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Coffee, tea, and maté may cause esophageal cancer (EC) by causing thermal injury to the esophageal mucosa. If so, the risk of EC attributable to thermal injury could be large in populations in which these beverages are commonly consumed. In addition, these drinks may cause or prevent EC via their chemical constituents. Therefore, a large number of epidemiologic studies have investigated the association of an indicator of amount or temperature of use of these drinks or other hot foods and beverages with risk of EC.
We conducted a systematic review of these studies, and report the results for amount and temperature of use separately. By searching PubMed and the ISI, we found 59 eligible studies.
For coffee and tea, there was little evidence for an association between amount of use and EC risk; however, the majority of studies showed an increased risk of EC associated with higher drinking temperature which was statistically significant in most of them. For maté drinking, the number of studies was limited, but they consistently showed that EC risk increased with both amount consumed and temperature, and these two were independent risk factors. For other hot foods and drinks, over half of the studies showed statistically significant increased risks of EC associated with higher temperature of intake.
Overall, the available results strongly suggest that high-temperature beverage drinking increases the risk of EC. Future studies will require standardized strategies that allow for combining data, and results should be reported by histological subtypes of EC.
Recurrent thermal injury to the esophageal mucosa due to consuming large amounts of hot drinks has long been suspected to be a risk factor for esophageal cancer (EC). In 1939, WL Watson, after reviewing clinical records from 771 EC cases, wrote: “thermal irritation is probably the most constant factor predisposing to the cancer of the esophagus”.1 If hot drinks indeed cause EC, they can explain a large proportion of all cases in populations in which drinking tea, coffee, or maté (an herbal infusion of Ilex paraguariensis, commonly consumed in several South American countries), or eating hot foods are common. Nevertheless, the association of hot drinks with EC has been questioned both based on biologic reasons and empirical evidence.
It has been argued that the temperature of hot foods and drinks may fall rapidly in the mouth and oropharynx so that it cannot cause thermal injury to the esophageal mucosa.2 To test this hypothesis, De Jong and colleagues measured intraesophageal temperature after consuming hot drinks. The results of their study showed that drinking hot beverages could substantially increase the intra-esophageal temperature and this increase was a function of the initial drinking temperature and more importantly, the size of the sip.3 For example, drinking 65 °C coffee increased the intra-esophageal temperature by 6–12 °C, depending on the sip size.3
Tea, coffee, and maté may affect cancer risk not only through thermal effects but also via their chemical constituents. Although some studies have shown mutagenic effects for tea, coffee, and unprocessed maté herb (Ilex paraguariensis) extracts,4–10 a number of more recent experimental studies in animals have reported cancer preventive activities for these beverages (reviewed in refs. 11–15). A number of epidemiological studies have investigated a possible effect of these beverages on cancer risk. With respect to gastrointestinal cancers, recent meta-analyses did not find any significant association between tea drinking and gastric and colorectal cancers,16–18 but coffee drinking was shown to be inversely associated with risk of liver cancer.19,20
In 1990, a Working Group of the International Agency for Research on Cancer (IARC) concluded that there was not sufficient evidence to recognize tea, coffee, or maté, in toto, as risk factors of human cancer, but they found that drinking hot maté was a probable risk factor in humans.21 The strongest evidence was for an association with EC. Since then, a large number of additional studies have investigated the association of the beverages and EC. We conducted a systematic review of the results of epidemiologic studies on the association of tea, coffee, or maté drinking or of high-temperature food consumption with EC.
We conducted a comprehensive search of the PubMed and ISI-Web of Knowledge databases for all case-control or cohort studies published in English language on the association of tea, coffee, maté, or other hot drinks or high temperature foods and risk of EC. All results were updated on January 23, 2009. The following terms were used in the PubMed Database search: “(esophag* OR oesophag*) AND (cancer OR carcinoma OR adenocarcinoma OR neoplasm OR neoplasia OR neoplastic) AND (tea OR mate OR coffee OR beverage)”; the search was repeated by replacing the last phrase with “(liquid OR drinks OR alcohol OR food) AND (hot OR cold OR warm OR temperature)”. The same terms were used to search text words in the ISI Database. In addition, references cited in the identified articles were searched manually. Two of the authors (FI and FK) reviewed the search results to reduce the possibility of missing the published papers.
