This article was downloaded by: [George Washington University] On: 07 February 2015, At: 20:37 Publisher: Routledge Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Nutrition and Cancer Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/hnuc20
Consumption of Tea and Risk for Pancreatic Cancer: A Meta-Analysis of Published Epidemiological Studies a
b
a
a
Bing Chang , Lixuan Sang , Ying Wang , Jing Tong & Bing-Yuan Wang
a
a
Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China b
Department of Cadre Ward, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China Published online: 10 Sep 2014.
Click for updates To cite this article: Bing Chang, Lixuan Sang, Ying Wang, Jing Tong & Bing-Yuan Wang (2014) Consumption of Tea and Risk for Pancreatic Cancer: A Meta-Analysis of Published Epidemiological Studies, Nutrition and Cancer, 66:7, 1109-1123, DOI: 10.1080/01635581.2014.951730 To link to this article: http://dx.doi.org/10.1080/01635581.2014.951730
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Nutrition and Cancer, 66(7), 1109–1123 Copyright Ó 2014, Taylor & Francis Group, LLC ISSN: 0163-5581 print / 1532-7914 online DOI: 10.1080/01635581.2014.951730
Consumption of Tea and Risk for Pancreatic Cancer: A Meta-Analysis of Published Epidemiological Studies Bing Chang Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
Lixuan Sang
Downloaded by [George Washington University] at 20:37 07 February 2015
Department of Cadre Ward, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
Ying Wang, Jing Tong, and Bing-Yuan Wang Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
Epidemiologic studies on the relationship between tea consumption and pancreatic cancer are inconsistent. Therefore, we conducted a systematic search of databases and performed a meta-analysis to analyze the association between tea consumption and risk of pancreatic cancer. We searched Medline, EMBASE, ISI Web of Science, and the Cochrane library for studies of tea consumption and pancreatic cancer published up to December 2012. Subgroup analysis was conducted by study type, study region, sex, type of tea, without or with adjustment for smoking, and body mass index. We performed a meta-analysis of 8 casecontrol studies and 6 cohort studies. For pancreatic cancer, the summary odds ratio (OR) for highest vs. lowest was 0.95 (95% confidence interval (CI), 0.84–1.08). The summary OR for moderate vs. lowest was 1.07 (95% CI, 0.86–1.35). The summary OR for ever vs. lowest was 1.00 (95% CI, 0.86–1.16). The results of this meta-analysis suggested tea consumption is not related to pancreatic cancer risk, even at high doses. Because of the small number of studies, further prospective studies are needed.
BACKGROUND Pancreatic cancer is a common form of malignancy in the digestive system, usually with poor prognosis and high mortality. The World Health Organization Cancer Research Center estimates that 277,000 cases of pancreatic cancer are newly diagnosed each year worldwide (1). It is the 13th most common form of malignant tumor and the incidence rate is slightly higher in males than females. Over 60% of pancreatic cancers Submitted 6 June 2013; accepted in final form 12 June 2013. Address correspondence to Bing-Yuan Wang, Department of Cadre Ward, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China. E-mail: [email protected] Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/hnuc.
occur in developed countries. About 266,000 people die of pancreatic cancer each year worldwide, and the ratio between mortality and incidence rate is about 0.96 (1). The higher incidence of pancreatic cancer is in Japan where it reaches 16.9/ 100,000 (2). Worldwide the incidence of pancreatic cancer is gradually increasing along with prolonged lifespans. The diagnosis of pancreatic cancer is more difficult than other tumors of the digestive system because the pancreas is a retroperitoneal organ. This disease is usually at a late stage at diagnosis because of a lack of effective screening measures. Data from the National Cancer Institute show that tumors of only 8% of patients with pancreatic cancer are primary tumors at diagnosis and the 5-yr relative survival rate is 21.5% in these patients; 27% of patients have lymph node metastases at diagnosis and the 5-yr survival rate is 8.6%; and 53% of patients have distant metastases at diagnosis and the 5-yr survival rate is 1.8% (3). The low survival rate of pancreatic cancer is mainly due to its occult growth, with rapidly progressing growth stage, low surgical cure rate, and lack of effective treatment measures. The trend of different incidence rates and morbidity times worldwide suggests that environmental and genetic factors play important roles in the pathogenesis of pancreatic cancer. The treatment and survival time of patients have not been improved in past decades. Therefore, the prevention of pancreatic cancer is very important. It is generally agreed that many of the chemoprevention effects of tea are mediated by catechins. The major catechins in tea are epigallocatechin-3-gallate (EGCG), several studies have tried to investigate the relationship between EGCG and pancreatic cancer. Kim et al. indicates that EGCG inhibits invasion by inducing the expression of Raf kinase inhibitor 1109
