Letters to the Editor / Lung Cancer 78 (2012) 167170 169

Coffee and tea consumption and risk of lung cancer: A doseresponse analysis of observational studies
a r t i c l e i n f o
Keywords:
Tea
Coffee
Lung cancer
Doseresponse analysis
a b s t r a c t
Results from the recent meta-analysis suggested a favorable effect of green tea consumption and risk
of lung cancer, while no signicant association was found between black tea consumption and risk of
lung cancer. Besides, a signicantly positive association was found between coffee consumption and
risk of lung cancer. However, the relationship of green tea and coffee consumption is unclear. Thus the
doseresponse relationship was assessed by restricted cubic spline model and multivariate random-
effect meta-regression. Results suggested that a linear doseresponse relationship exists between coffee
consumption and risk of lung cancer, while the doseresponse relationship is nonlinear between green
tea consumption and risk of lung cancer.
2012 Elsevier Ireland Ltd. All rights reserved.
To the Editor,
Results fromthe meta-analysis by Tang et al. [1] in 2009 showed
an interesting result that an inverse relation was found between
green tea consumption and lung cancer risk [compared to the low-
est quantile, the relative risk (RR) and 95% condence interval
(CI) for the highest quantile of green tea consumption was 0.78
(0.611.00)]. But the association was not signicant for black tea
[compared to the lowest quantile, RR (95%CI) =0.86 (0.701.05) for
the highest quantile of black tea consumption]. When assuming
a linear relationship without performing a formal test, the RR for
an increase of two cups per day was 0.82 (0.710.96) and 0.82
(0.651.03) for green tea and black tea, respectively. The meta-
analysis by Tang et al. [2] in 2010 showed a signicant association
between coffee consumption and increased risk of lung cancer
[compared to the lowest quantile, RR (95%CI) =1.27 (1.041.54)
for the highest quantile of coffee consumption], and the RR for
an increase of two cups per day was 1.14 (1.041.26). This inves-
tigation has much practical implication regarding the prevention
and control of lung cancer. However, we would like to drawatten-
tion to the type of doseresponse relationship between green tea
and coffee consumption, and the possibility that green tea and
coffee consumption might have a threshold effect on the risk of
lungcancer, because a linear associations inepidemiologic research
can rarely be assumed a priori [3]. Besides, categories of green tea
and coffee consumption differed between studies, which might
complicate the interpretation of the pooled results across study
populations with different categories. In order to derive a summary
risk estimate for a standardized increase and specic exposure
values for green tea and coffee consumption, a doseresponse
meta-analysis with restricted cubic spline functions provides a
solution to the problem[3].
A comprehensive literature search was performed to July
2012 using the databases of Pubmed, Web of Knowledge,
China National Knowledge Infrastructure, China Biology Medical
literature database, China National Knowledge Infrastructure,
Database of Chinese Scientic and Technical Periodicals, China
National Knowledge Infrastructure, and Google scholar. Medical
Subject Headings (MeSH) were used as the search terms without
restriction to MeSHMajor Topic, and the search strategy was as fol-
lows: (((Beverages[Mesh]) ORCoffee[Mesh]) ORTea[Mesh]) AND
Lung Neoplasms[Mesh]. In addition, we reviewed the reference
lists of all identied relevant publications and relevant reviews.
The number of cases and participants (person-years), and RR
95%CI for each category of tea and coffee consumption were
extracted. We extracted the RR (95%CI) that reected the greatest
degree of control for potential confounders. The median or mean
tea andcoffee consumptionfor eachcategorywere assignedtoeach
corresponding RR for every study. If the upper boundary of the
highest category was not provided, we assumed that the boundary
had the same amplitude as the adjacent category. If the data was
published more than once, we included the study with the largest
participants, otherwise, the study providing the most information
was used.
