Abstract

Background: Whether an association between alcohol drinking and gastric cancer risk exists is an open question. In order to provide a definite quantification of the association between alcohol drinking and gastric cancer risk, we conducted a meta-analysis of available data.

Patients and methods: We carried out a PubMed search of articles published up to June 2010 and identified 44 case–control and 15 cohort studies, including a total of 34 557 gastric cancer cases. We derived meta-analytic estimates using random-effects models, taking into account correlation between estimates. We carried out a dose–risk analysis using nonlinear random-effects meta-regression models.

Results: Compared with nondrinkers, the pooled relative risk (RR) was 1.07 [95% confidence interval (CI) 1.01–1.13] for alcohol drinkers and 1.20 (95% CI 1.01–1.44) for heavy alcohol drinkers (≥4 drinks per day). The pooled estimates were apparently higher for gastric noncardia (RR for heavy drinkers = 1.17, 95% CI 0.78–1.75) than for gastric cardia (RR = 0.99, 95% CI 0.67–1.47) adenocarcinoma. The dose–risk model estimated a RR of 0.95 (95% CI 0.91–0.99) for 10 g/day and 1.14 (95% CI 1.08–1.21) for 50 g/day.

Conclusions: This meta-analysis provides definite evidence of a lack of association between moderate alcohol drinking and gastric cancer risk. There was, however, a positive association with heavy alcohol drinking.

introduction

Whether an association between alcohol drinking and stomach cancer risk exists is an open question. In 1988, an International Agency for Research on Cancer (IARC) working group concluded that there was inadequate evidence for the carcinogenicity of alcohol on gastric cancer [1]. In 2007, in a reassessment of the carcinogenicity of alcoholic beverages, the IARC working group concluded that for stomach cancer ‘there were suggestions that alcohol consumption might be associated with an increased risk, but confounding by smoking and dietary habits could not be ruled out’ [2].

A relation between alcohol drinking and gastric cancer risk is biologically plausible. Heavy alcohol consumption could cause chronic gastritis, which could predispose to cancer [3, 4]. However, it is unclear whether any potential relation between large amounts of alcohol drinking and stomach cancer risk is real or due to residual confounding by smoking and other risk factors of gastric cancer. Moreover, it is not known whether alcohol exerts a different carcinogenic effect on different portions of the stomach, notably on the cardia.

To address these issues, we conducted a meta-analysis of studies published on alcohol consumption and the risk of stomach cancer.

materials and methods

identification of studies and data collection

We carried out a literature search, using PubMed, of all case–control and cohort studies published as original articles in English up to June 2010, using the MeSH terms ‘alcohol drinking’ or ‘alcoholic beverages’ and ‘stomach neoplasms’, following the Meta-analysis Of Observational Studies in Epidemiology guidelines [5]. Supplemental Figure S1 (available at Annals of Oncology online) provides the flowchart for the selection of articles. Three of the authors (FI, LS and IT) retrieved and assessed potentially relevant papers, and reviewed the reference list in the articles to identify additional publications of interest. When multiple reports were published on the same study, we considered in the meta-analysis only the most informative one (usually, the most recent report). We identified 87 publications, of which 27 were excluded because they did not fulfill the inclusion criteria [i.e. studies not reporting the odds ratio (OR) or relative risk (RR) and the corresponding 95% confidence intervals (CIs), or sufficient information to calculate them], and one was excluded for inconsistency of the ethanol content estimation (i.e. drinks of beverages and grams of ethanol per day were inconsistent) [6]. Thus, the present analyses were based on 59 studies, including 44 case–control [7–50] and 15 cohort [51–65] studies.

For each study, we extracted information on study design, country, number of subjects (cases, controls or cohort size), type of controls and period of enrollment for case–control studies, duration of follow-up for cohort studies, cancer site, sex distribution of the study population, variables adjusted for in the analysis, RR estimates and the corresponding CI and, when available, the number of cases and noncases or person-years for each category of alcohol consumption.

statistical analyses

The measure of interest was the RR (or the OR in case–control studies). Whenever available, we used multivariate-adjusted risk estimates; otherwise, we utilized or computed from the exposure distributions given in the papers the unadjusted RRs. When studies reported adjusted RR estimates without CIs, we computed the standard error (SE) using the SE from the unadjusted RR estimate penalized by a factor of 1.5, consistently with our companion meta-analyses on alcohol drinking and oral/pharyngeal [66] and laryngeal [67] cancers.

Since different units were used to express alcohol intake, we converted alcohol consumption categories into grams of ethanol per day as a standard measure of alcohol intake. The dose associated to each RR estimate was computed as the midpoint of each exposure category, and, for the open-ended upper category, as 1.2 times its lower bound [68]. We defined a drink as 12.5 g of ethanol. When possible, we chose nondrinkers as the reference category; however, in several studies, occasional drinkers were included in the reference category. We defined heavy alcohol drinking as drinkers of ≥4 drinks per day. If in a particular study more than one category fell in the exposure level considered, we combined the corresponding estimates using the method proposed by Hamling et al. [69]. This method was used to combine estimates using the same reference category or the same set of controls (e.g. gastric cardia versus gastric noncardia), taking into account correlation between estimates. It uses the adjusted estimates and the number of exposed and nonexposed subjects to derive a corresponding set of pseudonumbers of cases and controls/subjects at risk consistent with the reported adjusted estimates.