1110
B. CHANG ET AL.
Downloaded by [George Washington University] at 20:37 07 February 2015
protein in AsPC‑1 human pancreatic adenocarcinoma cells through the modulation of histone deacetylase activity (4).The exact causes of pancreatic cancer and the natural history of occurrence are not very clear. However, many studies have shown that occurrence of pancreatic cancer is closely related to dietary factors. Although many epidemiological studies focus on the relationship between tea and pancreatic cancer, the data are inconclusive. Studies on the relationship between tea and pancreatic cancer from different countries have been reported since the 1990s, but meta-analysis is relatively rare. Therefore, we conducted a meta-analysis of all published studies to summarize the relationship between tea consumption and pancreatic cancer.
MATERIALS AND METHODS Literature Search Strategy We searched Medline (via PubMed; National Library of Medicine), EMBASE (Elsevier, Amsterdam, the Netherlands), ISI Web of Science (Institute for Scientific Information, Philadelphia, Pennsylvania), and the Cochrane library (Wiley, Chichester, UK) for studies published up to December 2012. Key words searched were as follows: (tea OR catechin OR beverages OR diet OR drinking OR lifestyle) AND pancreatic AND (cancer OR tumor OR neoplasm OR carcinoma) AND (risk). In addition, we also performed a manual search of reference cited in the published reviews. We restricted the search to papers published in English.
Inclusion and Exclusion Criteria The inclusion criteria were case-control or cohort study; data on the frequency of tea consumption; primary outcome defined as pancreatic cancer or pancreatic carcinoma; and relative risks (RRs) estimates, odds ratios (ORs), or hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs). Exclusion criteria included duplicate reports and insufficient data about tea consumption.
Data Extraction The following data were collected from each publication: the name of the first author, year of publication, the country where the study was conducted, study design, study population demographics, study period, sample size, type of outcome, consumption of coffee, number of exposed cases, the RRs or ORs or HRs and their 95% CIs, and covariates adjusted in the analysis. All data were extracted independently by 3 reviewers, and any disagreement was resolved by discussion among them. If results were published more than once, the results from the most recent one were selected. Because pancreatic cancer is rare, the OR was assumed to be the same as RR and HR, and all results are reported as OR for simplicity.
Statistical Analysis and Synthesis We quantified the relationship between tea consumption and pancreatic cancer risk by use of the DerSimonian and Laird (5) random effects model. We assessed the risk of pancreatic cancer for highest/moderate/ever vs. lowest consumption levels of tea. Because various sources of heterogeneity may exist owing to a variety of factors, we carried out subgroup analysis to investigate the influence of study design, study region, sex, type of tea, smoking, and body mass index (BMI). To estimate summary OR for various levels of tea consumption, we calculated the study-specific estimates for tea consumption (Table 1). We quantified the extent of heterogeneity using Q and Higgins I2 (5,6). A significant heterogeneity was defined as a P value < 0.10 or I2 > 50%. To investigate potential heterogeneity of among studies, subgroup analyses were conducted. Publication bias was assessed through visual inspection of funnel plot, Begger’s (7) and Egger’s tests (8). P < 0.05 for Begg’s or Egger’s tests was considered to be representative of a publication bias. All statistical analyses were performed with STATA (version 11.0; StataCorp, College Station, TX).
RESULTS Study Characteristics We identified 714 relevant articles on titles and abstracts from the meta-analysis shown in Fig. 1. We identified 14 articles on the relationship between tea consumption and the incidence of pancreatic cancer were published. However, 2 articles were excluded (9,10) because they did not provided risk ratios or 95% CIs. The remaining 12 articles are shown in Table 2 (11–22) (including a total of 3522 cases). Six of these were cohort studies (Michaud et al. included 2 cohort studies) (16–20), and 7 of these were case-control studies (Mizuno et al. included green tea and black tea were considered one study) (11–15,21,22). Of the selected studies, 3 were conducted in Europe (11,13,21), 3in the United States (12,17), and 7 in Asia (14–16,18–20,22). The estimated ORs of pancreatic cancer for highest versus lowest tea consumption are presented in Table 2.
