Greenteahaus:  The Green Tea Reference Library

Epidemiological and clinical studies on the relationship between cancer risk and the consumption of green tea, its dose and its source

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1 Green tea: cancer preventive beverage and/or drug. Cancer Lett 2002;188:9-13.
2 Cancer prevention with green tea and monitoring by a new biomarker, hnRNP B1. Mutat Res 2001;480-481:299-304.
3 Reduced risk of esophageal cancer associated with green tea consumption. J Natl Cancer Inst 1994 Jun 1;86(11):855-8.
4 A case control study of cancer of the pancreas Gan No Rinsho 1990 Feb;Spec No:344-50 [Article in Japanese]
5 Prostate cancer chemoprevention by green tea. Semin Urol Oncol. 1999 May;17(2):70-6.
6 Cancer-preventive effects of drinking green tea among a Japanese population. Prev Med 1997 Nov-Dec;26(6):769-775.
7 Tea and coffee consumption and the risk of digestive tract cancers: data from a comparative case-referent study in Japan. Cancer Causes Control. 1998 Mar;9(2):209-16. of intake and have no clear explanation for site-specificity.
8 Regular 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 Lett 2001;167:175-82.
9 Green tea consumption and the risk of pancreatic and colorectal cancers. Int J Cancer 1997 Jan 27;70(3):255-8.
10 The influence of cigarette smoking, alcohol, and green tea consumption on the risk of carcinoma of the cardia and distal stomach in Shanghai, China. Cancer. 1996 Jun 15;77(12):2449-57.
11 Chemoprevention of bladder cancer. Urol Clin North Am 2002 ;29:157-68.
12 A comparative case-control study of colorectal cancer and adenoma. Jpn J Cancer Res. 1990;81(11):1101-8.
13 A case-control study of gastric cancer and diet in northern Kyushu, Japan. Jpn J Cancer Res. 1988 Oct;79(10):1067-74.
14 Physical activity, dietary habits and adenomatous polyps of the sigmoid colon: a study of self-defense officials in Japan. J Clin Epidemiol 1991;44(11):1255-61.
15 Green tea and gastric cancer in Japan. N Engl J Med 2001;344:1867-8.
16 Can teatime increase one's lifetime? Ageing Res Rev 2003;2:1-10.
17 Preventive effects of drinking green tea on cancer and cardiovascular disease: epidemiological evidence for multiple targeting prevention. BioFactors 2000;13(1-4):49-54.
18 Influence of drinking green tea on breast cancer malignancy among Japanese patients. Jpn J Cancer Res. 1998 Mar;89(3):254-61.
19 Protection against cancer risk by Japanese green tea (abstract) Prev Med 1992; 21: 332.
20 Case-control study of urinary bladder cancer in metropolitan Nagoya. Natl Cancer Inst Monogr. 1985 Dec;69:229-34.
21 Tea consumption and lung cancer risk: a case-control study in Okinawa, Japan. Jpn J Cancer Res. 1995 Nov;86(11):1027-34.
22 Protective effect of green tea on the risks of chronic gastritis and stomach cancer. Int J Cancer 2001;92:600-4.
23 Green tea consumption and chronic atrophic gastritis: a cross-sectional study in a green tea production village. J Epidemiol 2000;10:310-6.
24 Prognostic significance of selected lifestyle factors in urinary bladder cancer. Jpn J Cancer Res 1993 Dec;84(12):1223-9.
25 A case-control study on the dietary risk factors of upper digestive tract cancer. Zhonghua Liu Xing Bing Xue Za Zhi. 1999 Apr;20(2):95-7.
26 Green tea and risk of breast cancer in Asian Americans. Int J Cancer. 2003;106(4):574-9.
27 Diet and gastric cancer: a casecontrol study in Fujian Province, China. World J Gastroenterol. 1998 Dec;4(6):516-518.
28 Green-tea consumption and risk of stomach cancer: a population-based case-control study in Shanghai, China. Cancer Causes Control. 1995 Nov;6(6):532-8.
29 Risk factors for stomach cancer: a population-based case-control study in Shanghai. Cancer Causes Control. 1991 May;2(3):169-74.
30 Tea consumption and ovarian cancer risk: a case-control study in China. Cancer Epidemiol Biomarkers Prev 2002;11:713-8.
31 A population-based case-control study of lung cancer and green tea consumption among women living in Shanghai, China. Epidemiology. 2001 Nov;12(6):695-700.
32 Protective effect of green tea against prostate cancer: a case-control study in southeast China. Int J Cancer. 2004 Jan 1;108(1):130-5.

