MCO Molecular and Clinical Oncology 2049-9450 2049-9469 D.A. Spandidos 10.3892/mco.2015.489 MCO-0-0-489 Articles Tea consumption and risk of gallbladder cancer: A meta-analysis of epidemiological studies ZHUGUANGWEI1 2 HUAJIN3 WANGZHIJIAN4 SHEFEIFEI2 CHENYANLING1 2 Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Union Hospital, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China Key Laboratory of Ministry of Education for Gastrointestinal Cancer and Key Laboratory of Tumor Microbiology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China The First Clinic Medical College and The First Hospital, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China The Affiliated People's Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350005, P.R. China Correspondence to: Professor Yanling Chen, Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Union Hospital, Fujian Medical University, 29 Xin-Quan Road, Fuzhou, Fujian 350001, P.R. China, E-mail: ylchen@medmail.com.cn Professor Feifei She, Key Laboratory of Ministry of Education for Gastrointestinal Cancer and Key Laboratory of Tumor Microbiology, School of Basic Medical Sciences, Fujian Medical University, 1 Xue-Yuan Road, Fuzhou, Fujian 350001, P.R. China, E-mail: shefeifei@yeah.net 05 2015 21 01 2015 3 3 613 618 22082014 08012015 Copyright © 2015, Spandidos Publications 2015

Previous epidemiological studies investigating the association between tea consumption and the risk of gallbladder cancer have yielded inconsistent results. Therefore, we aimed to assess this association by conducting a meta-analysis of all available studies. A search was conducted through Pubmed, Embase, Chinese Biomedical literature Database and China Knowledge Resource Integrated Database to identify relevant studies on tea consumption and the risk of gallbladder cancer. A random-effects model was used to calculate the overall combined risk estimates. Six studies (4 case-control and 2 cohort studies), involving a total of 753 patients and 115,349 controls, were included in this meta-analysis. The overall combined odds ratio (OR) for tea consumption and gallbladder cancer was 0.67 [95% confidence interval (CI): 0.40–1.12, P=0.13]. Similar results were obtained for the high or moderate tea consumption vs. the low/non-consumption groups. However, our meta-analysis identified a significant association between tea consumption and reduced gallbladder cancer risk in women (OR=0.46, 95% CI: 0.26–0.81, P=0.008), but not in men (OR=0.43, 95% CI: 0.12–1.59, P=0.21). Therefore, the results of the present meta-analysis suggest that, according to the currently available epidemiological studies, tea consumption may reduce the risk of gallbladder cancer in women, but not in men. Further epidemiological studies are required to determine the association between tea consumption and the risk of gallbladder cancer.

 tea consumption gallbladder carcinoma meta-analysis epidemiological studies Introduction

Gallbladder cancer is a rare and highly fatal disease and is the most common malignant neoplasm of the extrahepatic biliary tract and the seventh most common gastrointestinal carcinoma (1). There were an estimated 10,310 cases of gallbladder cancer diagnosed in 2013 (2). Although gallbladder cancer remains an uncommon disease, it exhibits a high incidence in certain regions, such as Chile, where it is the most common cause of cancer-related mortality (3). We previously demonstrated the significance of lymph node metastasis (4). Although the etiology of the gallbladder cancer remains unknown, genetic, environmental and infectious factors, as well as the presence of gallstones, are considered to play important roles (5). The majority of the risk factors implicated in the development of gallbladder cancer are associated with inflammation (6).

Tea is one of the most popular beverages worldwide, second only to water, and is obtained from the steamed or pan-fried leaves of Camellia sinensis (7). Tea contains several polyphenols, known as catechins, such as epigallocatechin-3 gallate (EGCG), epigallocatechin (EGC) and epicatechin-3 gallate (ECG), which are considered to prevent the development of certain human diseases (8). Previous cellular and animal xenograft studies have reported that tea or its active components, EGCG, EGC and ECG, may possess antiproliferative, antimutagenic, antioxidant and antibacterial properties (9–13). In general, tea may prevent multifarious cancers at the cell and animal level. Tea was found to induce the apoptosis of gbc-sd human gallbladder carcinoma cells (14,15).