Highest vs. Lowest Tea Consumption A meta-analysis of risk estimates of the incidence of pancreatic cancer for the highest compared with the lowest tea consumption category (Table 3). The summary OR was 0.95 (95% CI, 0.84–1.08). There was no statistically significant heterogeneity across studies (Q D 22.76, P D 0.045, I2 D 42.9%) (Fig. 2). No publication bias was observed from either visualization of the funnel plot, Begger’s test (P D 0.913) or Egger’s test (P D 0.673) (Fig. 3).
CONSUMPTION OF TEA AND RISK FOR PANCREATIC CANCER
714 relevant articles were identified on titles and abstracts 622 articles were excluded based on screening of titles or abstracts because they were reviews, ecological
Downloaded by [George Washington University] at 20:37 07 February 2015
studies, or laboratory studies
92 articles considered 78 design was incorrect or did not provide sufficient
1111
4.00, P D 0.135, I2 D 50%) for studies in Europe, and 0.97 (95% CI, 0.68–1.39; Q D 0.91, P D 0.64, I2 D 0%) for studies in the United States. When stratified analysis was conducted by type of tea, the OR was 0.97 (95% CI, 0.81–1.15; Q D 4.91, P D 0.427, I2 D 0%) for studies in tea, 0.96 (95% CI, 0.79–1.16; Q D 16.59, P D 0.011, I2 D 63.8%) for studies in green tea, and 0.53 (95% CI, 0.19-1.49) for study in black tea. Stratification analysis was conducted without or with adjustment for smoking. The OR was 0.98 (95% CI, 0.82– 1.07; Q D 15.63, P D 0.111, I2 D 36%) for no adjustment for smoking studies and 1.15 (95% CI, 0.74–1.79; Q D 6.37, P D 0.041, I2 D 68.6%) for the after adjustment for smoking studies. Stratification analysis was conducted without or with adjustment for BMI. The OR was 0.89 (95% CI, 0.67–1.18; Q D 18.01, P D 0.003, I2 D 72.2%) for no adjustment for BMI studies and 0.97 (95% CI, 0.84–1.12; Q D 4.44, P D 0.728, I2 D 0.00%) for after adjustment for BMI studies.
information
14 articles were selected for meta-analysis
2 articles were excluded because the articles did not provide risk ratios or 95% CIs and one article was published
12 articles (13 studies) were in Japanese selected for meta-analysis FIG. 1. Flowchart for search and selection of studies in the meta-analysis.
We assessed associations separately for study type, sex, study region, type of tea, and whether or not adjust smoking and BMI. The OR was 0.89 (95% CI, 0.76–1.04; Q D 18.61, P D 0.009, I2 D 62.4%) for case-control studies and 1.09 (95% CI, 0.88–1.35; Q D 1.99, P D 0.85, I2 D 0.0%) for the cohort studies. In a subgroup analysis conducted by sex, the OR was 1.01 (95% CI, 0.74–1.37; Q D 7.31, P D 0.199, I2 D 31.6%) for studies in males, 0.85 (95% CI, 0.50–1.43; Q D 14.94, P D 0.011, I2 D 66.5%) for studies in females, and 0.94 (95% CI, 0.71–1.25; Q D 22.7, P D 0.02, I2 D 51.5%) for studies in total population. In a subgroup analysis conducted by study region, the OR was 0.94 (95% CI, 0.78–1.14; Q D 17.8, P D 0.013, I2 D 60.7%) for studies in Asia, 0.96 (95% CI, 0.79–1.17; Q D
Moderate vs. Lowest Tea Consumption A meta-analysis of risk estimates of the incidence of pancreatic cancer for the moderate compared with the lowest tea consumption category (Table 3). The summary OR was 1.07 (95% CI, 0.86–1.35). There was no statistically significant heterogeneity across studies (Q D 15.74, P D 0.028, I2 D 55.5%; Fig. 4). No publication bias was observed from either visualization of the funnel plot, Begger’s test (P D 0.266) or Egger’s test (P D 0.583). When stratified analysis was conducted by study type, the OR was 1.07 (95% CI, 0.63–1.80; Q D 13.45, P D 0.004, I2 D 77.7%) for case-control studies and 1.07 (95% CI, 0.89–1.28) (Q D 2.18, P D 0.537, I2 D 0.00%) for the cohort studies. In a subgroup analysis conducted by sex, the OR was 1.17 (95% CI, 0.94–1.45; Q D 5.26, P D 0.262, I2 D 23.9%) for studies in males, 1.01 (95% CI, 0.79–1.28; Q D 6.1, P D 0.107, I2 D 50.8%) for