol drinking (never or seldom 5
0, often 5 1). The effect after further adjustment for tea temperature
was also presented (never drinker and normal tea temperature 5 0,
high tea temperature 5 1).
Results
Data collection
Using standard protocols and a pretested standardized epidemiologic questionnaire, with written informed consent, we collected epidemiological data by face-to-face interviews in both
counties. Five milliliters of blood samples were collected at the
time of interview.
The questionnaire included detailed information on known or
potential risk or protective factors for esophageal cancer, including demographic information, socio-economic status, living conditions, environmental exposure, tobacco smoking, alcohol drinking,
dietary habits, disease history, etc. Ever drinking green tea was
defined as drinking at least 1 cup of green tea per week for more
than 6 months. We collected lifetime general consumption of
green tea drinking, and change of drinking pattern one year before
diagnosis for cases or one year before interview for controls.
Details of tea drinking habits included drinking status (current,
former or never drinking), age when the person began to drink tea
regularly, number of years drinking tea, monthly consumption of
tea (grams/month), tea concentration and temperature of the water
(boiling or not boiling) used to brew tea at the time of drinking.
To validate the variables above, the questionnaire also collected
information about the number of new cups of tea made each day
(times the person changed the leaves in the tea cup), subsequent
brewing of each cup (times the person poured new water into each
cup without changing leaves).
In the rural areas of Jiangsu Province, China, seldom do people
drink oolong tea or coffee, therefore, we did not include information on these 2 beverages in the questionnaire.
Statistical analysis
Data were entered into the computer by Epidata 2.1b, cleansed
and analyzed using SAS v8.2 software. In the analysis, ever drinking green tea was further categorized into former drinking and current drinking; individuals who quit drinking because of health reasons but quit in less than 1 year at the time of interview were considered current drinkers. Smoking was categorized into ever
smoking and never smoking. Pack-years of smoking were also calculated. Alcohol drinking was categorized into never or seldom
drinking and often drinking. For body mass index (BMI), the Chinese recommended standard was used for the definition of over-
The demographic characteristics of cases and controls are
shown by county in Table I, together with socio-economic related
variables, cancer family history of first degree relatives, as well as
smoking and alcohol drinking status.
Comparing the 2 counties, Ganyu has a higher proportion of
male cases than Dafeng. Ganyu also has a lower educational level
and lower previous income than Dafeng, as well as a lower prevalence of cancer family history (p < 0.01). Prevalence of smoking
and green tea drinking in Dafeng is much lower than in Ganyu
(p < 0.01). Although alcohol drinking appears to be higher in
Dafeng, the difference was not statistically significant (p 5 0.18).
Within both counties, cases were older and more often male.
The OR and 95% CI for esophageal cancer with socio-economic
status, cancer family history, smoking and alcohol drinking were
also shown in Table I. Cases more frequently occurred in the population with lower socio-economic statuses, i.e., lower education
level, lower previous income, and lower BMI. Cancer family history in first-degree relatives was found to significantly increase the
risk of esophageal cancer (OR: Dafeng 5 1.4, Ganyu 5 2.1). An
increased risk was observed among smokers in both counties (OR:
Dafeng 5 1.4, Ganyu 5 1.5) as compared to nonsmokers. An
apparent dose-response relationship was also found between
esophageal cancer and pack-years of smoking (p for trend <
0.05). Similar to smoking, people who often drink alcohol tend to
have a higher risk of esophageal cancer (OR: Dafeng 5 1.3,
Ganyu 5 1.6) as compared to those who never or seldom drink
alcohol.