A 2-stage random-effects doseresponse meta-analysis taking
into account the between-study heterogeneity was performed pro-
posed by Orsini et al. [4] to compute the trend fromthe correlated
log RR estimates across categories of green tea, black tea and coffee
consumption. Briey, a restricted cubic spline model, with 4 knots
at the 5th, 35th, 65th, and 95th percentiles [5] of the green tea,
black tea and coffee consumption levels, was estimated using gen-
eralized least square regression taking into account the correlation
within each set of published RRs [6]. Then the restricted maximum
likelihood method in a multivariate random-effects meta-analysis
[7] was used to combined the study-specic estimates. A P value
for nonlinearity and overall signicance of the curve was calcu-
lated using the method proposed by Greenland and Longnecker
[8]. All statistical analyses were performed with STATA version 12
(Stata Corporation, College Station, TX, USA). All reportedprobabili-
ties (Pvalues) weretwo-sided, withP0.05consideredstatistically
signicant.
For green tea, data from 6 publications [914] were used
including 2381 lung cancer cases. A signicantly nonlinear rela-
tionship was found of green tea consumption with risk of lung
cancer (P
for non-linearity
<0.00, P
for overall signicance
<0.00), andthe RRs
(95%CI) of lung cancer was 0.81 (0.730.89), 0.73 (0.630.84), 0.73
(0.620.85), 0.78 (0.650.90), 0.81 (0.680.95), 0.83 (0.690.99),
0.82 (0.680.99), 0.77 (0.620.94), 0.72 (0.560.87), and 0.67
(0.480.79) for 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 cups per day (Fig. 1).
Fig. 1. The doseresponse analysis between green tea consumption and risk of lung
cancer with restricted cubic splines in a multivariate random-effects doseresponse
model. The solid line and the long dash line represent the estimated relative risk and
its 95% condence interval. Short dash line represents the linear relationship.
170 Letters to the Editor / Lung Cancer 78 (2012) 167170
Fig. 2. The doseresponse analysis between coffee consumption and risk of lung
cancer with restricted cubic splines in a multivariate random-effects doseresponse
model. The solid line and the long dash line represent the estimated relative risk and
its 95% condence interval of the nonlinear relationship. Short dash line represents
the linear relationship.
For black tea, data from 7 publications [1521] were used
including 3333 lung cancer cases. No signicant association was
found of black tea with risk of lung cancer (P
for non-linearity
=0.54,
P
for overall signicance
=0.78), and the RRs (95%CI) of lung cancer
was 0.93 (0.811.07), 0.96 (0.851.08), 1.00 (0.871.14), 1.01
(0.881.17) and 1.01 (0.851.20) for 1, 2, 3, 4 and 5 cups per day.
For coffee consumption, data from 9 publications [1725]
were used including 3008 lung cancer cases. A signicantly lin-
ear relationship was found of coffee consumption with risk of lung
cancer (P
for non-linearity
=0.63, P
for overall signicance
<0.00), andthe RRs
(95%CI) of lung cancer was 1.04 (0.851.26), 1.11 (0.921.34), 1.23
(1.051.44), 1.36 (1.171.59), 1.53 (1.301.79), 1.72 (1.392.11),
and 1.95 (1.452.61) for 1, 2, 3, 4, 5, 6 and 7 cups per day (Fig. 2).
Overall, this doseresponse analysis suggesteda favorable effect
of green tea consumption on lung cancer, especially for consumers
of >7 cups per day, while no signicant association was found of
black tea consumption with lung cancer. And a linear relationship
was found between coffee consumption and increased risk of lung
caner, especially for consumers of 3 cups per day.
Conict of interest
None.
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Yaopeng Wang
Department of Thoracic Surgery, The Afliated
Hospital of Medical College of Qingdao University,
Jiangsu Road, No. 19, Qingdao 266001,
Shandong, PR China
Xuyi Yu
Department of Medicine, Center Hospital of Qingdao
City, Siliu South Road, No. 147, Qingdao 266031,
Shandong, PR China
Yili Wu
Dongfeng Zhang

Department of Epidemiology and Health Statistics,

The Medical College of Qingdao University, Dongzhou
Road, No. 38, Qingdao 266021, Shandong, PR China

Corresponding author. Tel.: +86 532 82991712.

E-mail address: zhangdf1962@yahoo.com.cn
(D. Zhang)
8 August 2012
doi:10.1016/j.lungcan.2012.08.009