We generated forest plots for alcohol drinkers versus nondrinkers, overall, by cancer subsite (cardia versus noncardia) and by geographic area (Asian versus non-Asian studies). We also calculated the corresponding RR estimates of gastric cancer for heavy alcohol drinking and the RRs for alcohol drinkers versus nondrinkers in strata of selected covariates. Moreover, we computed RRs of gastric cancer based on studies reporting estimates for nonsmokers only. All the meta-analytic estimates were derived using random-effects models [70]. We assessed the heterogeneity among studies using the chi-square test [70], defining a significant heterogeneity as a P value of <0.10 and quantified the inconsistency using the I-squared statistic [71].

We carried out a dose–response analysis using a random-effects meta-regression model in a nonlinear dose–response relationship framework, providing the best-fitting two-term fractional-polynomial model [72].

We also carried out a publication bias analysis through the contour-enhanced funnel plot [73] and the Egger’s test for funnel plot asymmetry [74].

results

The main characteristics of the 59 studies [7–65] included in the meta-analysis are given in supplemental Table S1 (available at Annals of Oncology online). A total of 34 557 gastric cancer cases were included.

Figure 1 shows the RRs of gastric cancer and alcohol drinking (drinkers versus nondrinkers), overall, by anatomic subsite and by geographic area. The overall RR, based on 44 case–control and 15 cohort studies, was 1.07 (95% CI 1.01–1.13). The corresponding estimates were 1.08 (95% CI 1.00–1.18) for case–control and 1.04 (95% CI 0.97–1.11) for cohort studies (P for heterogeneity = 0.488). The summary RRs were 0.94 (95% CI 0.78–1.13) for gastric cardia and 1.07 (95% CI 0.91–1.26) for gastric noncardia (P for heterogeneity = 0.303), based on 11 (two cohorts) and 13 (three cohorts) studies, respectively. The RR for drinkers versus nondrinkers was 1.02 (95% CI 0.95–1.09) among Asian and 1.12 (95% CI 1.01–1.24) among non-Asian studies (P for heterogeneity = 0.138).

Figure 1.

Summary relative risks (RRs) of alcohol drinking (drinkers versus nondrinkers) and gastric cancer, overall (A), by anatomic subsite (B) and by geographic area (C). M, men; W, women; M + W, men and women considered together; PY, person years.

Figure 1.

Summary relative risks (RRs) of alcohol drinking (drinkers versus nondrinkers) and gastric cancer, overall (A), by anatomic subsite (B) and by geographic area (C). M, men; W, women; M + W, men and women considered together; PY, person years.

Figure 2 shows the forest plots for heavy alcohol drinking, overall, by anatomic subsite and by geographic area. The overall RR, based on 13 studies, was 1.20 (95% CI 1.01–1.44). The RR was somewhat weaker in cohort (RR = 1.12, 95% CI 0.85–1.48) than in case–control (RR = 1.22, 95% CI 0.98–1.52) studies. The estimates were 0.99 (95% CI 0.67–1.47) for gastric cardia and 1.17 (95% CI 0.78–1.75) for gastric noncardia (P for heterogeneity = 0.561), both based on five (all case–control) studies. The RR for heavy alcohol drinking was 0.90 (95% CI 0.65–1.25) among Asian and 1.39 (95% CI 1.14–1.69) among non-Asian studies (P for heterogeneity = 0.026).

Figure 2.

Summary relative risks (RRs) of heavy alcohol drinking (≥4 drinks per day) and gastric cancer, overall (A), by anatomic subsite (B) and by geographic area (C). M, men; W, women; M + W, men and women considered together.

Figure 2.

Summary relative risks (RRs) of heavy alcohol drinking (≥4 drinks per day) and gastric cancer, overall (A), by anatomic subsite (B) and by geographic area (C). M, men; W, women; M + W, men and women considered together.

Table 1 considers the association between alcohol and gastric cancer, in stratified analyses. No significant differences were found across strata of sex, geographic area or between studies with and without adjustment for smoking and fruit and vegetable consumption. Among nonsmokers, the summary RR for alcohol drinking was 1.06 (95% CI 0.96–1.17; I-squared = 0.0%, P = 0.520), based on four case–control and three cohort studies (data not shown).

Table 1.