The results of epidemiological studies, such as cohort and case-control studies, investigating the association between tea consumption and gallbladder cancer risk over the last century, have been inconsistent. Certain studies reported that tea consumption significantly decreased the risk of gallbladder cancer, whereas others reported a non-significant negative correlation (16–21). However, to the best of our knowledge, there is currently no published meta-analysis investigating the association between tea consumption and gallbldder cancer risk.

The aim of the present study was to assess the association between tea consumption and the risk of gallbladder cancer through conducting a meta-analysis of relevant case-control and cohort studies.

 Materials and methods <sec> <title>Literature search

A literature search was conducted through Pubmed, Embase, Chinese Biomedical literature Database (CBM) and China Knowledge Resource Integrated Database (CNKI), to identify epidemiological studies investigating the association of tea consumption with gallbladder cancer risk. As regards the outcome, the articles were identified using the medical subject headings (mesh) terms ‘gallbladder neoplasm’ or ‘gallbladder carcinoma’ or ‘gallbladder cancer’ and ‘tea’ or ‘polyphenols’. As regards study design, the articles were identified using the mesh terms ‘case-control’ or ‘cohort’ or ‘prospective studies’. The reference lists of the retrieved articles were manually searched to identify potentially relevant publications. All the studies meeting the eligible criteria listed below were included in our meta-analysis.

 Inclusion criteria

We reviewed the abstracts of all the identified studies. Further study selection was performed using the following inclusions: i) the exposure of interest was tea consumption; ii) the outcome of interest was gallbladder cancer; iii) the design of the study was cohort, case-control or prospective; and iv) the odds ratio (OR), relative risk or hazard ratio were reported.

The search only involved studies conducted on humans and the publication language was restricted to English and Chinese. If publications were duplicated or shared in more than one study using a different language, we selected the most recent edition and English.

 Data extration

Two reviewers (G.W.Z. and J.H.) independently extracted data on the characteristics of the eligible studies retrieved from the databases according to the above mentioned selection criteria, using a standardized data extraction form. The following data were recorded: author name, study design, country, sample size, study period, exposure to tea consumption and study results. Any disagreements were resolved through discussion and consensus with a third author (Z.J.W.).

 Statistical analyses

OR with 95% confidence interval (CI) was used as a common measure of the association between tea consumption and the risk of gallbladder cancer across studies. For the purposes of the present analysis, tea consumption was coded as a three-level indicator variable, with non/low, moderate and high consumption (Table I). We investigated possible heterogeneity in the results across the studies using the Cochran's Q test. The I2 statistic, which is a quantitative measure of inconsistency across publications, was also used (22). Studies with an I2 statistic of 25–50, 50–75 and >75% were considered to exhibit low, moderate and high heterogeneity, respectively (22). The random-effects model was used when significant (moderate and high) heterogeneity was observed among studies (23). Potential publication bias was assessed by visually inspecting the Begg's funnel plots. P<0.05 was considered to indicate a statistically significant difference. All the statistical analyses were performed using Review Manager software, version 5.2 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark).

 Results <sec> <title>Identification of relevant studies

Our meta-analysis included a total of 6 studies [4 case-control (17,19–21) and 2 cohort studies (16,18)] published between 1987 and 2012. The literature search and selection process is summarized in Fig. 1. The four databases (Pubmed, Embase, CBM and CNKI) and the search through the bibliographies of relevant articles yielded 453 articles. A total of 82 articles were excluded due to being duplicate studies. The remaining 371 articles were reviewed; of these, the majority were excluded following title and abstract review (reviews, letters, or studies not relevant to our meta-analysis were excluded), leaving 10 studies for full-text review. A further 2 studies were excluded [one study with unavailable data for analysis (24) and one study published using English and Chinese (25)]. Following fundamental research exclusion of another 2 studies (14,15), a total of 6 studies were included in our present meta-analysis.

 Study characteristics

The characteristics of the 6 studies included in this meta-analysis are summarized in Table I. The case/control sample size of the studies ranged between 41/184 and 368/69,310. Among these studies, 1 study only enrolled a female population (16). The definition of tea consumption level (high/moderate vs. low/non-consumption) are also reported in Table I.