Abstracts
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1 Fujiki H, Suganuma M, Imai K, Nakachi K. Green tea: cancer preventive beverage and/or drug. Cancer Lett 2002;188:9-13.

Green tea and (-)-epigallocatechin gallate (EGCG) are now acknowledged cancer preventives in Japan and has made it possible for us to establish the concept of a cancer preventive beverage. For the general population, we recommend 10 cups of green tea daily supplemented with green tea tablets. For cancer patients following treatment, we here present new evidence that green tea and a cancer preventive drug, sulindac, have synergistic preventive effects. An approach to develop green tea capsules as a cancer preventive drug in the US is discussed, aiming at taking full advantage of this cancer preventive beverage.
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2 Fujiki H, Suganuma M, Okabe S, Sueoka E, Sueoka N, Fujimoto N, Goto Y, Matsuyama S, Imai K, Nakachi K. Cancer prevention with green tea and monitoring by a new biomarker, hnRNP B1. Mutat Res 2001;480-481:299-304.

The study of green tea polyphenols as a cancer preventative is approaching a new era, with significant results accumulating rapidly. This paper briefly reviews four topics related to mechanisms of action of tea polyphenols: (I) identification of the genes commonly affected by EGCG, as demonstrated by Clontech's Atlas cDNA Expression Array; (II) the significance of heterogeneous nuclear ribonucleoprotein B1 (hnRNP B1) as a new biomarker for early detection of lung cancer, and inhibition of its expression by EGCG; (III) the synergistic or additive effects of EGCG with the cancer preventive agents, sulindac and tamoxifen, on induction of apoptosis in PC-9 cells and on inhibition of intestinal tumor development in multiple intestinal neoplasia (Min) mice; (IV) the results of a 10 year prospective cohort study demonstrating the effectiveness of daily consumption of green tea in preventing cancer, and a prototype study for developing green tea beverage as cancer preventive.
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3 Gao YT, McLaughlin JK, Blot WJ, Ji BT, Dai Q, Fraumeni JF Jr. Reduced risk of esophageal cancer associated with green tea consumption. J Natl Cancer Inst 1994 Jun 1;86(11):855-8.