Summary RRs of alcohol drinking (drinkers versus nondrinkers) and gastric cancer, in strata of selected covariates

 n RR (95% CI) χ12 Heterogeneity (P value) 
Total 59 1.07 (1.01–1.13)  
Sex    
    Men 31 1.07 (0.91–1.26) 0.924 (0.336) 
    Women 16 0.96 (0.83–1.12) 
Geographic area    
    Asia 26 1.02 (0.95–1.09) 2.204 (0.138) 
    Other countries 32 1.12 (1.01–1.24) 
Adjustment for smoking habit    
    Unadjusted estimates 32 1.04 (0.96–1.11) 1.336 (0.248) 
    Adjusted estimates 29 1.12 (1.01–1.24) 
Adjustment for fruit and vegetable consumption    
    Unadjusted estimates 47 1.05 (1.00–1.12) 0.904 (0.342) 
    Adjusted estimates 13 1.16 (0.95–1.41) 
 n RR (95% CI) χ12 Heterogeneity (P value) 
Total 59 1.07 (1.01–1.13)  
Sex    
    Men 31 1.07 (0.91–1.26) 0.924 (0.336) 
    Women 16 0.96 (0.83–1.12) 
Geographic area    
    Asia 26 1.02 (0.95–1.09) 2.204 (0.138) 
    Other countries 32 1.12 (1.01–1.24) 
Adjustment for smoking habit    
    Unadjusted estimates 32 1.04 (0.96–1.11) 1.336 (0.248) 
    Adjusted estimates 29 1.12 (1.01–1.24) 
Adjustment for fruit and vegetable consumption    
    Unadjusted estimates 47 1.05 (1.00–1.12) 0.904 (0.342) 
    Adjusted estimates 13 1.16 (0.95–1.41) 

RR, relative risk; CI, confidence interval.

Figure 3 shows the dose–response analysis, giving the RR function and the corresponding 95% CI for the best-fitting relationship between alcohol consumption and gastric cancer risk [i.e. ln(RR) = ln(dose) + dose1/2]. This function has a minimum at 10 g/day, and the estimated RRs are 0.95 (95% CI 0.91–0.99) for 10, 1.01 (95% CI 0.96–1.06) for 25, 1.14 (95% CI 1.08–1.21) for 50, 1.30 (95% CI 1.19–1.40) for 75, 1.45 (95% CI 1.31–1.62) for 100 and 1.62 (95% CI 1.42–1.85) for 125 grams of ethanol per day.

Figure 3.

Relative risk function and the corresponding 95% confidence interval, describing the best-fitting dose–response relationship between alcohol consumption and gastric cancer risk.

Figure 3.

Relative risk function and the corresponding 95% confidence interval, describing the best-fitting dose–response relationship between alcohol consumption and gastric cancer risk.

Supplemental Figure S2 (available at Annals of Oncology online) shows the contour-enhanced funnel plot of studies on the association between alcohol drinking and gastric cancer risk. The graph appears to be symmetrical, suggesting the absence of a publication bias. Likewise, we found no asymmetry according to the Egger’s test (P = 0.240).

discussion

In the present meta-analysis, we found no association between moderate alcohol drinking and gastric cancer risk, but a positive association with heavy alcohol consumption. Our results provide, therefore, more precise and valid estimates of risk than previously available [11, 18, 22, 33, 38, 54, 63].

We found higher RRs for gastric noncardia than for gastric cardia adenocarcinoma, where there was no indication of any excess. Likewise, for esophageal adenocarcinoma, several studies failed to find a consistent association with alcohol [75]. Moreover, in a companion meta-analysis on alcohol consumption and esophageal and gastric cardia adenocarcinoma risk, we did not find any association even at higher doses.

We also found a significant heterogeneity for heavy alcohol drinking by geographic area, suggesting no excess risk among Asian studies. This can be related to a role of aldehyde dehydrogenase (ADH) and alcohol dehydrogenase (ALDH) polymorphisms, which have been related to excess head and neck, esophageal and gastric cancer risk in Japan [76–78]. In fact, subjects with the ADH and ALDH mutant alleles cannot be heavy drinkers, and this reduces the prevalence of heavy drinking in Asian population [76–78].

Our results are in accordance with those of a Chinese cohort study published in September 2010, and thus not included in the present meta-analysis, based on 18 244 men followed for 20 years and 391 incident gastric cancer cases, which found, compared with nondrinkers, hazard ratios of 1.03 (95% CI 0.83–1.26) for drinkers, 0.94 (95% CI 0.76–1.18) for moderate (<4 drinks per day) and 1.46 (95% CI 1.05–2.04) for heavy drinkers (≥4 drinks per day) [79].

Considering drinkers versus nondrinkers, we found no significant difference across strata of any selected covariates, including adjustment for smoking and fruit and vegetable consumption, indicating a lack of appreciable confounding effect due to these factors. Moreover, among nonsmokers, we found a RR similar to the overall estimate. However, a confounding effect due to dietary habits cannot be ruled out. In fact, heavy alcohol drinking is commonly associated with poor nutrition and this could increase the risk in heavy drinkers [80–82]. The dose–risk relation had a minimum at 10 g/day. This may be due to a favorable role of moderate alcohol consumption on Helicobacter pylori gastric infection, or, most likely, to the observation that moderate drinkers tend to have more favorable dietary patterns than both nondrinkers and heavy drinkers in several populations [80–82].