studies in females, and 1.09 (95% CI, 0.93–1.28; Q D 12.14, P D 0.145, I2 D 34.1%) for studies in total population. When stratified analysis was conducted by study region, the OR was 0.98 (95% CI, 0.59–1.63; Q D 1.95, P D 0.163, I2 D 48.6%) for studies in Asia, 1.15 (95% CI, 0.28-4.73; Q D 10.42, P D 0.001, I2 D 90.4%) for studies in Europe, and 1.05 (95% CI, 0.89–1.24; Q D 0.80, P D 0.850, I2 D 0.00%) for studies in the United States. When stratified analysis was conducted by type of tea, the OR was 1.06 (95% CI, 0.59–1.94; Q D 14.29, P D 0.003, I2 D 79.0%) for studies in tea and 1.05 (95% CI, 0.89–1.24; Q D 0.80, P D 0.85, I2 D 0.0%) for studies in green tea. Stratification analysis was conducted without or with adjustment for BMI. The OR was 1.05 (95% CI, 0.45–2.44; Q D 13.04, P D 0.001, I2 D 84.7%) for no adjustment for BMI
1112 1–4 cups/daily
6430 and 9930
5–9 cups/daily
Moderate
2–4 times/day
Men Lifetime consumption (g/mo £ years of drinking) 1–3499 Women 1–3499
Lifetime consumption (liters) >3597 and 6430
3–4 cups/daily
Low
10 cups/daily Amount not known (but daily） 1–4 cups/daily 5 cups/daily Lifetime consumption (liters) >3597 and 6430 >6430 and 9930 >9930 5 cups/day Every day Men Lifetime consumption (g/mo £ years of drinking) 1–3499 3500–8499 8500 Women 1–3499 3500 2–4 times/day 5 time/day 1/day 1/day
Nutrition and Cancer Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/hnuc20
Consumption of Tea and Risk for Pancreatic Cancer: A Meta-Analysis of Published Epidemiological Studies a
b
a
a
Bing Chang , Lixuan Sang , Ying Wang , Jing Tong & Bing-Yuan Wang
a
a
Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China b
Department of Cadre Ward, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China Published online: 10 Sep 2014.
Click for updates To cite this article: Bing Chang, Lixuan Sang, Ying Wang, Jing Tong & Bing-Yuan Wang (2014) Consumption of Tea and Risk for Pancreatic Cancer: A Meta-Analysis of Published Epidemiological Studies, Nutrition and Cancer, 66:7, 1109-1123, DOI: 10.1080/01635581.2014.951730 To link to this article: http://dx.doi.org/10.1080/01635581.2014.951730
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Nutrition and Cancer, 66(7), 1109–1123 Copyright Ó 2014, Taylor & Francis Group, LLC ISSN: 0163-5581 print / 1532-7914 online DOI: 10.1080/01635581.2014.951730
Consumption of Tea and Risk for Pancreatic Cancer: A Meta-Analysis of Published Epidemiological Studies Bing Chang Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
Lixuan Sang
Downloaded by [George Washington University] at 20:37 07 February 2015
Department of Cadre Ward, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
Ying Wang, Jing Tong, and Bing-Yuan Wang Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
Epidemiologic studies on the relationship between tea consumption and pancreatic cancer are inconsistent. Therefore, we conducted a systematic search of databases and performed a meta-analysis to analyze the association between tea consumption and risk of pancreatic cancer. We searched Medline, EMBASE, ISI Web of Science, and the Cochrane library for studies of tea consumption and pancreatic cancer published up to December 2012. Subgroup analysis was conducted by study type, study region, sex, type of tea, without or with adjustment for smoking, and body mass index. We performed a meta-analysis of 8 casecontrol studies and 6 cohort studies. For pancreatic cancer, the summary odds ratio (OR) for highest vs. lowest was 0.95 (95% confidence interval (CI), 0.84–1.08). The summary OR for moderate vs. lowest was 1.07 (95% CI, 0.86–1.35). The summary OR for ever vs. lowest was 1.00 (95% CI, 0.86–1.16). The results of this meta-analysis suggested tea consumption is not related to pancreatic cancer risk, even at high doses. Because of the small number of studies, further prospective studies are needed.