Table II shows the association between esophageal cancer and
green tea drinking in each county. After adjusting for potential
confounders including age, gender, education level, previous
income, cancer family history, BMI, pack-years of smoking and
alcohol drinking, we found that ever drinking green tea significantly increased esophageal cancer risk in Ganyu (OR 5 1.9, 95%
CI 5 1.4–2.4), but it was not significant in Dafeng (OR 5 1.2,
95%CI 5 0.9–1.5). Former drinking was observed to be strongly
associated with increasing OR in both counties (Dafeng: OR 5
3.4, 95% CI 5 1.9–6.1; Ganyu: OR 5 6.4, 95% CI 5 3.6–11.5),
whereas for current drinking, increased risk was found in Ganyu
(OR 5 1.6, 95% CI 5 1.2–2.1) but not in Dafeng (OR 5 1.0, 95%
CI 5 0.8–1.3). Tea temperature was found to be positively related
1909
GREEN TEA DRINKING, TEA TEMPERATURE, ESOPHAGEAL CANCER
TABLE I – DEMOGRAPHIC INFORMATION AND EPIDEMIOLOGIC CHARACTERISTICS OF STUDY SUBJECTS IN HIGH AND LOW RISK AREAS
Dafeng (High)
Case (%)
(N 5 637)
Control (%)
(N 5 1,938)
Gender
Males
426 (66.9)
1,368 (70.6)
Females
211 (33.1)
570 (29.4)
Age
Mean 6 SD (years)
65.4 6 9.0
63.6 6 11.0
<50
26 (4.1)
227 (11.7)
50–60
131 (20.6)
401 (20.7)
60–70
266 (41.8)
681 (35.1)
70–80
177 (27.8)
525 (27.1)
80
37 (5.8)
104 (5.4)
Education level
Illiteracy
338 (53.1)
827 (42.7)
Primary school
214 (33.6)
703 (36.3)
Middle school and above
85 (13.3)
407 (21.0)
p for trend
Income 10 years ago
Mean 6 SD
1,792 6 2,026 2,293 6 2,366
<1,000
148 (23.3)
266 (13.8)
1,000–1,500
123 (19.3)
353 (18.3)
1,500–2,500
194 (30.5)
589 (30.6)
>2,500
171 (27.0)
718 (37.3)
p for trend (continuous)
Body Mass Index (BMI)3
Mean 6 SD
20.8 6 3.7
22.7 6 6.0
Low (<18.5)
162 (25.5)
174 (9.0)
Normal (18.5–23.9)
381 (60.0)
1,175 (60.7)
Overweight (24–27.9)
73 (11.5)
471 (24.3)
Obesity (>528)
19 (3.0)
115 (5.9)
p for trend (continuous)
Cancer family history (First degree relatives)
No
348 (54.4)
1,178 (60.8)
Yes
289 (45.4)
760 (39.2)
Smoking status
Never smoke
200 (31.4)
817 (42.2)
Ever smoke
437 (68.6)
1,121 (57.8)
Pack-years of smoking
Never smoker
200 (31.4)
817 (42.2)
<30 years
187 (29.6)
554 (28.6)
>530 years
250 (39.2)
567 (29.3)
p for trend (continuous)
Alcohol drinking status
Never or seldom
354 (55.6)
1,158 (59.8)
Often drinking
283 (44.4)
780 (40.2)
Ganyu (Low)
OR (95% CI)
Case (%)
(N 5 883)
Control (%)
(N 5 1,941)
765 (86.6)
118 (11.4)
1,548 (79.8)
393 (20.2)
66.0 6 9.9
42 (4.8)
201 (22.8)
281 (31.8)
288 (32.6)
71 (8.0)
65.1 6 11.3
165 (8.5)
426 (22.0)
563 (29.0)
632 (32.6)
155 (8.0)
1.0 (referent)
0.8 (0.6–1.0)
0.6 (0.4–0.8)
<0.001
558 (63.3)
230 (26.1)
94 (10.7)
1,230 (63.4)
467 (24.1)
243 (12.5)
1.0 (referent)
1.1 (0.9–1.3)
0.9 (0.6–1.2)
0.689
1.0 (referent)2
0.7 (0.5–1.0)
0.6 (0.5–0.8)
0.5 (0.4–0.7)
<0.001
1,493 6 1,812
313 (36.2)
190 (22.0)
203 (23.5)
158 (18.3)
1,773 6 1,953
632 (33.4)
394 (20.8)
444 (23.4)
424 (22.4)
1.0 (referent)2
1.0 (0.8–1.3)
1.0 (0.8–1.2)
0.8 (0.6–1.0)
0.062
1.0 (referent)2
2.8 (2.2–3.6)
0.5 (0.4–0.6)
0.5 (0.3–0.9)
<0.001
22.2 6 4.0
78 (8.9)
636 (72.8)
125 (14.3)
35 (4.0)
22.9 6 3.6
104 (5.4)
1,318 (68.2)
431 (22.3)
80 (4.1)
1.0 (referent)2
1.5 (1.1–2.1)
0.6 (0.5–0.8)
1.0 (0.7–1.6)
<0.001
1.0 (referent)2
1.4 (1.1–1.6)
730 (82.7)
153 (17.3)
1,759 (90.6)