 Tea consumption and the risk of gallbladder cancer

A total of 6 studies were included in the meta-analysis investigating the association between tea consumption and the risk of gallbladder cancer. Overall, no significant association was observed between tea consumption and gallbladder cancer risk (OR=0.67, 95% CI: 0.40–1.12, P=0.13) in a random-effects model. There was significant heterogeneity among the studies (I2=82%; P<0.0001) (Fig. 2). Subsequently, sensitivity analyses were conducted to identify the potential source of heterogeneity and to assess the effect of different exclusion criteria on the combined estimates. Exclusion of women from studies on tea and gallbladder cancer risk yielded similar results (OR=0.62, 95% CI: 0.35–1.10, P=0.10), with significant heterogeneity (I2=81%; P=0.0003) (16). Following exclusion of 3 studies with a small sample size, the pooled results were not affected (OR=1.09, 95% CI: 0.80–1.48, P=0.60) and no significant heterogeneity was observed among the remaining studies (I2=0%; P=0.76) (17,19,20).

 Levels of tea consumption and gallbladder cancer risk

We performed meta-analyses based on the level of tea consumption to investigate the effect of different tea consumption levels on gallbladder cancer risk. The results were relatively consistent and demonstrated that there was no significant difference bettween high/moderate vs. low/non-consumption in reducing the risk of gallbladder cancer (OR=0.57, 95% CI: 0.25–1.29, P=0.18; Fig. 3A; and OR=0.62, 95% CI: 0.33–1.14, P=0.12; Fig. 3B, respectively).

 Comparison of women and men regarding tea consumption and the risk of gallbladder cancer

When studies were divided by gender, there was a significant decrease in the risk of gallbladder cancer associated with tea consumption in women (OR=0.46, 95% CI: 0.26–0.81, P=0.008; Fig. 4A). However, no association between tea consumption and the risk of gallbladder cancer was observed in men (OR=0.43, 95% CI: 0.12–1.59, P=0.21; Fig. 4B).

 Publication bias

In our meta-analysis, the potential presence of publication bias was assessed by visual inspection of the Begg's funnel plots, which indicated that there was no significant publication bias (Fig. 5).

 Discussion

To the best of our knowledge, this is the first meta-analysis to evaluate the association between tea consumption and gallbladder cancer. This meta-analysis of epidemiological studies (4 case-control and 2 cohort studies) investigating the association between tea and gallbladder cancer risk, demonstrated that tea consumption did not reduce the risk of gallbladder cancer. Similar results were obtained for high or moderate vs. low/non-consumption. However, our meta-analysis identified a significant association between tea consumption and reduced gallbladder cancer risk in women, but not in men. The combined estimates were robust across sensitivity analyses and exhibited no publication bias.

A number of studies conducted in vitro and in vivo reported that tea may protect against different types of cancer (26–31). Therefore, several clinical and epidemiological studies were conducted, which, however, yielded conflicting results regarding tea consumption and the risk of breast (32,33), lung (34) and renal cancer (35,36). In order to obtain more convincing results, certain meta-analyses were conducted for other types of cancer, which also yielded inconsistent results (37–40).

The results of the epidemiological studies on the association between tea consumption and the risk of gallbladder cancer included in our meta-analysis were inconsistent: 2 studies reported that tea intake decreased the risk of gallbladder cancer (17,20), 3 studies reported opposing results (16,18,21) and 1 study reported that tea intake reduced the risk of gallbladder cancer in women, but not in men (19). Therefore, we performed a meta-analysis assessing the association between tea consumption and gallbladder cancer.

Our meta-analysis found that there was a significant association between tea consumption and reduced gallbladder cancer risk in women, but not in men. There may be a reasonable explanation for this finding: lifestyle factors, such as smoking and alcohol consumption may be responsible for the tea intake not reducing the risk of gallbladder cancer in men, due to the high prevalence of smoking and alcohol consumption among men (41,42), which may eliminate the protective effect of tea. Another possible explanation for the significant protective effect of tea in women may be relevant to the effects of tea on estrogen biosynthesis. Previous studies demonstrated that high levels of estrogens were consistently associated with a high risk of gallbladder cancer in women (43–45). Experimental data from animal and cell models suggested that tea may affect estrogen metabolism, although the detailed mechanisms underlying this effect remain unknown (46,47).