H. pylori is a major risk factor for gastric cancer [83, 84] and is present in most (if not all) cases. Adequate adjustment for H. pylori is therefore impossible. Thus, there was no study reporting RR for alcohol consumption and gastric cancer adjusted for H. pylori infection. Only one study [38] reported gastric cancer risk associated with vodka consumption among H. pylori-positive and H. pylori-negative subjects. Compared with H. pylori-negative subjects, H. pylori-positive subjects showed a slightly higher OR for vodka drinking (2.3 versus 2.0), in the absence, however, of a significant interaction between vodka and H. pylori infection (P = 0.51) [38].

With reference to possible limitations, in this meta-analysis there was no significant heterogeneity in several estimates. Furthermore, the use of the random-effects model to derive summary estimates allowed to account for heterogeneity among studies [70]. Moreover, the contour-enhanced funnel plot and the Egger’s test for funnel plot asymmetry did not support the presence of major publication bias, providing further indication of the robustness of our results. A more general issue is that alcohol drinking, and particularly heavy drinking, is underreported in observational studies. However, studies investigating reproducibility and validity of self-reported alcohol drinking in various populations found satisfactory correlation coefficients i.e. between 0.61 and 0.99 [85–90]. Moreover, estimates from cohort studies, which are less subject to bias (e.g. the differential reporting of alcohol consumption), were lower, but not significantly different, compared with case–control ones.

Thus, the present comprehensive meta-analysis provides evidence of a lack of appreciable association between moderate alcohol drinking and gastric cancer risk. There was, however, a positive association with heavy alcohol drinking, particularly for noncardia adenocarcinomas.

funding

This work was conducted with the contribution of the Italian Association for Cancer Research (AIRC), project No. 10068 and 10258 My First AIRC Grant (MFAG), and the Flight Attendant Medical Research Institute (FAMRI) Center of Excellence Award, project No. 052460_CoE. IT was supported by a fellowship from the Italian Foundation for Cancer Research (FIRC).

disclosure

The authors declare no conflict of interest.

The authors thank I. Garimoldi for editorial assistance.

References

1.
IARC Working Group
Alcohol drinking
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans
 , 
1988
, vol. 
Vol. 44
 
Lyon, France
IARC Press
2.
Baan
R
Straif
K
Grosse
Y
, et al.  . 
Carcinogenicity of alcoholic beverages
Lancet Oncol
 , 
2007
, vol. 
8
 (pg. 
292
-
293
)
3.
Correa
P
A human model of gastric carcinogenesis
Cancer Res
 , 
1988
, vol. 
48
 (pg. 
3554
-
3560
)
4.
Franceschi
S
La Vecchia
C
Alcohol and the risk of cancers of the stomach and colon-rectum
Dig Dis
 , 
1994
, vol. 
12
 (pg. 
276
-
289
)
5.
Stroup
DF
Berlin
JA
Morton
SC
, et al.  . 
Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group
JAMA
 , 
2000
, vol. 
283
 (pg. 
2008
-
2012
)
6.
Lopez-Carrillo
L
Lopez-Cervantes
M
Ramirez-Espitia
A
, et al.  . 
Alcohol consumption and gastric cancer in Mexico
Cad Saude Publica
 , 
1998
, vol. 
14
 