182 (9.4)
1.0 (referent)2
2.1 (1.6–2.6)
1.0 (referent)4
1.4 (1.1–1.8)
215 (24.4)
668 (75.6)
732 (37.7)
1,209 (62.3)
1.0 (referent)4
1.5 (1.2–1.9)
1.0 (referent)4
1.2 (1.0–1.6)
1.6 (1.3–2.1)
0.029
215 (24.4)
427 (48.4)
241 (33.4)
732 (37.7)
852 (43.9)
357 (18.4)
1.0 (referent)4
1.4 (1.1–1.8)
1.8 (1.4–2.4)
0.011
1.0 (referent)4
1.3 (1.0–1.6)
417 (47.2)
466 (52.8)
1,200 (61.8)
741 (38.2)
1.0 (referent)4
1.6 (1.3–1.9)
–
–
OR (95% CI)
p-Value1
–
<0.01
–
<0.01
<0.01
<0.01
0.27
<0.01
<0.01
<0.01
0.18
1
p-Value for comparing control groups between two counties.–2Adjusted for age (continuous) and gender.–3Chinese recommend standard
was used for the definition of overweight and obesity: low weight (BMI < 18.5), overweight (BMI>5 24 and BMI < 28), obesity (BMI >5
28).–4Adjusted for age (continuous), gender, education level, income 10 years before (continuous), cancer family history and BMI (continuous).
to esophageal cancer risk in both counties, OR of drinking tea at
high temperature was 1.9 in Dafeng (95% CI 5 1.2–2.9) and 3.1
in Ganyu (95% CI 5 2.2–4.3), as compared to never drinkers.
When further adjusted tea temperature in the logistic regression
model, we found ever drinking tea was not significantly related to
esophageal cancer in either county (Dafeng: OR 5 1.0, 95% CI 5
0.7–1.3; Ganyu: OR 5 1.3, 95% CI 5 0.9–1.7). A positive association was still found in the former drinking group after adjusting
tea temperature (Dafeng: OR 5 2.2, 95% CI 5 1.6–5.3; Ganyu:
OR 5 4.2, 95% CI 5 2.3–7.6), but no significant association was
observed among current green tea drinkers in either Dafeng or
Ganyu.
Dose-response relationships for esophageal cancer risk with
green tea-drinking related variables such as age at starting drinking, years of drinking, monthly consumption of tea (grams/month)
and tea concentration were explored by county (Table II). We
found earlier age at starting drinking, long years of drinking,
higher grams of monthly tea consumption and high tea concentration were positively associated with cancer risk in both counties,
though the trends were more apparent in Ganyu. However, after
further adjustment for tea temperature, we only observed a positive dose-response relationship with monthly consumption of tea
(p for trend 5 0.014), and a borderline positive relationship with
tea concentration (p for trend 5 0.059) in Ganyu. No other apparent dose-response relationships were found.
Table III shows the effects of green tea drinking and doseresponse relationships among the former drinking, current drinking group and their combination (ever drinking). As we did not
find big difference between 2 counties (data not shown) and limited by the page width, pooled results of 2 counties are presented.
In the former drinking group, green tea drinking significantly
increased ORs despite the tea temperature. In the current drinking
group, drinking in normal temperature did not increase the cancer
risk (OR 5 0.9, 95% CI 5 0.8–1.2), but hot drinking elevated OR
significantly (OR 5 2.1, 95% CI 5 1.6–2.8). Similar results were
found in the ever drinking group, high tea temperature was found
significantly increased OR (OR 5 2.5, 95% CI 5 1.9–3.2) but normal temperature did not (OR 5 1.1, 95% CI 5 0.9–1.3).