As is often the case with meta-analyses, ours had certain limitations. First, our analysis was based on 6 studies with widely variable sample sizes, which may be the origin of the heterogeneity of our meta-analysis. Although we performed a funnel plot for the outcomes, the limited number of studies makes it difficult to explain the result of publication bias. Second, certain detailed information could not be obtained, such as 2 studies that did not provide a precise record of gallbladder cancer cases (16,17), although gallbladder cancer is the most common malignant neoplasm of the extrahepatic biliary tract and accounts for the majority of extrahepatic biliary cancers (1); therefore, the studies were included in our meta-analysis. Moreover, there are several types of tea, including green, oolong and black tea, which may inhibit cancer development through different mechanisms. Therefore, our study results may not apply to all types of tea. Finally, missing and/or unpublished data may lead to bias.

In conclusion, our meta-analysis suggests that, according to the currently available epidemiological studies, tea consumption may reduce the risk of gallbladder cancer in women, but not in men. Due to the limitations of our study, further epidemiological studies are required to determine the association between tea consumption and the risk of gallbladder cancer.

 Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (no. 81272373), the Key Project of Science and Technology Research Program of Fujian Province (no. 2009Y0024), the Key Project of Science Research of Fujian Medical University (no. 09ZD017) and the National Clinical Key Specialty Construction Project (General Surgery) of China.

