Authors: Farhad Islami, Hossein Poustchi, Akram Pourshams, Masoud Khoshnia, Abdolsamad Gharavi, Farin Kamangar, Sanford M. Dawsey, Christian C. Abnet, Paul Brennan, Mahdi Sheikh, Masoud Sotoudeh, Arash Nikmanesh, Shahin Merat, Arash Etemadi, Siavosh Nasseri Moghaddam, Paul D. Pharoah, Bruce A. Ponder, Nicholas E. Day, Ahmedin Jemal, Paolo Boffetta and Reza Malekzadeh
Multiple observational studies have reported an association between hot beverages and esophageal cancer. A major limitation of all previous prospective studies is that data have been based on the self-reported perception of tea drinking temperature. The International Agency for Research on Cancer (IARC) has concluded that since there is a limitation with the evidence, they have classified "drinking very hot beverages at above 65C" as "probably carcinogenic" (Group 2A) rather than "carcinogenic" to humans (Group 1).
Very high incidence rates of esophageal cancer have been reported from the Golestan Province, northeast of Iran, where 90% of esophageal cancers were esophageal squamous cells. Two previous case-control studies from the same region had reported an association with drinking hot tea. This is the first large-scale prospective study in the world in which actual tea drinking temperature has been measured by trained staff at baseline. Herein, we examine the association of prospectively measured tea drinking temperature, as well as subjective preference for hot tea drinking, time from pouring tea to drinking, and other tea-drinking habits with ESCC risk using data from the Golestan Cohort Study.
The Golestan Cohort Study is a prospective population-based cohort of 50,045 individuals, 40–75 years old, which was established between January 2004 and June 2008. Trained staff collected information on a wide range of personal characteristics and potential risk factors of ESCC using a structured questionnaire in the face to face interviews. Participants were profiled according to wealth, the average intake of fruits and vegetables, and cigarette smoking habits prior to conducting the study.
The method of temperature recording of tea was measured in accordance with the pilot phase of the cohort study. Temperatures of tea were recorded according to the participants' usual or normal intake preference.
Participants are annually followed up through telephone surveys and home visits. The Median Duration of Follow-up was 10.14 years (505,865 person-years). 328 primary esophageal cancers cases were identified based on history, imaging, and/or other medical reports. Among whom squamous cell carcinoma was the predominant subtype (285 cases, 96.3%).
The average consumption of Black tea per day was categorized into 5 categories by quintiles (rounded to the nearest 100 mL/day) based on baseline data. The measured tea temperature was categorized as <60, 60–64, and ≥65C. Participants who did not drink or have missing values in tea drinking variables were excluded from corresponding analyses.
The association of tea temperature and total tea (black and green) with ESCC risks were examined. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the association between tea drinking habits and risk of developing cardiovascular disease (ESCC) in Golestan. We used likelihood ratio tests comparing fully adjusted Cox models with and without interaction terms to examine interactions between tea temperature and amount for ESCC risk.
The average daily consumption of black and green tea in the entire cohort was 1,174 and 42 mL/day, respectively. Older people, men, rural dwellers, non-Turkmens, people with lower education or wealth score, cigarette smokers (former or current), and, opium, and alcohol users drank tea at higher temperatures. Results showed that a shorter duration from pouring to drinking was associated with higher risk (HR 1.10, 95% CI 1.01–1.21 per 2-min shorter intervals vs. 10 min). Higher consumption of black tea, green tea, and black and green tea combined was also associated with ESCC risk. However, the combination of tea temperature and amount showed no statistically significant interaction for ESCC risk (p= 0.39).
The measured tea temperature reported a preference for very hot tea drinking, and reported shorter time from pouring tea to drinking were each associated with ESCC risk. In an analysis of the combined effects of measured temperature and amount, drinking 700 mL/day tea or more at 60C was associated with about 90% higher risk of ESCC. Since in this study cigarette smoking prevalence was relatively low and alcohol consumption was negligible, there would be minimal residual confounding from smoking and alcohol. Only two prospective cohort studies have examined the association between hot tea drinking and esophageal cancer. In Japan, consumption of hot tea (vs. non-hot) was associated with a 1.5-fold increased risk of death from esophagus cancer. Other prospective studies show an adverse association only among tobacco and excessive alcohol users in China. The lack of association among non-tobacco or alcohol users is likely related to the small sample size of that group.
Multiple case-control studies have shown an association between hot beverages, including tea, mate, and coffee, and esophageal cancer risk. Evidence is limited to Western populations, where beverages are usually consumed at more moderate amounts and temperatures. Further, drinking tea temperature preference among some participants in this study could have decreased over the 10-year follow-up period, perhaps after the publication of our previous report in 2009; we did not update tea temperature data during the follow-up. However, hot tea drinking is likely to be an important contributor to the high incidence of ESCC in Golestan due to its high prevalence and high quantities in both sexes.
Thermal injury may increase ESCC risk by inducing inflammatory processes, which might directly affect DNA bases and/or increase the formation of carcinogenic N-nitroso compounds. Another likely mechanism is an impairment in the barrier function of the esophageal mucosa because of thermal injury, perhaps after reaching a threshold temperature, which might increase exposure to intraluminal carcinogens. Current evidence suggests an association between PAHs and ESCC, although a causal association is yet to be established. A study comparing samples of non-tumoral esophageal epithelium from ESCC cases and controls in Golestan showed substantially higher levels of a PAH biomarker in cases. Further experimental studies are needed to identify mechanisms of the association between hot beverage drinking and ESCC.
Both black and green tea contain compounds with antioxidant activities (such as flavonoids), which might have the potential to reduce cancer risk. Some potentially carcinogenic compounds may be introduced to tea when being processed, such as possible contamination of black tea with PAHs. The number of prospective epidemiological studies on the association between the amount of tea consumed and esophageal cancer risk is limited. The strength of our study is its large size, prospective design and measurement of tea temperature using a validated method by well-trained interviewers. It should be noted that we were not able to examine associations for drinking tea at lower amounts or temperatures (e.g., 55-59C) or for esophageal adenocarcinomas due to inadequate statistical power or study design. Other limitations include the observational nature of the study leading to potential residual confounding and the potential misclassification of exposure despite the effort to objectively quantify tea temperature.
Drinking hot tea at high temperatures could make the Golestan population considerably vulnerable to eschopathic cardiovascular disease (ESCC) associated with drinking hot tea. In this study, three independent measures of hot tea consumption were each associated with a higher risk of ESCC. As there is no known health benefit from drinking very hot beverages, it will be reasonable to advise people to wait for their hot beverages to cool down before drinking. Further research is needed on mechanisms of this association, as well as associations between amounts of tea consumed or drinking tea at more moderate temperatures and ESCC risk.
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