Suppl 3
(pg. 
25
-
32
)
7.
Wynder
EL
Kmet
J
Dungal
N
Segi
M
An epidemiological investigation of gastric cancer
Cancer
 , 
1963
, vol. 
16
 (pg. 
1461
-
1496
)
8.
Higginson
J
Etiological factors in gastrointestinal cancer in man
J Natl Cancer Inst
 , 
1966
, vol. 
37
 (pg. 
527
-
545
)
9.
Graham
S
Schotz
W
Martino
P
Alimentary factors in the epidemiology of gastric cancer
Cancer
 , 
1972
, vol. 
30
 (pg. 
927
-
938
)
10.
Haenszel
W
Kurihara
M
Segi
M
Lee
RK
Stomach cancer among Japanese in Hawaii
J Natl Cancer Inst
 , 
1972
, vol. 
49
 (pg. 
969
-
988
)
11.
Hoey
J
Montvernay
C
Lambert
R
Wine and tobacco: risk factors for gastric cancer in France
Am J Epidemiol
 , 
1981
, vol. 
113
 (pg. 
668
-
674
)
12.
Tuyns
AJ
Pequignot
G
Gignoux
M
Valla
A
Cancers of the digestive tract, alcohol and tobacco
Int J Cancer
 , 
1982
, vol. 
30
 (pg. 
9
-
11
)
13.
Correa
P
Fontham
E
Pickle
LW
, et al.  . 
Dietary determinants of gastric cancer in South Louisiana inhabitants
J Natl Cancer Inst
 , 
1985
, vol. 
75
 (pg. 
645
-
654
)
14.
Hu
JF
Zhang
SF
Jia
EM
, et al.  . 
Diet and cancer of the stomach: a case-control study in China
Int J Cancer
 , 
1988
, vol. 
41
 (pg. 
331
-
335
)
15.
You
WC
Blot
WJ
Chang
YS
, et al.  . 
Diet and high risk of stomach cancer in Shandong, China
Cancer Res
 , 
1988
, vol. 
48
 (pg. 
3518
-
3523
)
16.
Unakami
M
Hara
M
Fukuchi
S
Akiyama
H
Cancer of the gastric cardia and the habit of smoking
Acta Pathol Jpn
 , 
1989
, vol. 
39
 (pg. 
420
-
424
)
17.
Buiatti
E
Palli
D
Decarli
A
, et al.  . 
A case-control study of gastric cancer and diet in Italy: II. Association with nutrients
Int J Cancer
 , 
1990
, vol. 
45
 (pg. 
896
-
901
)
18.
De Stefani
E
Correa
P
Fierro
L
, et al.  . 
Alcohol drinking and tobacco smoking in gastric cancer. A case-control study
Rev Epidemiol Sante Publique
 , 
1990
, vol. 
38
 (pg. 
297
-
307
)
19.
Demirer
T
Icli
F
Uzunalimoglu
O
Kucuk
O
Diet and stomach cancer incidence. A case-control study in Turkey
Cancer
 , 
1990
, vol. 
65
 (pg. 
2344
-
2348
)
20.
Kato
I
Tominaga
S
Ito
Y
, et al.  . 
A comparative case-control analysis of stomach cancer and atrophic gastritis
Cancer Res
 , 
1990
, vol. 
50
 (pg. 
6559
-
6564
)
21.
Lee
HH
Wu
HY
Chuang
YC
, et al.  . 
Epidemiologic characteristics and multiple risk factors of stomach cancer in Taiwan
Anticancer Res
 , 
1990
, vol. 
10
 (pg. 
875
-
881
)
22.
Wu-Williams
AH
Yu
MC
Mack
TM
Life-style, workplace, and stomach cancer by subsite in young men of Los Angeles County
Cancer Res
 , 
1990
, vol. 
50
 (pg. 
2569
-
2576
)
23.
Tominaga
K
Koyama
Y
Sasagawa
M
, et al.  . 
A case-control study of stomach cancer and its genesis in relation to alcohol consumption, smoking, and familial cancer history
Jpn J Cancer Res
 , 
1991
, vol. 
82
 (pg. 
974
-
979
)
24.
Yu
GP
Hsieh
CC
Risk factors for stomach cancer: a population-based case-control study in Shanghai
Cancer Causes Control
 , 
1991
, vol. 
2
 (pg. 
169
-
174
)
25.
Agudo
A
Gonzalez
CA
Marcos
G
, et al.  . 
Consumption of alcohol, coffee, and tobacco, and gastric cancer in Spain
Cancer Causes Control
 , 
1992
, vol. 
3
 (pg. 
137
-
143
)
26.
Hoshiyama
Y
Sasaba
T
A case-control study of stomach cancer and its relation to diet, cigarettes, and alcohol consumption in Saitama Prefecture, Japan
Cancer Causes Control
 , 
1992
, vol. 
3
 (pg. 
441
-
448
)
27.
D'Avanzo
B
La Vecchia
C
Franceschi
S
Alcohol consumption and the risk of gastric cancer
Nutr Cancer
 , 
1994
, vol. 
22
 (pg. 
57
-
64
)
28.
Inoue
M
Tajima
K
Hirose
K
, et al.  . 
Life-style and subsite of gastric cancer–joint effect of smoking and drinking habits