Using the above-mentioned approach, a total of 536 articles were retrieved. Figure 1 shows a summary of the article selection process. After reading the abstracts of the retrieved articles, we excluded 417 articles because they were not case-control or cohort studies of hot drinks and EC; the excluded articles were reviews, animal studies, in vitro studies, case-series, studies of cancers other than EC, or studies of treatment and complications of EC. In case of any doubt, we also reviewed the full texts of those articles. After reviewing the full texts of the remaining 119 articles, we excluded another 57 because they did not present data on the variables of interest, but we found an additional 14 articles by searching the references of the articles. We also included a study which was in press at the time of our review.22 Therefore, a total of 77 relevant articles were found. Of these, 7 articles 23–29 were excluded because they reported data on EC in combination with other cancers and an additional 10 publications 30–39 were excluded because their results were reported in other publications or in combined analyses. One more study that referred to drinking of hot Calvados,40 a strong spirit which is a well established cause of EC, was excluded because separating the effect of temperature from that of the spirit per se would be difficult. Finally, a total of 59 full-text articles were included in this systematic review.22,41–98
Tea, coffee, and maté constitute the three major types of hot drinks consumed around the world. Therefore, we present data for each one of these, as well as for the mixed group of other hot foods and drinks, in separate tables. The two main variables of interest were: 1) an indicator of amount consumed (frequency per day, amount per day, duration of use, or a composite variable indicating cumulative use); and 2) temperature.
The etiological factors responsible for the two main histological of EC, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), may be different, and any role of hot drinks and foods might be more relevant for ESCC etiology.99 Therefore, where data are available, we present the results for ESCC and EAC separately.
Where both crude and adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported in the paper, we only present the adjusted results. A small number of studies showed crude numbers but not ORs and 95% CIs, in which case we calculated these statistics using simple logistic regression models and present them. Throughout the article, P values < 0.05 were considered as statistically significant.
After excluding duplicate publications, we found 38 papers, published between 1974 and 2008, that reported on the association of tea drinking with EC (Table 1). These included 33 individual case-control studies, a pooled analysis of 5 case-control studies, a pooled analysis of 2 case-control studies, and 3 prospective studies. The studies were conducted in United States, South America, Europe, South-Africa, Middle-East, and South and East Asia, and included both high-risk and low-risk regions. Two of the prospective studies were from Japan and one was from China. There were large differences in study size, but the majority of the studies had between 100 and 400 EC cases. Whereas some studies described the type of tea consumed (e.g., green tea or black tea), the large majority did not report on tea type; however, black tea represents the predominant type of tea traditionally drunk in most regions outside East Asia.21
Most studies (n = 33) provided results for one of the indicators of amount consumed, e.g., amount per day, frequency per day, duration of use, or an indicator of cumulative use. However, not all studies reported ORs (95% CIs) or crude numbers. There was no clear pattern of association between amount of tea consumed and EC risk; 7 studies showed an increase in risk (4 were statistically significant), and this was counterbalanced by 15 individual studies and a pooled analysis of 5 case-control studies that showed an inverse association between tea drinking and EC risk, either in the main analyses or in subgroup analyses (the association in 8 studies was statistically significant). Four studies reported ORs close to one, on both sides of the null line, which were not statistically significant. In addition, 6 other studies only stated that the results were not statistically significant, without reporting detailed results. We did not find a clear pattern of association by geographic region. However, the majority of the inverse associations were from East-Asian countries, especially China, where mostly green tea is used.
Results for the association of tea drinking temperature and EC were reported in 14 publications. Of these, 7 individual case-control studies, a combined analysis of 5 other case-control studies, and a prospective study found an increased risk; of these, the association was statistically significant in 8 studies. Two case-control studies reported statistically non-significant inverse associations, and 3 other studies only stated that the results were not statistically significant, without reporting crude numbers or ORs.
We found 22 independent papers, published between 1974 and 2008, that reported on the association between coffee intake and EC (Table 2). These included 17 individual case-control studies, a pooled analysis of 5 case-control studies, a pooled analysis of 2 case-control studies, and 3 cohort studies. Most reports (n = 14) were from the United States or Europe. Most studies included between 100 and 400 EC cases.
Most studies (n = 20) reported one of the indicators of amount consumed and EC. Four case-control studies showed statistically non-significant positive associations. Seven studies reported an inverse association between coffee drinking and EC risk, of which only 1 prospective study from Japan and a combined analysis of 2 case-control studies from Italy and Switzerland showed statistically significant results for drinking 3 or more cups per day. Four other studies, including 2 prospective studies, showed non-significant results with ORs close to one, on both sides of null line. The remaining 5 studies only reported that the results were not statistically significant.