Positive dose-response relationships were observed among former drinkers. Earlier age at starting drinking, long years of drinking, higher monthly consumption of tea and high tea concentration
were found increasing ORs. Similar positive relations among the
current drinking group were observed only before adjusting for tea
temperature. For ever drinking, we found higher monthly con-
TABLE II – THE OR AND 95% CI OF ESOPHAGEAL CANCER RISK WITH GREEN TEA DRINKING IN HIGH- AND LOW- RISK AREAS
Dafeng (High)
Variables
Case/Control
Green tea drinking
Never drinking
467/1,401
Ever drinking
170/537
Former drinking
33/42
Current drinking
137/495
Tea temperature
Never drinking
467/1,401
Normal temperature
118/431
High temperature
51/103
Age at tea drinking start
Never drinking
467/1,401
<25
20/79
25–34
53/151
35–44
37/105
45
58/202
p value for trend
Years of tea drinking
Never drinking
467/1,401
<20 years
65/238
20–34 years
57/176
35 years
45/123
p value for trend
Monthly consumption of tea (g/month)
Never drinking
467/1,401
1–149 g
109/382
150–249 g
29/88
250 g
27/62
p value for trend
Tea concentration
Never drinking
467/1,401
Low
29/152
Moderate
75/243
High
66/142
p value for trend
Ganyu (Low)
OR1 (95% CI)1
OR2 (95% CI)2
Case/Control
OR1 (95% CI)1
OR2 (95% CI)2
1.0 (referent)
1.2 (0.9–1.5)
3.4 (1.9–6.1)
1.0 (0.8–1.3)
1.0 (referent)
1.0 (0.7–1.3)
2.2 (1.6–5.3)
0.8 (0.6–1.1)
–
384/1,132
499/809
95/44
404/765
1.0 (referent)
1.9 (1.4–2.4)
6.4 (3.6–11.5)
1.6 (1.2–2.1)
1.0 (referent)
1.3 (0.9–1.7)
4.2 (2.3–7.6)
1.1 (0.8–1.5)
–
384/1,132
244/553
252/248
1.0 (referent)
1.3 (0.9–1.7)
3.1 (2.2–4.3)
1.0 (referent)
1.0 (0.7–1.3)
1.9 (1.2–2.9)
1.0 (referent)
1.0 (0.6–1.8)
1.4 (1.0–2.2)
1.4 (0.9–2.2)
0.9 (0.6–1.4)
0.543
1.0 (referent)
0.8 (0.4–1.5)
1.2 (0.8–1.8)
1.2 (0.7–1.9)
0.8 (0.6–1.2)
0.701
384/1,132
117/177
255/374
77/164
44/90
1.0 (referent)
1.8 (1.2–2.6)
1.9 (1.4–2.6)
1.6 (1.0–2.6)
1.3 (0.6–2.6)
<0.001
1.0 (referent)
1.2 (0.8–1.9)
1.3 (1.0–1.9)
1.1 (0.7–1.8)
0.9 (0.4–1.9)
0.469
1.0 (referent)
1.1 (0.8–1.5)
1.1 (0.7–1.6)
1.4 (0.9–2.1)
0.161
1.0 (referent)
1.0 (0.6–1.4)
0.9 (0.6–1.4)
1.1 (0.7–1.8)
0.817
384/1,132
51/146
227/330
209/325
1.0 (referent)
1.2 (0.7–2.0)
2.0 (1.5–2.8)
1.6 (1.2–2.3)
<0.001
1.0 (referent)
0.8 (0.5–1.5)
1.4 (1.0–2.0)
1.1 (0.8–1.6)
0.189
1.0 (referent)
1.1 (0.8–1.4)
1.3 (0.8–2.1)
1.4 (0.8–2.6)
0.140
1.0 (referent)
1.0 (0.7–1.3)
1.0 (0.6–1.8)
1.0 (0.6–2.0)
0.926
384/1,132
117/244
111/185
264/361
1.0 (referent)
1.5 (1.0–2.3)
1.4 (1.0–2.1)
2.2 (1.7–3.0)
<0.001
1.0 (referent)
1.1 (0.7–1.7)
1.0 (0.7–1.6)
1.6 (1.1–2.2)
0.014
1.0 (referent)
0.7 (0.4–1.1)
1.1 (0.8–1.6)
1.7 (1.2–2.5)
0.016
1.0 (referent)
0.6 (0.4–1.0)
1.0 (0.7–1.4)
1.4(0.9–2.1)
0.235
384/1,132
53/137
273/452
171/213
1.0 (referent)
1.3 (0.8–2.3)
1.7 (1.2–2.3)
2.4 (1.7–3.4)
<0.001
1.0 (referent)
1.0 (0.6–1.7)
1.3 (0.9–1.8)
1.4 (0.9–2.1)
0.059
1
Adjusted for age (continuous), gender, education level, income 10 years before (continuous), cancer family history, BMI (continuous), packyear of smoking (continuous), alcohol drinking.–2Adjusted for above mentioned variables, further adjusted for tea temperature (never drinker
and normal temperature 5 0, high temperature 5 1).
