Mate ´ Consumption and the Risk of Squamous Cell Esophageal Cancer in Uruguay 1 Vikash Sewram, Eduardo De Stefani, Paul Brennan, and Paolo Boffetta 2 Promec Unit, Medical Research Council, Tygerberg, South Africa [V. S.]; International Agency for Research on Cancer, Lyon, France [V. S., P. B., P. B.]; and Registro Nacional de Cancer, Montevideo, Uruguay [E. D. S.] Abstract A retrospective hospital-based case-control study was carried out at the Oncology Institute of Montevideo, Uruguay, to investigate the role of mate ´ consumption in esophageal cancer risk. The study included 344 cases with squamous cell carcinoma of the esophagus and 469 controls recruited between January 1988 and August 2000. Mate ´ consumption was significantly associated with an increased risk of developing esophageal cancer and showed a clear dose response, with a relative risk of 2.84 [95% confidence interval (CI), 1.41–5.73] for those drinking more than 1 liter/day of mate ´ as compared with nondrinkers. Subjects who self-reported drinking mate ´ at a very hot temperature had an almost 2-fold increase in risk [odds ratio (OR), 1.87; 95% CI, 1.17–3.00] compared with those drinking warm to hot mate ´, after adjusting for cumulative consumption of mate ´. Mate ´ amount and temperature were observed to have independent effects and, although no departure from multiplicativity was observed between the two covariates, those drinking more than 1 liter/day of mate ´ at a very hot temperature had a 3-fold increase in risk (OR, 2.95; 95% CI, 1.30 – 6.74) compared with those drinking less than 0.5 liter/day of mate ´ at a warm to hot temperature. Subjects with high cumulative exposure to mate ´ in the presence of low alcohol and tobacco exposures presented a lower-risk estimate (OR, 1.52; 95% CI, 0.88 –2.62), whereas those with high cumulative exposures to mate ´, alcohol, and tobacco presented a 7-fold increase in esophageal cancer risk (OR, 7.10; 95% CI, 3.75–13.46). The population- attributable fraction as a result of mate ´ consumption was calculated to be 53%, of which the sole effect of amount and temperature was 14.8 and 12.6% respectively, and 14.9% was attributable to high mate ´ consumption at high temperature. Introduction Esophageal cancer is a malignancy that exhibits a wide diver- sity in geographical incidence and mortality worldwide (1). Areas with high incidence rates include parts of South America, southeastern Africa, and the so-called esophageal cancer belt in Asia, which stretches from the Caspian provinces of Iran through the central Asian republics to northern China (2). There is a geographical cluster of high-incidence areas in South America, which includes northeastern Argentina, southern Bra- zil, Paraguay, and Uruguay (1). Data from the Cancer Registry at the Oncology Institute of Montevideo, Uruguay, have revealed age-standardized inci- dence rates of esophageal cancer of 11.9 and 3.4 per 100,000 for men and women, respectively (3). However, in the north- eastern region bordering with Brazil, the age-standardized in- cidence rates are reported to be 55.8 and 14.7 per 100,000 for men and women, respectively (4). The most important histo- logical type in this region is squamous cell carcinoma (5). Results from studies conducted in Uruguay and Brazil have identified alcohol drinking and tobacco smoking as important risk factors for esophageal cancer (6, 7). However, risk is further aggravated by diets deficient in fruits and vegetables (8, 9), by high consumption of red meat (4), and by other envi- ronmental and lifestyle exposures (10, 11). In addition, factors producing chronic injury to the esophagus, such as rough foods and hot beverages, can contribute to the burden of esophageal cancer by increasing susceptibility to carcinogens (7). The drinking of mate ´, a tea-like infusion of the herb Ilex paraguariensis (Aquifoliaceae) which is cultivated on a com- mercial scale, is particularly prevalent in southern Brazil and in Uruguay. A striking ecological correlation was observed be- tween the distribution of mate ´ drinking and the high rates of esophageal cancer, leading to the hypothesis that mate ´ drinking may be an etiological factor for esophageal cancer (12). Studies in Brazil (6), Uruguay (7, 13) and Argentina (14), however, have yielded inconsistent results. In a pooled analysis of data from five studies conducted in Argentina, Brazil, Paraguay, and Uruguay (15, 16), the main risk factors for esophageal cancer were tobacco and alcohol consumption. However, after adjust- ment for the strong effects of these exposures, heavy mate ´ drinking (1 liter/day) and self-reported very hot mate ´ drinking were significant risk factors in men and women. To elucidate the relationship between mate ´ drinking and esophageal cancer risk, a retrospective hospital-based case- control study was undertaken in Uruguay to investigate the role of mate ´ consumption, and in particular, the effect of quantity and temperature, in the risk of developing esophageal cancer. Material and Methods Selection of Cases. At the Oncology Institute of Montevideo, all patients who were newly diagnosed with histopathologically confirmed squamous cell carcinoma of the esophagus between January 1988 and August 2000, and who were ages 35– 85 Received 7/18/02; revised 2/5/03; accepted 3/4/03. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 Supported by grants from the Comisio ´n Honoraria de Lucha contra el Ca ´ncer (Montevideo, Uruguay) and the IARC. Dr. V. Sewram worked on this study under the tenure of a Technical Transfer Award from the IARC. 2 To whom requests for reprints should be addressed, at Unit of Environmental Cancer Epidemiology, International Agency for Research on Cancer, 150 cours Albert-Thomas, 69008 Lyon, France. Phone: 33-4-72738441; Fax: 33-4-72738320; E-mail: boffetta@iarc.fr. 508 Vol. 12, 508 –513, June 2003 Cancer Epidemiology, Biomarkers & Prevention Research. on October 5, 2021. © 2003 American Association for Cancer cebp.aacrjournals.org Downloaded from