 References DonohueJHStewartAKMenckHRThe National Cancer Data Base report on carcinoma of the gallbladder, 1989–1995Cancer8326182628199810.1002/(SICI)1097-0142(19981215)83:12<2618::AID-CNCR29>3.0.CO;2-H9874470 SiegelRNaishadhamDJemalACancer statistics2013 CA Cancer J Clin631130201310.3322/caac.21166 RandiGMalvezziMLeviFEpidemiology of biliary tract cancers: an updateAnn Oncol20146159200910.1093/annonc/mdn53318667395 DuQJiangLWangXQPanWSheFFChenYLEstablishment of and comparison between orthotopic xenograft and subcutaneous xenograft models of gallbladder carcinomaAsian Pac J Cancer Prev1537473752201410.7314/APJCP.2014.15.8.374724870787 WernbergJALucarelliDDGallbladder cancerSurg Clin North Am94343360201410.1016/j.suc.2014.01.00924679425 Albores-SaavedraJAlcantra-VazquezACruz-OrtizHHerrera-GoepfertRThe precursor lesions of invasive gallbladder carcinoma Hyperplasia, atypical hyperplasia and carcinoma in situCancer45919927198010.1002/1097-0142(19800301)45:5<919::AID-CNCR2820450514>3.0.CO;2-47260842 JankunJSelmanSHSwierczRSkrzypczak-JankunEWhy drinking green tea could prevent cancerNature387561199710.1038/423819177339 RetoMFigueiraMEFilipeHMAlmeidaCMChemical composition of green tea (Camellia sinensis) infusions commercialized in PortugalPlant Foods Hum Nutr62139144200710.1007/s11130-007-0054-817899383 JochmannNBaumannGStanglVGreen tea and cardiovascular disease: from molecular targets towards human healthCurr Opin Clin Nutr Metab Care11758765200810.1097/MCO.0b013e328314b68b18827581 ChengSDingLZhenYProgress in studies on the antimutagenicity and anticarcinogenicity of green tea epicatechinsChin Med Sci J623323819911813062 GuptaSSahaBGiriAKComparative antimutagenic and anticlastogenic effects of green tea and black tea: a reviewMutat Res5123765200210.1016/S1383-5742(02)00024-812220589 LambertJDEliasRJThe antioxidant and pro-oxidant activities of green tea polyphenols: a role in cancer preventionArch Biochem Biophys5016572201010.1016/j.abb.2010.06.01320558130 CabreraCArtachoRGimenezRBeneficial effects of green tea - a reviewJ Am Coll Nutr257999200610.1080/07315724.2006.1071951816582024 LianCQZhangJChenZDChanges of free calcium ion concentration and mitochondrial membrane potential during apoptosis of human gallbladder carcinoma GBC-SD cells induced by tea polyphenolsChin J Biol254494522012 LianCQXiaJGaoQZhangJA study on apoptosis in human gallbladder carcinoma GBC-SD cells induced by tea polyphenolsChin J Gerontol32207720802012 NechutaSShuXOLiHLProspective cohort study of tea consumption and risk of digestive system cancers: results from the Shanghai Women's Health StudyAm J Clin Nutr9610561063201210.3945/ajcn.111.03141923053557 YenSHsiehCCMacMahonBExtrahepatic bile duct cancer and smoking, beverage consumption, past medical history, and oral contraceptive useCancer5921122116198710.1002/1097-0142(19870615)59:12<2112::AID-CNCR2820591226>3.0.CO;2-H3567872 NaganoJKonoSPrestonDLMabuchiKA prospective study of green tea consumption and cancer incidence, Hiroshima and Nagasaki (Japan)Cancer Causes Control12501508200110.1023/A:101129732669611519758 ZhangXHAndreottiGGaoYTTea drinking and the risk of biliary tract cancers and biliary stones: a population-based case-control study in Shanghai, ChinaInt J Cancer11830893094200610.1002/ijc.2174816395699 ZatonskiWALa VecchiaCPrzewozniakKMaisonneuvePLowenfelsABBoylePRisk factors for gallbladder cancer: a Polish case-control studyInt J Cancer51707711199210.1002/ijc.29105105081612778 La VecchiaCNegriEFranceschiSD'AvanzoBBoylePTea consumption and cancer riskNutr Cancer172731199210.1080/016355892095141701574442 HigginsJPThompsonSGDeeksJJAltmanDGMeasuring inconsistency in meta-analysesBMJ327557560200310.1136/bmj.327.7414.55712958120 DerSimonianRLairdNMeta-analysis in clinical trialsControl Clin Trials7177188198610.1016/0197-2456(86)90046-23802833 PandeyMShuklaVKDiet and gallbladder cancer: a case-control studyEur J Cancer Prev11365368200210.1097/00008469-200208000-0000812195163 ZhangXHGaoYTRashidATea consumption and risk of biliary tract cancers and gallstone disease: a population-based case-control study in Shanghai, ChinaChin J Oncol276676712005(In Chinese) YangCSMaliakalPMengXInhibition of carcinogenesis by teaAnnu Rev Pharmacol Toxicol422554200210.1146/annurev.pharmtox.42.082101.15430911807163 ChenDDanielKGKuhnDJGreen tea and tea polyphenols in cancer preventionFront Biosci926182631200410.2741/142115358585 HuoCWanSBLamWHThe challenge of developing green tea polyphenols as therapeutic agentsInflammopharmacology16248252200810.1007/s10787-008-8031-x18815735 AdhamiVMSiddiquiIASarfarazSEffective prostate cancer chemopreventive intervention with green tea polyphenols in the TRAMP model depends on the stage of the diseaseClin Cancer Res1519471953200910.1158/1078-0432.CCR-08-233219276266 BettuzziSRizziFBelloniLClinical relevance of the inhibitory effect of green tea catechins (GtCs) on prostate cancer progression in combination with molecular profiling of catechin-resistant tumors: an integrated viewPol J Vet Sci105760200717388027 ScaltritiMBelloniLCaporaliAMolecular classification of green tea catechin-sensitive and green tea catechin-resistant prostate cancer in the TRAMP mice model by quantitative real-time PCR gene profilingCarcinogenesis2710471053200610.1093/carcin/bgi28716314398 InoueMTajimaKMizutaniMRegular consumption of green tea and the risk of breast cancer recurrence: follow-up study from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC)Japan. Cancer Lett167175182200110.1016/S0304-3835(01)00486-4 WuAHYuMCTsengCCHankinJPikeMCGreen tea and risk of breast cancer in Asian AmericansInt J Cancer106574579200310.1002/ijc.1125912845655 Arts ICA review of the epidemiological evidence on tea, flavonoids, and lung cancerJ Nutr1381561S1566S200818641207 De StefaniEFierroLMendilaharsuMMeat intake, ‘mate’ drinking and renal cell cancer in Uruguay: a case-control studyBr J Cancer7812391243199810.1038/bjc.1998.6619820187 HuJMaoYDesMeulesMCsizmadiIFriedenreichCMeryLCanadian Cancer Registries Epidemiology Research Group: Total fluid and specific beverage intake and risk of renal cell carcinoma in CanadaCancer Epidemiol33355362200910.1016/j.canep.2009.10.00419896918 ZhongSChenZYuXTea consumption and leukemia risk: a meta-analysisTumour Biol3552055212201410.1007/s13277-014-1675-924504676 HuZHLinYWXuXNo association between tea consumption and risk of renal cell carcinoma: a meta-analysis of epidemiological studiesAsian Pac J Cancer Prev1416911695201310.7314/APJCP.2013.14.3.169123679258 LinYWHuZHWangXTea consumption and prostate cancer: an updated meta-analysisWorld J Surg Oncol1238201410.1186/1477-7819-12-3824528523 MyungSKBaeWKOhSMGreen tea consumption and risk of stomach cancer: a meta-analysis of epidemiologic studiesInt J Cancer124670677200910.1002/ijc.2388018973231 YuanJMSunCButlerLMTea and cancer prevention: epidemiological studiesPharmacol Res64123135201110.1016/j.phrs.2011.03.00221419224 GaoYTMcLaughlinJKBlotWJJiBTDaiQFraumeniJFJrReduced risk of esophageal cancer associated with green tea consumptionJ Natl Cancer Inst86855858199410.1093/jnci/86.11.8558182766 PandeyMShuklaVKLifestyle, parity, menstrual and reproductive factors and risk of gallbladder cancerEur J Cancer Prev12269272200310.1097/00008469-200308000-0000512883378 NakagakiMNakayamaFEffect of female sex hormones on lithogenicity of bileJpn J Surg121318198210.1007/BF024690097069944 ChenAHuminerDThe role of estrogen receptors in the development of gallstones and gallbladder cancerMed Hypotheses36259260199110.1016/0306-9877(91)90145-O1787822 Kuruto-NiwaRInoueSOgawaSMuramatsuMNozawaREffects of tea catechins on the ERE-regulated estrogenic activityJ Agric Food Chem4863556361200010.1021/jf000848711312808 NagaiMConneyAHZhuBTStrong inhibitory effects of common tea catechins and bioflavonoids on the O-methylation of catechol estrogens catalyzed by human liver cytosolic catechol-O-methyltransferaseDrug Metab Dispos32497504200410.1124/dmd.32.5.49715100171