TABLE III – THE OR AND 95% CI OF ESOPHAGEAL CANCER RISK WITH GREEN TEA DRINKING IN DIFFERENT GROUPS IN HIGH- AND LOW-RISK AREAS
Variables
Former drinking
OR1 (95% CI)1
Tea temperature
Never drinking
1.0 (referent)
Normal temperature
3.2 (2.0–5.1)
High temperature
10.2 (4.8–21.6)
Age at tea drinking start
Never drinking
1.0 (referent)
<25
5.4 (2.4–12.4)
25–34
6.4 (3.4–12.3)
35–44
4.4 (1.7–11.1)
45
2.1 (0.9–5.0)
p value for trend
<0.001
Years of tea drinking
Never drinking
1.0 (referent)
<20 years
3.0 (1.5–5.8)
20–34 years
5.0 (2.8–9.1)
35 years
6.8 (3.0–15.7)
p value for trend
<0.001
Monthly consumption of tea leaves (g/month)
Never drinking
1.0 (referent)
1–149 g
3.9 (2.3–6.8)
150–249 g
3.4 (1.3–8.4)
250 g
7.4 (3.5–15.5)
p value for trend
<0.001
Tea concentration
Never drinking
1.0 (referent)
Low
2.1 (1.0–4.8)
Moderate
3.9 (2.3–6.7)
High
14.9 (5.8–38.1)
p value for trend
<0.001
Current drinking
OR2 (95% CI)2
OR1 (95% CI)1
–
OR2 (95% CI)2
Ever drinking3
OR1 (95% CI)1
–
1.0 (referent)
0.9 (0.8–1.2)
2.1 (1.6–2.8)
OR2 (95% CI)2
–
1.0 (referent)
1.1 (0.9–1.3)
2.5 (1.9–3.2)
1.0 (referent)
3.1 (1.2–7.9)
4.6 (2.3–9.3)
3.1 (1.2–8.2)
1.6 (0.7–4.1)
0.003
1.0 (referent)
1.2 (0.9–1.7)
1.5 (1.1–1.9)
1.3 (0.9–1.8)
0.9 (0.6–1.2)
0.276
1.0 (referent)
0.9 (0.6–1.3)
1.1 (0.8–1.4)
1.0 (0.7–1.4)
0.7 (0.5–1.0)
0.241
1.0 (referent)
1.4 (1.0–1.9)
1.7 (1.3–2.1)
1.4 (1.0–2.0)
1.0 (0.7–1.3)
0.100
1.0 (referent)
1.0 (0.8–1.5)
1.2 (1.0–1.6)
1.1 (0.8–1.5)
0.8 (0.6–1.1)
0.172
1.0 (referent)
2.3 (1.2–4.7)
3.6 (1.9–6.5)
3.9 (1.5–10.0)
<0.001
1.0 (referent)
0.9 (0.66–1.2)
1.3 (1.01–1.7)
1.3 (1.01–1.7)
0.009
1.0 (referent)
0.7 (0.52–1.0)
1.0 (0.74–1.3)
1.0 (0.73–1.3)
0.965
1.0 (referent)
1.1 (0.79–1.42)
1.5 (1.17–1.88)
1.5 (1.14–1.91)
0.404
1.0 (referent)
0.9 (0.6–1.2)
1.1 (0.9–1.4)
1.1 (0.8–1.4)
0.666
1.0 (referent)
3.0 (1.6–5.4)
2.6 (1.0–6.9)
4.4 (1.9–10.3)
0.043
1.0 (referent)
1.0 (0.75–1.24)
1.2 (0.88–1.69)
1.8 (1.36–2.31)
<0.001
1.0 (referent)
0.8 (0.6–1.0)
0.9 (0.6–1.3)
1.3 (1.0–1.8)
0.206
1.0 (referent)
1.2 (0.9–1.5)
1.3 (1.0–1.8)
2.0 (1.5–2.5)
0.023
1.0 (referent)
1.0 (0.7–1.2)
1.0 (0.7–1.4)
1.4 (1.1–1.9)
0.067
1.0 (referent)
1.8 (0.8–4.2)
2.9 (1.6–5.4)
9.7(3.5–26.7)
<0.001
1.0 (referent)
0.8 (0.5–1.1)
1.2 (0.9–1.5)
1.6 (1.3–2.2)
<0.001
1.0 (referent)
0.6 (0.4–0.9)
1.0 (0.8–1.2)
1.1(0.8–1.5)
0.212
1.0 (referent)
0.9 (0.6–1.2)
1.3 (1.1–1.7)
1.9 (1.5–2.4)
<0.001
1.0 (referent)
0.7 (0.5–1.0)
1.1 (0.9–1.4)
1.3 (1.0–1.8)
0.006
1
Adjusted for age (continuous variable), gender, education level, income 10 years before (continuous variable), cancer family history, BMI
(continuous variable), pack-year of smoking (continuous variable), alcohol drinking and counties.–2Adjusted for above mentioned variables, further adjusted for tea temperature (never drinker and normal temperature 5 0, high temperature 5 1).–3Ever drinking is the combination o former
drinking and current drinking.