BACKGROUND Pancreatic cancer is a common form of malignancy in the digestive system, usually with poor prognosis and high mortality. The World Health Organization Cancer Research Center estimates that 277,000 cases of pancreatic cancer are newly diagnosed each year worldwide (1). It is the 13th most common form of malignant tumor and the incidence rate is slightly higher in males than females. Over 60% of pancreatic cancers Submitted 6 June 2013; accepted in final form 12 June 2013. Address correspondence to Bing-Yuan Wang, Department of Cadre Ward, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China. E-mail: [email protected] Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/hnuc.
occur in developed countries. About 266,000 people die of pancreatic cancer each year worldwide, and the ratio between mortality and incidence rate is about 0.96 (1). The higher incidence of pancreatic cancer is in Japan where it reaches 16.9/ 100,000 (2). Worldwide the incidence of pancreatic cancer is gradually increasing along with prolonged lifespans. The diagnosis of pancreatic cancer is more difficult than other tumors of the digestive system because the pancreas is a retroperitoneal organ. This disease is usually at a late stage at diagnosis because of a lack of effective screening measures. Data from the National Cancer Institute show that tumors of only 8% of patients with pancreatic cancer are primary tumors at diagnosis and the 5-yr relative survival rate is 21.5% in these patients; 27% of patients have lymph node metastases at diagnosis and the 5-yr survival rate is 8.6%; and 53% of patients have distant metastases at diagnosis and the 5-yr survival rate is 1.8% (3). The low survival rate of pancreatic cancer is mainly due to its occult growth, with rapidly progressing growth stage, low surgical cure rate, and lack of effective treatment measures. The trend of different incidence rates and morbidity times worldwide suggests that environmental and genetic factors play important roles in the pathogenesis of pancreatic cancer. The treatment and survival time of patients have not been improved in past decades. Therefore, the prevention of pancreatic cancer is very important. It is generally agreed that many of the chemoprevention effects of tea are mediated by catechins. The major catechins in tea are epigallocatechin-3-gallate (EGCG), several studies have tried to investigate the relationship between EGCG and pancreatic cancer. Kim et al. indicates that EGCG inhibits invasion by inducing the expression of Raf kinase inhibitor 1109
1110
B. CHANG ET AL.
Downloaded by [George Washington University] at 20:37 07 February 2015
protein in AsPC‑1 human pancreatic adenocarcinoma cells through the modulation of histone deacetylase activity (4).The exact causes of pancreatic cancer and the natural history of occurrence are not very clear. However, many studies have shown that occurrence of pancreatic cancer is closely related to dietary factors. Although many epidemiological studies focus on the relationship between tea and pancreatic cancer, the data are inconclusive. Studies on the relationship between tea and pancreatic cancer from different countries have been reported since the 1990s, but meta-analysis is relatively rare. Therefore, we conducted a meta-analysis of all published studies to summarize the relationship between tea consumption and pancreatic cancer.
MATERIALS AND METHODS Literature Search Strategy We searched Medline (via PubMed; National Library of Medicine), EMBASE (Elsevier, Amsterdam, the Netherlands), ISI Web of Science (Institute for Scientific Information, Philadelphia, Pennsylvania), and the Cochrane library (Wiley, Chichester, UK) for studies published up to December 2012. Key words searched were as follows: (tea OR catechin OR beverages OR diet OR drinking OR lifestyle) AND pancreatic AND (cancer OR tumor OR neoplasm OR carcinoma) AND (risk). In addition, we also performed a manual search of reference cited in the published reviews. We restricted the search to papers published in English.
Inclusion and Exclusion Criteria The inclusion criteria were case-control or cohort study; data on the frequency of tea consumption; primary outcome defined as pancreatic cancer or pancreatic carcinoma; and relative risks (RRs) estimates, odds ratios (ORs), or hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs). Exclusion criteria included duplicate reports and insufficient data about tea consumption.