BACKGROUND: Studies in laboratory animals have suggested inhibitory effects of green tea on the induction of some cancers, notably, esophageal cancer. However, only a few epidemiologic studies have evaluated green tea as a potential inhibitor of human esophageal cancer.
PURPOSE: Our purpose was to evaluate the relationship between green tea consumption and the risk of esophageal cancer.
METHODS: This esophageal cancer study was part of a larger multicenter, case-control study that included three other gastrointestinal sites (pancreas, colon, and rectum). Medical records of patients aged 30-74 years old who were diagnosed with esophageal cancer from October 1, 1990, through January 31, 1993, were identified from the Shanghai Cancer Registry, which covers 6.8 million people in the urban area of Shanghai, People's Republic of China. During the ascertainment period, records of 1016 eligible cases of esophageal cancer were identified. Control subject records were selected by frequency matching in accordance with the age-sex distribution of the four gastrointestinal cancers ascertained by the cancer registry during 1986-1987. Patient interviews were then conducted using a structured, standardized questionnaire to obtain information on demographic characteristics, residential history, height and weight, diet, smoking, alcohol and tea drinking, medical history, family history of cancer, occupation, physical activity, and reproductive history.
RESULTS: Of the 902 patients interviewed, 734 (81.4%) had their disease pathologically confirmed. There were 1552 control subjects interviewed, including 240 alternates. All analyses of tea effects were conducted separately among men and women and all were adjusted for age. After further adjustment for other known confounders, a protective effect of green tea drinking on esophageal cancer was observed among women (odds ratio [OR] = 0.50; 95% confidence interval [CI] = 0.30-0.83), and this risk decreased (P for trend < or = .01) as tea consumption increased. Among men, the ORs were also below 1.00, although not statistically significant. ORs for green tea intake were estimated among those persons who neither smoked nor drank alcohol. In this subset, statistically significant decreases in risk among tea drinkers were observed for both men (OR = 0.43; 95% CI = 0.22-0.86; P for trend = .05) and women (OR = 0.40; 95% CI = 0.20-0.77; P for trend < .001).
CONCLUSIONS: This population-based, case-control study of esophageal cancer in urban Shanghai suggests a protective effect of green tea consumption. Although these findings are consistent with studies in laboratory animals, indicating that green tea can inhibit esophageal carcinogenesis, further investigations are definitely needed.
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4 Goto R, Masuoka H, Yoshida K, Mori M, Miyake H. A case control study of cancer of the pancreas Gan No Rinsho 1990 Feb;Spec No:344-50 [Article in Japanese]

We report the findings of a case-control study of cancer of the pancreas, which was conducted in Hokkaido Prefecture. Seventy-one patients with pancreatic cancer were matched on sex and age (+/- 3 years) to 142 community-based controls. The latter had telephone interviews. We questioned all subjects about demographic factors, diet, beverage consumption, and medical and surgical history. Significantly decreased risks were associated with consumption of raw vegetables and green tea. The risk increased significantly with consumption of the fat of meat, boiled fish, coffee, black tea and alcoholic beverages.
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5 Gupta S, Ahmad N, Mukhtar H. Prostate cancer chemoprevention by green tea. Semin Urol Oncol. 1999 May;17(2):70-6.

Prostate cancer (PCA) is one of the most invasive cancers and the second leading cause of cancer-related deaths among males in the United States. According to an estimate, 1 of every 11 American men will eventually develop PCA. One way to reduce the occurrence of cancer is through chemoprevention. PCA represents an excellent candidate disease for chemoprevention because it is typically diagnosed in men over 50 years of age, and therefore even a modest delay in neoplastic development achieved through pharmacological or nutritional intervention could result in a substantial reduction in the incidence of clinically detectable disease. The ideal agent(s) suitable for chemoprevention of PCA should be the one(s) that has proven efficacy in the laboratory experiments on one hand, and also possesses proven epidemiological basis on the other hand. This review attempts to address the issue of possible uses of tea, especially green tea, for the prevention of PCA. We are providing the experimental as well as the epidemiological basis for this possibility. Many laboratory experiments conducted in cell culture systems and in animal models have shown the usefulness of green tea, and the polyphenols present therein, against PCA. The epidemiological basis for this possibility is twofold. First, some epidemiological observations have suggested that people who consume tea regularly have a lower risk of PCA-related deaths. Second, the incidence of PCA in China, a population that consumes green tea on a regular basis, is lowest in the world.
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6 Imai K, Suga K, Nakachi K. Cancer-preventive effects of drinking green tea among a Japanese population. Prev Med 1997 Nov-Dec;26(6):769-775.