1911
GREEN TEA DRINKING, TEA TEMPERATURE, ESOPHAGEAL CANCER
TABLE IV – THE EFFECT MODIFICATION OF ESOPHAGEAL CANCER
RISK BETWEEN GREEN TEA DRINKING AND SMOKING, PACK-YEARS
OF SMOKING, ALCOHOL DRINKING
TABLE V – THE EFFECT MODIFICATION OF ESOPHAGEAL CANCER RISK
BETWEEN HIGH TEA TEMPERATURE AND SMOKING, PACK-YEARS OF
SMOKING, ALCOHOL DRINKING
High tea temperature1
Green tea drinking
Never
Former
Current
1
Ever-smoking
No
1.0 (referent)
Yes
1.3 (1.1–1.6)
p-Value for
0.058
interaction
Pack years of smoking1
<30
1.0 (referent)
>530
1.4 (1.1–1.6)
p-Value for
0.224
interaction
2
Alcohol drinking
No
1.0 (referent)
Yes
1.2 (0.9–1.5)
p-Value for
0.450
interaction
No
Yes
1.0 (referent)
1.4 (1.2–1.7)
0.459
1.9 (1.2–2.9)
3.2 (2.5–4.0)
1.0 (referent)
1.4 (1.2–1.7)
0.253
2.1 (1.7–2.6)
3.6 (2.6–4.8)
1.0 (referent)
1.2 (1.0–1.5)
0.616
2.2 (1.5–3.3)
3.2 (2.3–4.2)
2
1.6 (0.8–3.2)
5.2 (3.6–7.5)
0.7 (0.5–0.9)
1.3 (1.0–1.6)
3.1 (2.1–4.6)
5.2 (3.1–8.7)
0.9 (0.7–1.0)
1.4 (1.1–1.8)
1.9 (0.9–3.9)
5.0 (3.0–8.4)
0.8 (0.6–1.1)
1.1 (0.9–1.5)
1
Adjusted for age (continuous), gender, education level, income 10
years before (continuous), cancer family history, BMI (continuous),
alcohol drinking, tea temperature (never drinker and normal temperature 5 0, high temperature 5 1) and counties.–2Adjusted for age (continuous), gender, education level, income 10 years before (continuous),
cancer family history, BMI (continuous), pack-year of smoking (continuous), tea temperature (never drinker and normal temperature 5 0,
high temperature 5 1) and counties.
sumption of tea (p for trend 5 0.067) and usually drinking tea in
high concentration (p for trend 5 0.006) showed a positive tendency with cancer risk after adjusting for tea temperature.
Effect modification between green tea drinking and smoking
status, pack-years of smoking, and alcohol drinking were evaluated by stratified analysis, pooled results of 2 counties are shown
in Table IV. Former drinking individuals who had smoked, or had
pack-years of smoking larger than 30, or had often drunk alcohol
have the highest risk of esophageal cancer, but the interactions
were not statistically significant.
Table V shows the effect modification of hot drinking by smoking status, pack-years of smoking and alcohol drinking. Additive
effects were found between drinking tea at high temperature and
ever smoking, pack-years of smoking and ever drinking alcohol.
The highest ORs were among hot drinking individuals who had
smoked, or had pack-years of smoking larger than 30, or had often
drunk alcohol, but these effect modifications were not statistically
significant again.
Discussion
This population-based case–control study, conducted in highand low-risk areas of Jiangsu Province, China explored the association between green tea, hot tea drinking and esophageal cancer.
Compared to previous studies, this study has the largest sample
size and has addressed the association in different risk areas simultaneously. In the presented analysis; however, no obvious association between green tea drinking and esophageal cancer was
observed in either high- or low- risk areas. On the contrary, drinking tea at high temperature was significantly related to the occurrence of esophageal cancer consistent in both high and low risk
counties.