Data Extraction The following data were collected from each publication: the name of the first author, year of publication, the country where the study was conducted, study design, study population demographics, study period, sample size, type of outcome, consumption of coffee, number of exposed cases, the RRs or ORs or HRs and their 95% CIs, and covariates adjusted in the analysis. All data were extracted independently by 3 reviewers, and any disagreement was resolved by discussion among them. If results were published more than once, the results from the most recent one were selected. Because pancreatic cancer is rare, the OR was assumed to be the same as RR and HR, and all results are reported as OR for simplicity.
Statistical Analysis and Synthesis We quantified the relationship between tea consumption and pancreatic cancer risk by use of the DerSimonian and Laird (5) random effects model. We assessed the risk of pancreatic cancer for highest/moderate/ever vs. lowest consumption levels of tea. Because various sources of heterogeneity may exist owing to a variety of factors, we carried out subgroup analysis to investigate the influence of study design, study region, sex, type of tea, smoking, and body mass index (BMI). To estimate summary OR for various levels of tea consumption, we calculated the study-specific estimates for tea consumption (Table 1). We quantified the extent of heterogeneity using Q and Higgins I2 (5,6). A significant heterogeneity was defined as a P value < 0.10 or I2 > 50%. To investigate potential heterogeneity of among studies, subgroup analyses were conducted. Publication bias was assessed through visual inspection of funnel plot, Begger’s (7) and Egger’s tests (8). P < 0.05 for Begg’s or Egger’s tests was considered to be representative of a publication bias. All statistical analyses were performed with STATA (version 11.0; StataCorp, College Station, TX).
RESULTS Study Characteristics We identified 714 relevant articles on titles and abstracts from the meta-analysis shown in Fig. 1. We identified 14 articles on the relationship between tea consumption and the incidence of pancreatic cancer were published. However, 2 articles were excluded (9,10) because they did not provided risk ratios or 95% CIs. The remaining 12 articles are shown in Table 2 (11–22) (including a total of 3522 cases). Six of these were cohort studies (Michaud et al. included 2 cohort studies) (16–20), and 7 of these were case-control studies (Mizuno et al. included green tea and black tea were considered one study) (11–15,21,22). Of the selected studies, 3 were conducted in Europe (11,13,21), 3in the United States (12,17), and 7 in Asia (14–16,18–20,22). The estimated ORs of pancreatic cancer for highest versus lowest tea consumption are presented in Table 2.
Highest vs. Lowest Tea Consumption A meta-analysis of risk estimates of the incidence of pancreatic cancer for the highest compared with the lowest tea consumption category (Table 3). The summary OR was 0.95 (95% CI, 0.84–1.08). There was no statistically significant heterogeneity across studies (Q D 22.76, P D 0.045, I2 D 42.9%) (Fig. 2). No publication bias was observed from either visualization of the funnel plot, Begger’s test (P D 0.913) or Egger’s test (P D 0.673) (Fig. 3).
CONSUMPTION OF TEA AND RISK FOR PANCREATIC CANCER
714 relevant articles were identified on titles and abstracts 622 articles were excluded based on screening of titles or abstracts because they were reviews, ecological
Downloaded by [George Washington University] at 20:37 07 February 2015
studies, or laboratory studies
92 articles considered 78 design was incorrect or did not provide sufficient
1111
4.00, P D 0.135, I2 D 50%) for studies in Europe, and 0.97 (95% CI, 0.68–1.39; Q D 0.91, P D 0.64, I2 D 0%) for studies in the United States. When stratified analysis was conducted by type of tea, the OR was 0.97 (95% CI, 0.81–1.15; Q D 4.91, P D 0.427, I2 D 0%) for studies in tea, 0.96 (95% CI, 0.79–1.16; Q D 16.59, P D 0.011, I2 D 63.8%) for studies in green tea, and 0.53 (95% CI, 0.19-1.49) for study in black tea. Stratification analysis was conducted without or with adjustment for smoking. The OR was 0.98 (95% CI, 0.82– 1.07; Q D 15.63, P D 0.111, I2 D 36%) for no adjustment for smoking studies and 1.15 (95% CI, 0.74–1.79; Q D 6.37, P D 0.041, I2 D 68.6%) for the after adjustment for smoking studies. Stratification analysis was conducted without or with adjustment for BMI. The OR was 0.89 (95% CI, 0.67–1.18; Q D 18.01, P D 0.003, I2 D 72.2%) for no adjustment for BMI studies and 0.97 (95% CI, 0.84–1.12; Q D 4.44, P D 0.728, I2 D 0.00%) for after adjustment for BMI studies.
information
14 articles were selected for meta-analysis
2 articles were excluded because the articles did not provide risk ratios or 95% CIs and one article was published
12 articles (13 studies) were in Japanese selected for meta-analysis FIG. 1. Flowchart for search and selection of studies in the meta-analysis.
