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, a number of more recent experimental studies in animals have reported cancer preventive activities for these beverages (reviewed in refs. ). 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, but coffee drinking was shown to be inversely associated with risk of liver cancer.

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. 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.

Discussion

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 ). 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, whereas several studies have reported an inverse association between body mass index and risk of ESCC. 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,where very high rates of ESCC are seen.

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. 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  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. This hypothesis is supported by high rates of somatic G > A transitions in CpG dinucleotides of the TP53gene in ESCC tumor samples from areas in which drinking hot beverages is considered an important risk factor for ESCC; these mutations may indicate increased nitric oxide synthase activity in tumors. 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. An association between hot drinks and precancerous lesion of the esophagus has also been reported. 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. Some constituents of tea, coffee, and maté may have anti-carcinogenic properties; for example, flavonoids and caffeine show antioxidant activities. 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, and severe roasting of coffee beans can considerably reduce their total cholorogenic acid content. Furthermore, black tea and maté may acquire some potentially carcinogenic contaminants, such as polycyclic aromatic hydrocarbons (PAH) and mycotoxins, when being processed; high levels of PAH exposure has been reported among black tea and maté drinkers. Both black and green tea drinking may increase plasma antioxidant activity in humans. 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. Other hot foods and drinks, such as foods containing processed meat and preserved fish, 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 flavonoids and may have some contaminants, which their interactions and their complex metabolisms might alter the protective effect of the individual compounds. 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. ).

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.