Int J Cancer
 , 
1994
, vol. 
56
 (pg. 
494
-
499
)
29.
Gajalakshmi
CK
Shanta
V
Lifestyle and risk of stomach cancer: a hospital-based case-control study
Int J Epidemiol
 , 
1996
, vol. 
25
 (pg. 
1146
-
1153
)
30.
Ji
BT
Chow
WH
Yang
G
, et al.  . 
The influence of cigarette smoking, alcohol, and green tea consumption on the risk of carcinoma of the cardia and distal stomach in Shanghai, China
Cancer
 , 
1996
, vol. 
77
 (pg. 
2449
-
2457
)
31.
Murata
M
Takayama
K
Choi
BC
Pak
AW
A nested case-control study on alcohol drinking, tobacco smoking, and cancer
Cancer Detect Prev
 , 
1996
, vol. 
20
 (pg. 
557
-
565
)
32.
Zhang
ZF
Kurtz
RC
Sun
M
, et al.  . 
Adenocarcinomas of the esophagus and gastric cardia: medical conditions, tobacco, alcohol, and socioeconomic factors
Cancer Epidemiol Biomarkers Prev
 , 
1996
, vol. 
5
 (pg. 
761
-
768
)
33.
De Stefani
E
Boffetta
P
Carzoglio
J
, et al.  . 
Tobacco smoking and alcohol drinking as risk factors for stomach cancer: a case-control study in Uruguay
Cancer Causes Control
 , 
1998
, vol. 
9
 (pg. 
321
-
329
)
34.
Chow
WH
Swanson
CA
Lissowska
J
, et al.  . 
Risk of stomach cancer in relation to consumption of cigarettes, alcohol, tea and coffee in Warsaw, Poland
Int J Cancer
 , 
1999
, vol. 
81
 (pg. 
871
-
876
)
35.
Ye
W
Ekstrom
AM
Hansson
LE
, et al.  . 
Tobacco, alcohol and the risk of gastric cancer by sub-site and histologic type
Int J Cancer
 , 
1999
, vol. 
83
 (pg. 
223
-
229
)
36.
Chen
MJ
Chiou
YY
Wu
DC
Wu
SL
Lifestyle habits and gastric cancer in a hospital-based case-control study in Taiwan
Am J Gastroenterol
 , 
2000
, vol. 
95
 (pg. 
3242
-
3249
)
37.
Mathew
A
Gangadharan
P
Varghese
C
Nair
MK
Diet and stomach cancer: a case-control study in South India
Eur J Cancer Prev
 , 
2000
, vol. 
9
 (pg. 
89
-
97
)
38.
Zaridze
D
Borisova
E
Maximovitch
D
Chkhikvadze
V
Alcohol consumption, smoking and risk of gastric cancer: case-control study from Moscow, Russia
Cancer Causes Control
 , 
2000
, vol. 
11
 (pg. 
363
-
371
)
39.
Wu
AH
Wan
P
Bernstein
L
A multiethnic population-based study of smoking, alcohol and body size and risk of adenocarcinomas of the stomach and esophagus (United States)
Cancer Causes Control
 , 
2001
, vol. 
12
 (pg. 
721
-
732
)
40.
Hamada
GS
Kowalski
LP
Nishimoto
IN
, et al.  . 
Risk factors for stomach cancer in Brazil (II): a case-control study among Japanese Brazilians in Sao Paulo
Jpn J Clin Oncol
 , 
2002
, vol. 
32
 (pg. 
284
-
290
)
41.
Nishimoto
IN
Hamada
GS
Kowalski
LP
, et al.  . 
Risk factors for stomach cancer in Brazil (I): a case-control study among non-Japanese Brazilians in Sao Paulo
Jpn J Clin Oncol
 , 
2002
, vol. 
32
 (pg. 
277
-
283
)
42.
Rao
DN
Ganesh
B
Dinshaw
KA
Mohandas
KM
A case-control study of stomach cancer in Mumbai, India
Int J Cancer
 , 
2002
, vol. 
99
 (pg. 
727
-
731
)
43.
Nomura
AM
Hankin
JH
Kolonel
LN
, et al.  . 
Case-control study of diet and other risk factors for gastric cancer in Hawaii (United States)
Cancer Causes Control
 , 
2003
, vol. 
14
 (pg. 
547
-
558
)
44.
Lindblad
M
Rodriguez
LA
Lagergren
J
Body mass, tobacco and alcohol and risk of esophageal, gastric cardia, and gastric non-cardia adenocarcinoma among men and women in a nested case-control study
Cancer Causes Control
 , 
2005
, vol. 
16
 (pg. 
285
-
294
)
45.
Boccia
S
Sayed-Tabatabaei
FA
Persiani
R
, et al.  . 
Polymorphisms in metabolic genes, their combination and interaction with tobacco smoke and alcohol consumption and risk of gastric cancer: a case-control study in an Italian population
BMC Cancer
 , 
2007
, vol. 
7
 pg. 
206
 