We assessed associations separately for study type, sex, study region, type of tea, and whether or not adjust smoking and BMI. The OR was 0.89 (95% CI, 0.76–1.04; Q D 18.61, P D 0.009, I2 D 62.4%) for case-control studies and 1.09 (95% CI, 0.88–1.35; Q D 1.99, P D 0.85, I2 D 0.0%) for the cohort studies. In a subgroup analysis conducted by sex, the OR was 1.01 (95% CI, 0.74–1.37; Q D 7.31, P D 0.199, I2 D 31.6%) for studies in males, 0.85 (95% CI, 0.50–1.43; Q D 14.94, P D 0.011, I2 D 66.5%) for studies in females, and 0.94 (95% CI, 0.71–1.25; Q D 22.7, P D 0.02, I2 D 51.5%) for studies in total population. In a subgroup analysis conducted by study region, the OR was 0.94 (95% CI, 0.78–1.14; Q D 17.8, P D 0.013, I2 D 60.7%) for studies in Asia, 0.96 (95% CI, 0.79–1.17; Q D
Moderate vs. Lowest Tea Consumption A meta-analysis of risk estimates of the incidence of pancreatic cancer for the moderate compared with the lowest tea consumption category (Table 3). The summary OR was 1.07 (95% CI, 0.86–1.35). There was no statistically significant heterogeneity across studies (Q D 15.74, P D 0.028, I2 D 55.5%; Fig. 4). No publication bias was observed from either visualization of the funnel plot, Begger’s test (P D 0.266) or Egger’s test (P D 0.583). When stratified analysis was conducted by study type, the OR was 1.07 (95% CI, 0.63–1.80; Q D 13.45, P D 0.004, I2 D 77.7%) for case-control studies and 1.07 (95% CI, 0.89–1.28) (Q D 2.18, P D 0.537, I2 D 0.00%) for the cohort studies. In a subgroup analysis conducted by sex, the OR was 1.17 (95% CI, 0.94–1.45; Q D 5.26, P D 0.262, I2 D 23.9%) for studies in males, 1.01 (95% CI, 0.79–1.28; Q D 6.1, P D 0.107, I2 D 50.8%) for studies in females, and 1.09 (95% CI, 0.93–1.28; Q D 12.14, P D 0.145, I2 D 34.1%) for studies in total population. When stratified analysis was conducted by study region, the OR was 0.98 (95% CI, 0.59–1.63; Q D 1.95, P D 0.163, I2 D 48.6%) for studies in Asia, 1.15 (95% CI, 0.28-4.73; Q D 10.42, P D 0.001, I2 D 90.4%) for studies in Europe, and 1.05 (95% CI, 0.89–1.24; Q D 0.80, P D 0.850, I2 D 0.00%) for studies in the United States. When stratified analysis was conducted by type of tea, the OR was 1.06 (95% CI, 0.59–1.94; Q D 14.29, P D 0.003, I2 D 79.0%) for studies in tea and 1.05 (95% CI, 0.89–1.24; Q D 0.80, P D 0.85, I2 D 0.0%) for studies in green tea. Stratification analysis was conducted without or with adjustment for BMI. The OR was 1.05 (95% CI, 0.45–2.44; Q D 13.04, P D 0.001, I2 D 84.7%) for no adjustment for BMI
1112 1–4 cups/daily
6430 and 9930
5–9 cups/daily
Moderate
2–4 times/day
Men Lifetime consumption (g/mo £ years of drinking) 1–3499 Women 1–3499
Lifetime consumption (liters) >3597 and 6430
3–4 cups/daily
Low
10 cups/daily Amount not known (but daily） 1–4 cups/daily 5 cups/daily Lifetime consumption (liters) >3597 and 6430 >6430 and 9930 >9930 5 cups/day Every day Men Lifetime consumption (g/mo £ years of drinking) 1–3499 3500–8499 8500 Women 1–3499 3500 2–4 times/day 5 time/day 1/day 1/day