Flow chart of the literature search and study selection process.

Forest plot showing the risk estimates from case-control and cohort studies assessing the association between tea consumption and the risk of gallbladder cancer. CI, confidence interval.

(A) Forest plot showing the risk estimates for high vs. low/non-consumption of tea and the risk of gallbladder cancer. (B) Forest plot showing the risk estimates for moderate vs. low/non-consumption of tea and the risk of gallbladder cancer. CI, confidence interval.

(A) Forest plot showing the risk estimates for tea consumption and the risk of gallbladder cancer in women. (B) Forest plot showing the risk estimates for tea consumption and the risk of gallbladder cancer in men. CI, confidence interval.

Funnel plot of tea consumption and the the risk of gallbladder cancer. OR, odds ratio; SE, standard error.

Characteristics of the studies included in the meta-analysis.

Study (year) Design Study period Country No. of cases/controls Low/non-consumption Moderate consumption High consumption (Refs.)
Nechuta et al (2012) Cohort 1996–2000 China 83/69,310 Never NR Current (16)
Yen et al (1987) Case-control 1975–1979 USA         67/272 Never/occasionally/1–2 cups/day 3–4 cups/day ≥5 cups/day (17)
Nagano et al (2001) Cohort 1979–1994 Japan       122/38,540 0–1 times/day 2–4 times/day ≥5 times/day (18)
Zhang et al (2006) Case-control 1997–2001 China       368/902 Never M: <81,600 g lifetime; M: >81,600 g lifetime; (19)
F: <24,600 g lifetime F: <24,600 g lifetime
Zatonski et al (1992) Case-control 1985–1988 Poland        72/184 Never <6,570 lifetime drinks >6,570 lifetime drinks (20)
La Vecchia et al (1992) Case-control 1983–1990 Italy        41/6,141 No tea consumption NR Tea consumption (21)

NR, not reported; M, male; F, female.