BACKGROUND: Laboratory studies have revealed the cancer preventive effects of green tea, so the association between green tea consumption and cancer was examined in a human population.
METHODS: The association between green tea consumption and cancer incidence was studied in our prospective cohort study of a Japanese population. We surveyed 8,552 individuals over 40 years of age living in a town in Saitama prefecture on their living habits, including daily consumption of green tea. During the 9 years of follow-up study (71,248.5 person-years), we identified a total of 384 cases of cancer in all sites.
RESULTS: We found a negative association between green tea consumption and cancer incidence, especially among females drinking more than 10 cups a day. The slowdown in increase of cancer incidence with age observed among females who consumed more than 10 cups a day is consistent with the finding that increased consumption of green tea is associated with later onset of cancer. Age-standardized average annual incidence rate was significantly lower among females who consumed large amounts of green tea. Relative risk (RR) of cancer incidence was also lower among both females (RR = 0.57, 95% CI = 0.33-0.98) and males (RR = 0.68, 95% CI = 0.39-1.21) in groups with the highest consumption, although the preventive effects did not achieve statistical significance among males, even when stratified by smoking and adjusted for alcohol and dietary variables.
CONCLUSION: Our epidemiological study showed that green tea has a potentially preventive effect against cancer among humans.
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7 Inoue M, Tajima K, Hirose K, Hamajima N, Takezaki T, Kuroishi T, Tominaga S. Tea and coffee consumption and the risk of digestive tract cancers: data from a comparative case-referent study in Japan. Cancer Causes Control. 1998 Mar;9(2):209-16.

OBJECTIVES: The purpose of this study was to examine the hypothesis that tea and coffee consumption have a protective effect against development of digestive tract cancers.
METHODS: A comparative case-referent study was conducted using Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC) data from 1990 to 1995 in Nagoya, Japan. This study comprised 1,706 histologically diagnosed cases of digestive tract cancers (185 esophagus, 893 stomach, 362 colon, 266 rectum) and a total of 21,128 non-cancer outpatients aged 40 years and over. Logistic regression was used to analyze the data, adjusting for gender; age; year and season at hospital-visit; habitual smoking and alcohol drinking; regular physical exercise; fruit, rice, and beef intake; and beverage intake.
RESULTS: The odds ratio (OR) of stomach cancer decreased to 0.69 (95 percent confidence interval [CI] = 0.48-1.00) with high intake of green tea (seven cups or more per day). A decreased risk was also observed for rectal cancer with three cups or more daily intake of coffee (OR = 0.46, CI = 0.26-0.81).
CONCLUSIONS: The results suggest the potential for protective effect against site-specific digestive tract cancer by consumption of green tea and coffee, although most associations are limited only to the upper category of intake and have no clear explanation for site-specificity.
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8 Inoue M, Tajima K, Mizutani M, Iwata H, Iwase T, Miura S, Hirose K, Hamajima N, Tominaga S. Regular 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 Lett 2001;167:175-82.

This study was conducted to examine the association between regular green tea consumption prior to diagnosis and subsequent risk of breast cancer recurrence. The Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC) was started in 1988, in which information on lifestyle has routinely been collected from all first-visit outpatients by questionnaire. A total of 1160 new surgical cases of female invasive breast cancers with HERPACC information diagnosed between June 1990 and August 1998 were followed up through December 1999, and the risk (hazard ratio: HR) of recurrence was assessed with reference to daily green tea consumption using a Cox proportional hazard model. During 5264 person-years of follow-up, 133 subjects (12%) were documented to suffer recurrence of breast cancer. A decreased HR for recurrence adjusted for stage was observed with consumption of three or more daily cups of green tea (HR=0.69, 95% confidence interval (95%CI)=0.47-1.00). Particularly in stage I, the HR was decreased statistically significantly (HR=0.43, 95%CI=0.22-0.84). A similar tendency was observed for stage II subjects, but was not present among more advanced stages. Although careful interpretation is needed, these results suggest the possibility that regular green tea consumption may be preventive against recurrence of breast cancer in early stage cases.
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9 Ji BT, Chow WH, Hsing AW, McLaughlin JK, Dai Q, Gao YT, Blot WJ, Fraumeni JF Jr. Green tea consumption and the risk of pancreatic and colorectal cancers. Int J Cancer 1997 Jan 27;70(3):255-8.