46.
Lucenteforte
E
Scita
V
Bosetti
C
, et al.  . 
Food groups and alcoholic beverages and the risk of stomach cancer: a case-control study in Italy
Nutr Cancer
 , 
2008
, vol. 
60
 (pg. 
577
-
584
)
47.
Persson
C
Sasazuki
S
Inoue
M
, et al.  . 
Plasma levels of carotenoids, retinol and tocopherol and the risk of gastric cancer in Japan: a nested case-control study
Carcinogenesis
 , 
2008
, vol. 
29
 (pg. 
1042
-
1048
)
48.
Suwanrungruang
K
Sriamporn
S
Wiangnon
S
, et al.  . 
Lifestyle-related risk factors for stomach cancer in northeast Thailand
Asian Pac J Cancer Prev
 , 
2008
, vol. 
9
 (pg. 
71
-
75
)
49.
Zhang
P
Di
JZ
Zhu
ZZ
, et al.  . 
Association of transforming growth factor-beta 1 polymorphisms with genetic susceptibility to TNM stage I or II gastric cancer
Jpn J Clin Oncol
 , 
2008
, vol. 
38
 (pg. 
861
-
866
)
50.
Nguyen
TV
Janssen
MJ
van Oijen
MG
, et al.  . 
Genetic polymorphisms in GSTA1, GSTP1, GSTT1, and GSTM1 and gastric cancer risk in a Vietnamese population
Oncol Res
 , 
2010
, vol. 
18
 (pg. 
349
-
355
)
51.
Gordon
T
Kannel
WB
Drinking and mortality. The Framingham Study
Am J Epidemiol
 , 
1984
, vol. 
120
 (pg. 
97
-
107
)
52.
Kono
S
Ikeda
M
Tokudome
S
, et al.  . 
Cigarette smoking, alcohol and cancer mortality: a cohort study of male Japanese physicians
Jpn J Cancer Res
 , 
1987
, vol. 
78
 (pg. 
1323
-
1328
)
53.
Stemmermann
GN
Nomura
AM
Chyou
PH
Yoshizawa
C
Prospective study of alcohol intake and large bowel cancer
Dig Dis Sci
 , 
1990
, vol. 
35
 (pg. 
1414
-
1420
)
54.
Kato
I
Tominaga
S
Matsumoto
K
A prospective study of stomach cancer among a rural Japanese population: a 6-year survey
Jpn J Cancer Res
 , 
1992
, vol. 
83
 (pg. 
568
-
575
)
55.
Galanis
DJ
Kolonel
LN
Lee
J
Nomura
A
Intakes of selected foods and beverages and the incidence of gastric cancer among the Japanese residents of Hawaii: a prospective study
Int J Epidemiol
 , 
1998
, vol. 
27
 (pg. 
173
-
180
)
56.
Fujino
Y
Tamakoshi
A
Ohno
Y
, et al.  . 
Prospective study of educational background and stomach cancer in Japan
Prev Med
 , 
2002
, vol. 
35
 (pg. 
121
-
127
)
57.
Sasazuki
S
Sasaki
S
Tsugane
S
Cigarette smoking, alcohol consumption and subsequent gastric cancer risk by subsite and histologic type
Int J Cancer
 , 
2002
, vol. 
101
 (pg. 
560
-
566
)
58.
Barstad
B
Sorensen
TI
Tjonneland
A
, et al.  . 
Intake of wine, beer and spirits and risk of gastric cancer
Eur J Cancer Prev
 , 
2005
, vol. 
14
 (pg. 
239
-
243
)
59.
Nakaya
N
Tsubono
Y
Kuriyama
S
, et al.  . 
Alcohol consumption and the risk of cancer in Japanese men: the Miyagi cohort study
Eur J Cancer Prev
 , 
2005
, vol. 
14
 (pg. 
169
-
174
)
60.
Freedman
ND
Abnet
CC
Leitzmann
MF
, et al.  . 
A prospective study of tobacco, alcohol, and the risk of esophageal and gastric cancer subtypes
Am J Epidemiol
 , 
2007
, vol. 
165
 (pg. 
1424
-
1433
)
61.
Larsson
SC
Giovannucci
E
Wolk
A
Alcoholic beverage consumption and gastric cancer risk: a prospective population-based study in women
Int J Cancer
 , 
2007
, vol. 
120
 (pg. 
373
-
377
)
62.
Sjodahl
K
Lu
Y
Nilsen
TI
, et al.  . 
Smoking and alcohol drinking in relation to risk of gastric cancer: a population-based, prospective cohort study
Int J Cancer
 , 
2007
, vol. 
120
 (pg. 
128
-
132
)
63.
Sung
NY
Choi
KS
Park
EC
, et al.  . 
Smoking, alcohol and gastric cancer risk in Korean men: the National Health Insurance Corporation Study
Br J Cancer
 , 
2007
, vol. 
97
 (pg. 
700
-
704
)
64.
Kim
J
Park
S
Nam
BH
Gastric cancer and salt preference: a population-based cohort study in Korea
Am J Clin Nutr
 , 
2010
, vol. 
91
 (pg. 
1289
-
1293
)
65.
Steevens
J
Schouten
LJ
Goldbohm
RA
van den Brandt
PA
Alcohol consumption, cigarette smoking and risk of subtypes of oesophageal and gastric cancer: a prospective cohort study
Gut
 , 
2010
, vol. 
59
 (pg. 
39
-
48
)
66.
Tramacere
I
Negri
E
Bagnardi
V
, et al.  . 
A meta-analysis of alcohol drinking and oral and pharyngeal cancers. Part 1: overall results and dose-risk relation
Oral Oncol
 , 
2010
, vol. 
46
 (pg. 
497
-
503
)
67.
Islami
F
Tramacere
I
Rota
M
, et al.  . 
Alcohol drinking and laryngeal cancer: overall and dose-risk relation—a systematic review and meta-analysis
Oral Oncol
  