Six individual case-control studies and a pooled analysis of 5 other case-control studies reported on temperature of coffee consumption in relation to EC risk. Of these, 2 individual studies and the pooled analysis showed an increased risk with drinking hot or very hot coffee, either in the main analyses or in subgroup analyses; 2 studies suggested statistically non-significant inverse associations, and 2 other studies only reported that the results were not statistically significant.
We found 4 independent papers, including 3 individual case-control studies and a combined analysis of 5 other case-control studies. These reports were published between 1985 and 2008 and all came from South American countries (Table 3).
All reports showed significantly increased EC risk with amount consumed, with approximately 3-fold higher risk in those in the highest category of consumption compared to those who did not consume maté. The pooled analysis of the case-control studies found that amount per day and duration of drinking both increased risk.
Three of these publications reported on the association of temperature of maté drinking and EC risk and all showed significant increased risk with increasing temperature. Mutual adjustment for temperature and amount in the pooled analysis suggested that amount and temperature of use were independent risk factors for EC.
We found 19 publications (17 individual case-control studies, a combined analysis of 5 other case-control studies, and 1 prospective study) that presented results on the association of consumption of high temperature food, other drinks, or all beverages combined with risk of EC (Table 4). The reports were published between 1974 and 2008, and the studies were conducted in South Americas, Europe, Africa, and South and East Asia. For this category, we only present results on temperature.
In all, 11 individual case-control studies and the combined analysis showed positive associations (11 were statistically significant), whereas 2 case-control studies found statistically non-significant inverse associations. Two case-control studies and the prospective study reported ORs close to one, on both sides of null line, with no statistically significant association. Two other studies only stated that the results were not statistically significant, without reporting crude numbers or ORs.
A summary of the associations between amount or temperature of consumed tea, coffee, or maté, or consumption of high temperature food or other beverages, and risk of EC is presented in Table 5.
In this systematic review, we collected the published literature on the association between consuming tea, coffee, maté, or other high-temperature beverages or foods and risk of EC. We analyzed the results for amount consumed and temperature of drinking separately. For tea and coffee, there was little evidence that the amount consumed was associated with EC risk, but the majority of the publications reported statistically significant increased risks associated with higher temperature of use. For maté, individual studies and the combined analyses showed increased risk of EC associated with both amount consumed and with temperature of drinking, and these two seemed to be independent risk factors. For other hot foods and drinks, the majority of studies showed higher risk of EC associated with higher temperature of use.
There are several limitations to making definitive conclusions about the association of amount or temperature of these drinks with EC risk. Some of these limitations are due to the design of the published studies (retrospective nature of the data, subjective questions, incomplete questionnaires, and lack of information on histologic type of EC) and others are due to incomplete analysis or reporting of the data. The large majority of the reports were based on retrospective case-controls studies, so the data might have been subject to interviewer bias or recall bias. This is further complicated by asking subjective questions, such as “how hot do you drink your tea?”, which can be particularly prone to such biases. To our knowledge, very few published studies have actually measured the actual temperature of tea, coffee, or maté drinking (reviewed in ref 22). Obtaining data on amount or frequency of drinking per day, total duration of drinking, sip size (or an indicator of this), and temperature of drinking are important. Unfortunately, many of the published studies did not collect data on several of these factors or did not report the results; studying the effect of hot temperature drinks was not the main aim of most of these studies. Furthermore, few studies adjusted the results of drinking temperature for amount consumed and vice versa, and many studies failed to adjust the results for other confounders. Also, many studies combined the results for several types of beverages (e.g., tea and coffee), which made it difficult to look at effects of these drinks separately; this problem was more prominent for black and green tea use. A number of studies reported that the results were not significant, but provided no counts or ORs (95% CIs). Such incomplete reporting prohibits use of the results in future meta-analyses. There is a large body of evidence suggesting that the risk factors for ESCC and EAC may be different. For example, there is strong evidence for a positive dose-response association between body mass index and risk of EAC,100 whereas several studies have reported an inverse association between body mass index and risk of ESCC.99 Nevertheless, few studies reported the results for ESCC and EAC separately.