Green tea has been considered an herb medicine and a healthy
beverage since ancient times. It is considered as a potential cancer
preventive agent on the basis of numerous in vitro, in vivo and epidemiological studies.11–15 It has been suggested that the anti-oxidative and anti-inflammatory properties of green tea make it a
promising agent for human cancer prevention.6 Tea polyphenols
are known to be strong antioxidants. Cao et al. reported that green
tea even has a much higher antioxidant activity against peroxyl
radicals than some vegetables.21
Ever-smoking
No
Yes
p-Value for interaction
Pack years of smoking2
<30
>530
p-Value for interaction
Alcohol drinking3
No
Yes
p-Value for interaction
1
No, never drinker and normal tea temperature; Yes, drinking tea in
high tea temperature.–2Adjusted for age (continuous variable), gender,
education level, income 10 years before (continuous variable), cancer
family history, BMI (continuous variable), alcohol drinking and counties.–3Adjusted for age (continuous variable), gender, education level,
income 10 years before (continuous variable), cancer family history,
BMI (continuous variable), pack-year of smoking (continuous variable) and counties.
Only a few studies have reported the relationship between green
tea drinking and esophageal cancer with conflicting results. Some
case–control studies carried out in Jiangsu and Shanghai, China,
reported inverse association.14,15,22,23 Gao et al. found that green
tea drinking reduced the risk of esophageal cancer among women
(OR 5 0.50, 95% CI 5 0.30–0.83) in Shanghai, and this risk
decreased as tea consumption increased (p for trend < 0.01); the
OR were also below 1.00 among men but were not statistically
significant.14 Wang et al. reported that green tea drinking showed
a protective effect in women (OR 5 0.26; 95% CI 5 0.07–0.94)
in Jiangsu, but no dose-response relationship was found for teadrinking duration.15 Another case–control study was also conducted in Jiangsu did not find an obvious protective effect.16 An
intervention trial was conducted in Henan, another high risk province of China, where subjects with esophageal precancerous
lesions were supplemented with decaffeinated green tea (DGT)
5 mg/day for 12 months. The results did not show an apparent difference between treatment and placebo groups.24 In consistent
with our study, some studies conducted in western country also
reported no association between tea drinking and esophageal
cancer. Tavani reported OR 5 0.9 (95% CI 5 0.7–1.2) in a hospital-based case control study.25 La Vecchia found no association
(RR 5 1.0, 95% CI 5 0.7–1.4) in another study in Italy.26
In this study, ever drinking green tea was positively associated
with esophageal cancer risk in both low- and high-risk areas
(Dafeng: OR 5 1.2, 95% CI 5 0.9–1.5; Ganyu OR 5 1.9, 95%
CI 5 1.4–2.4). But after further adjusting for tea temperature, no
significant association was observed either in Dafeng (OR 5 1.0,
95% CI 5 0.7–1.3) or in Ganyu (OR 5 1.3, 95% CI 5 0.9–1.7).
Drinking beverages at high temperatures has been suggested as a
cause of esophageal cancer by a number of studies.18 Hot drinking
can cause thermal injury of esophageal mucosa and make it more
susceptible to carcinogenesis. Our findings show that drinking tea
at high temperatures had a 1.9- and 3.1-fold elevated risk in
Dafeng and Ganyu. Additive effects between hot tea drinking and
smoking, pack-years of smoking, as well as alcohol drinking were
also observed in our study. Individuals who drank green tea at a
high temperature, but who also smoked cigarettes or drank alcohol
had the highest odds ratio for esophageal cancer, although the
effect modifications were not statistically significant.
Kinjo et al. reported similar associations in a cohort study, the
rate ratio was 1.6 (95% CI 5 1.2–2.0) for hot tea (drinking green
tea at high temperature) in comparison with non-hot tea (drinking
green tea at moderate temperature).27 Another pooled analysis of
1912
WU ET AL.
2 prospective cohorts in Japan found that as compared to never
drinkers, drinking 5 cups of green tea/day significantly
increased the risk of esophageal cancer (HR 5 1.67, p for trend 5
0.04). The population attributable fraction of esophageal cancer
incidence attributed to green tea consumption was 22.1%, but as
mentioned by the author, tea temperature could be a plausible explanation for the increased OR.17 Some cohort studies and case–
control studies reported no association for hot drinks.28–30 In this
population-based case–control study with relatively large sample
size, we observed a strong association between drinking tea at a
high-temperature and esophageal cancer.