[Epub ahead of print
 
]
68.
Berlin
JA
Longnecker
MP
Greenland
S
Meta-analysis of epidemiologic dose-response data
Epidemiology
 , 
1993
, vol. 
4
 (pg. 
218
-
228
)
69.
Hamling
J
Lee
P
Weitkunat
R
Ambuhl
M
Facilitating meta-analyses by deriving relative effect and precision estimates for alternative comparisons from a set of estimates presented by exposure level or disease category
Stat Med
 , 
2008
, vol. 
27
 (pg. 
954
-
970
)
70.
Greenland
S
Quantitative methods in the review of epidemiologic literature
Epidemiol Rev
 , 
1987
, vol. 
9
 (pg. 
1
-
30
)
71.
Higgins
JP
Thompson
SG
Deeks
JJ
Altman
DG
Measuring inconsistency in meta-analyses
BMJ
 , 
2003
, vol. 
327
 (pg. 
557
-
560
)
72.
Rota
M
Bellocco
R
Scotti
L
, et al.  . 
Random-effects meta-regression models for studying nonlinear dose-response relationship, with an application to alcohol and esophageal squamous cell carcinoma
Stat Med
 , 
2010
, vol. 
29
 (pg. 
2679
-
2687
)
73.
Peters
JL
Sutton
AJ
Jones
DR
, et al.  . 
Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry
J Clin Epidemiol
 , 
2008
, vol. 
61
 (pg. 
991
-
996
)
74.
Egger
M
Davey Smith
G
Schneider
M
Minder
C
Bias in meta-analysis detected by a simple, graphical test
BMJ
 , 
1997
, vol. 
315
 (pg. 
629
-
634
)
75.
Pera
M
Manterola
C
Vidal
O
Grande
L
Epidemiology of esophageal adenocarcinoma
J Surg Oncol
 , 
2005
, vol. 
92
 (pg. 
151
-
159
)
76.
Hiraki
A
Matsuo
K
Wakai
K
, et al.  . 
Gene-gene and gene-environment interactions between alcohol drinking habit and polymorphisms in alcohol-metabolizing enzyme genes and the risk of head and neck cancer in Japan
Cancer Sci
 , 
2007
, vol. 
98
 (pg. 
1087
-
1091
)
77.
Matsuo
K
Hamajima
N
Shinoda
M
, et al.  . 
Gene-environment interaction between an aldehyde dehydrogenase-2 (ALDH2) polymorphism and alcohol consumption for the risk of esophageal cancer
Carcinogenesis
 , 
2001
, vol. 
22
 (pg. 
913
-
916
)
78.
Yokoyama
A
Muramatsu
T
Omori
T
, et al.  . 
Alcohol and aldehyde dehydrogenase gene polymorphisms and oropharyngolaryngeal, esophageal and stomach cancers in Japanese alcoholics
Carcinogenesis
 , 
2001
, vol. 
22
 (pg. 
433
-
439
)
79.
Moy
KA
Fan
Y
Wang
R
, et al.  . 
Alcohol and tobacco use in relation to gastric cancer: a prospective study of men in Shanghai, China
Cancer Epidemiol Biomarkers Prev
 , 
2010
, vol. 
19
 (pg. 
2287
-
2297
)
80.
D'Avanzo
B
La Vecchia
C
Braga
C
, et al.  . 
Nutrient intake according to education, smoking, and alcohol in Italian women
Nutr Cancer
 , 
1997
, vol. 
28
 (pg. 
46
-
51
)
81.
Klatsky
AL
Diet, alcohol, and health: a story of connections, confounders, and cofactors
Am J Clin Nutr
 , 
2001
, vol. 
74
 (pg. 
279
-
280
)
82.
La Vecchia
C
Negri
E
Franceschi
S
, et al.  . 
Differences in dietary intake with smoking, alcohol, and education
Nutr Cancer
 , 
1992
, vol. 
17
 (pg. 
297
-
304
)
83.
Munoz
N
Franceschi
S
Epidemiology of gastric cancer and perspectives for prevention
Salud Publica Mex
 , 
1997
, vol. 
39
 (pg. 
318
-
330
)
84.
Roder
DM
The epidemiology of gastric cancer
Gastric Cancer
 , 
2002
, vol. 
5
 
Suppl 1
(pg. 
5
-
11
)
85.
D'Avanzo
B
La Vecchia
C
Katsouyanni
K
, et al.  . 
Reliability of information on cigarette smoking and beverage consumption provided by hospital controls
Epidemiology
 , 
1996
, vol. 
7
 (pg. 
312
-
315
)
86.
Ferraroni
M
Decarli
A
Franceschi
S
, et al.  . 
Validity and reproducibility of alcohol consumption in Italy
Int J Epidemiol
 , 
1996
, vol. 
25
 (pg. 
775
-
782
)
87.
Flagg
EW
Coates
RJ
Calle
EE
, et al.  . 
Validation of the American Cancer Society Cancer Prevention study II nutrition survey cohort food frequency questionnaire
Epidemiology
 , 
2000
, vol. 
11
 (pg. 
462
-
468
)
88.
Giovannucci
E
Colditz
G
Stampfer
MJ
, et al.  . 
The assessment of alcohol consumption by a simple self-administered questionnaire
Am J Epidemiol
 , 
1991
, vol. 
133
 (pg. 
810
-
817
)
89.
Horn-Ross
PL
Lee
VS
Collins
CN
, et al.  . 
Dietary assessment in the California Teachers Study: reproducibility and validity
Cancer Causes Control
 , 
2008
, vol. 
19
 (pg. 
595
-
603
)
90.
Munger
RG
Folsom
AR
Kushi
LH
, et al.  . 
Dietary assessment of older Iowa women with a food frequency questionnaire: nutrient intake, reproducibility, and comparison with 24-hour dietary recall interviews
Am J Epidemiol
 , 
1992
, vol. 
136
 (pg. 
192
-
200
)