Because of large heterogeneity in design and reporting, and also incomplete reporting in several studies, we conducted a systematic review but avoided formal combination of the results as a meta-analysis. However, many of the limitations mentioned above can be addressed in future studies. Using a standard questionnaire across studies would help in collecting uniform data. Actual measurement of tea temperature is already being conducted in a cohort study in Iran,22,101 where very high rates of ESCC are seen.102,103 In this study, two simultaneous cups of tea are poured; one is given to the study subject and a thermometer is put in the second cup.101 At intervals of 5°C (75°C, 70°C, 65°C, …) the subject is asked to sip the tea and tell the interviewer whether this is the usual temperature at which he/she drinks tea. This method for measuring tea temperature had shown a very good repeatability 101 and can be used in future studies, especially in areas with very high risk of EC. Measurement of relevant metabolites in biological samples might be helpful to validate the self-reported data on amount of consumed beverages.
Thermal injury may cause EC via both direct and indirect pathways. Inflammatory processes associated with chronic irritation of the esophageal mucosa by local hyperthermia might stimulate the endogenous formation of reactive nitrogen species, and subsequently, nitrosamines.104 This hypothesis is supported by high rates of somatic G > A transitions in CpG dinucleotides of the TP53 gene in ESCC tumor samples from areas in which drinking hot beverages is considered an important risk factor for ESCC;105–108 these mutations may indicate increased nitric oxide synthase activity in tumors.109 Thermal injury can also impair the barrier function of the esophageal epithelium, which may increase the risk of damage from exposure to intra-luminal carcinogens.110 An association between hot drinks and precancerous lesion of the esophagus has also been reported.111,112 Nevertheless, further prospective studies are indicated to investigate the association between high-temperature beverage or food consumption and risk of EC.
Chemical composition of tea, coffee, and maté has been reviewed in detail elsewhere.21 Some constituents of tea, coffee, and maté may have anti-carcinogenic properties; for example, flavonoids and caffeine show antioxidant activities.12,13,113 Composition of the beverages may change during production procedures; for example, in production of black tea and coffee, fermentation of tea leaves reduces a large percentage of some flavonoids,12,13 and severe roasting of coffee beans can considerably reduce their total cholorogenic acid content.21 Furthermore, black tea and maté may acquire some potentially carcinogenic contaminants, such as polycyclic aromatic hydrocarbons (PAH) and mycotoxins, when being processed;114,115 high levels of PAH exposure has been reported among black tea and maté drinkers.116,117 Both black and green tea drinking may increase plasma antioxidant activity in humans.118 On the other hand, in a clinical trial in Linxian and Huixian, China, decaffeinated green tea was not shown to have beneficial effects in alleviating esophageal precancerous lesions and abnormal cell proliferation patterns after 11 years of follow-up.119 Other hot foods and drinks, such as foods containing processed meat and preserved fish,120 may potentially have carcinogenic chemical constituents. However, most studies used in this review compared the intake of the same food in higher versus lower temperatures. Therefore, unless higher temperature results in further formation or release of carcinogens, the results should not be confounded by chemical constituents, and any association should be attributed to thermal injury.
Although the number of studies that reported inverse associations between amount of tea or coffee consumed is higher than the number of studies that showed positive associations, the overall results are mixed. Despite cancer preventive activity of tea in experimental studies, it is not clear why epidemiological studies have not consistently shown an inverse association between tea drinking and risk of EC. Furthermore, all of the epidemiological studies that showed a statistically significant inverse association between tea drinking and risk of EC were case-control studies. In case-control studies, a possible reduction in tea intake by EC cases following their symptoms might lead to under-reporting of past tea consumption, and subsequently, resulting in spurious inverse associations. Tea and coffee contain several compounds other than flavonoids21 and may have some contaminants, which their interactions and their complex metabolisms might alter the protective effect of the individual compounds.17 It has also been suggested that flavonoids, or other anti-oxidants, in high doses may act as pro-oxidant that can generate free radicals, which may lead to DNA damage and finally irreversible pre-neoplastic lesions (reviewed in refs. 8,121).
In conclusion, there was little evidence for an association between EC risk and amount of tea or coffee consumed but the results suggest an increased risk of EC associated with higher drinking temperature. Amount, duration, and temperature of maté intake were all associated with higher EC risk, but number of the studies that investigated these associations was limited. For other hot foods and drinks, there was some evidence showing increased risk with higher temperature. Overall, the available results strongly suggest that high-temperature beverage drinking increases the risk of EC. Future studies will require standardized strategies that allow for combining data, and results should be reported by histological subtypes of EC.
This study was supported in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health.