We observed substantially elevated ORs in the former drinking
group in 2 counties (Dafeng: OR 5 2.2, Ganyu: OR 5 4.2), even after adjusting for tea temperature. However, no significant association
was found for current drinkers in either Dafeng (OR 5 0.8) or
Ganyu (OR 5 1.1). This could be explained by cases who may be
more likely to quit drinking tea because of early digestive tract
symptoms. This higher proportion of former tea drinkers among
cases may have caused an inflated OR in the former drinking group.
However, in the current drinking group, the proportion of tea
drinkers was lower than the fact because some cases quit drinking at
an early time before disease onset, therefore the association might
have been underestimated in this group. We even found that ORs
were significantly changed if we used the combination of never
drinkers and former drinkers as a reference group, then compared
them with current drinkers (Dafeng: OR 5 0.74, 95% CI 5 0.54–
0.99; Ganyu OR 5 0.84, 95% CI 5 0.63–1.22), but this change was
attributed to potential bias. Therefore, how to avoid this kind of information bias should be carefully considered in future studies. In
the presented analysis, as few numbers of former drinkers, the results
of current drinking are more close to the real associations. The
results of ever drinking (combination of former and current drinking)
are similar to those in the current drinking group, and could be a better way to estimate the real associations.
After adjusting for potential confounders and tea temperature,
earlier age at starting drinking, long drinking years, higher amount
and higher concentration of tea drinking increased ORs apparently
in the former drinking group; no clear tendency was observed in
current drinkers, but again, there was a possibility of overestimation or underestimation of ORs in the former drinking and current
drinking groups, respectively. When former and current drinking
are combined together, positive dose-response trends were found
with higher monthly consumption of tea (p for trend 5 0.067) and
high tea concentration (p for trend 5 0.006) even after adjustment
for tea temperature. A plausible explanation is drinking green tea
is often accompanied by tobacco smoking and alcohol drinking
among the Chinese population, people who frequently drink a
high concentration of green tea are often heavy smokers or alcohol
drinkers.31 Mu et al. reported a more than multiplicative interac-
tion between green tea drinking and alcohol drinking (OR 5 4.57;
95% CI 5 1.62–12.89) in a study on stomach cancer.32 However,
smoking and alcohol drinking were not observed as significant
effect modifiers to tea drinking in the present study.
Several methodological issues need to be discussed. Potential
selection bias and information bias may exist in any case–control
study. A population-based study design and a random control
selection method were used to minimize selection bias in our
study. Cases were identified from the cancer registry data rather
than from certain hospitals, controls were randomly selected from
the county population demographic database, the response rate of
cases and controls were 68 and 87% in Dafeng, 75 and 85% in
Ganyu respectively. To reduce information bias, investigators
were well trained to collect epidemiologic data in detail. Moreover, green tea related variables such as tea temperature, drinking
years, monthly consumption of tea and tea concentration were
also investigated and analyzed to avoid misclassification of exposure.
Confounding also has been considered in our analysis. Although
the frequency matching method was applied in the study, controls
for stomach, liver and lung cancers were also used in the present
analysis. Therefore, differences of age and gender between case
and control group were enlarged and might cause residual confounding, even after adjusting them in the logistic regression
model. When sensitivity analysis was carried out with only esophageal cancer cases and their matched controls, the results were
similar as for the overall analysis, the OR and 95% CI of former
drinking and current drinking green tea was 2.2 (1.0–4.6) and 0.7
(0.5–1.0) in Dafeng, 3.6 (1.7–7.7) and 1.3 (0.9–1.8) in Ganyu, after adjusting for confounders and tea temperature.
There might be differences in the etiological factors between
esophageal adenocarcinoma and squamous cell carcinoma.
Because of the low pathological examination rate in less developed rural counties, it is difficult to differentiate between the subtypes of esophageal cancer in this population-based study. However, it has been reported that esophageal squamous-cell carcinoma represents more than 95% of esophageal cancer cases in
China.33
In conclusion, green tea drinking was not inversely associated
with esophageal cancer in this study in Jiangsu province, China.
However, drinking tea at high temperatures is strongly associated
with esophageal cancer. There was no obvious difference for the
effects of green tea drinking between low- and high-risk areas.
Acknowledgements
The authors thank the staffs of local Health Bureau and local
CDC in Dafeng and Ganyu County, for their assistance in field
works.
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