The effect of green tea drinking in reducing human cancer risk is unclear, though a protective effect has been reported in numerous animal studies and several epidemiologic investigations. Herein the hypothesis that green tea consumption may reduce the risk of cancers of the colon, rectum and pancreas is examined in a large population-based case-control study conducted in Shanghai, China. Newly diagnosed cancer cases (931 colon, 884 rectum and 451 pancreas) during 1990-1993 among residents 30-74 years of age were included. Controls (n = 1,552) were selected among Shanghai residents and frequency-matched to cases by gender and age. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) of each cancer associated with green tea consumption were derived after adjustment for age, income, education and cigarette smoking. Additional adjustment for dietary items and body size was found to have minimal impact. An inverse association with each cancer was observed with increasing amount of green tea consumption, with the strongest trends for rectal and pancreatic cancers. For men, compared with non-regular tea drinkers, ORs among those in the highest tea consumption category (> or = 300 g/month) were 0.82 for colon cancer, 0.72 for rectal cancer and 0.63 for pancreatic cancer, with p values for trend being 0.38, 0.04 and 0.04, respectively. For women, the respective ORs for the highest consumption category (> or = 200 g/month) were 0.67, 0.57 and 0.53, with the respective p values for trend being 0.07, 0.001 and 0.008. Our findings provide further evidence that green tea drinking may lower the risk of colorectal and pancreatic cancers.
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10 Ji BT, Chow WH, Yang G, McLaughlin JK, Gao RN, Zheng W, Shu XO, Jin F, Fraumeni JF Jr, Gao YT. The influence of cigarette smoking, alcohol, and green tea consumption on the risk of carcinoma of the cardia and distal stomach in Shanghai, China. Cancer. 1996 Jun 15;77(12):2449-57.

BACKGROUND: The divergent incidence patterns of gastric cardia and distal stomach cancer may suggest different etiologies. This study examined the role of cigarette smoking, alcohol drinking, and green tea consumption as risk factors for carcinoma by anatomic subsite of stomach.
METHODS: Newly-diagnosed stomach carcinoma patients (n = 1124) and frequency-matched population controls (n = 1451) were interviewed in person. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models.
RESULTS: Excess risks associated with cigarette smoking and alcohol consumption were observed largely among men. The adjusted ORs for all stomach cancer combined were 1.35 (CI: 1.06-1.71) for current smokers, and 1.26 (CI: 0.86-1.84) for ex-smokers. For tumors of the distal stomach, statistically significant positive dose-response trends were found for the number of cigarettes smoked per day, the duration and pack-years of smoking, and inverse trends for years of stopped smoking. For tumors of the gastric cardia, however, a monotonic association was found only for the number of cigarettes smoked per day (P=0.06). Alcohol consumption was not related to the risk of cardia cancer, while a moderate excess risk of distal stomach cancer (OR: 1.55; CI: 1.07-2.26) was observed among heavy alcohol drinkers. Green tea drinking was inversely associated with risk of stomach cancer arising from either subsite, with ORs of 0.77 (CI: 0.52-1.13) among female heavy drinkers, and 0.76 (CI: 0.55-1.27) among male heavy drinkers.
CONCLUSIONS: Our findings provide further evidence that cigarette smoking and, possibly, alcohol consumption increase the risk of stomach carcinoma, notably of the distal segment. An inverse association with green tea drinking was also observed.
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11 Kamat AM, Lamm DL. Chemoprevention of bladder cancer. Urol Clin North Am 2002 ;29:157-68.

Among the numerous other compounds and dietary substances purported to have chemopreventive effect, soybeans, garlic, and green tea stand out as having the greatest promise and can freely be recommended to patients. There is a mistaken notion that simply because an agent is naturally occurring, it cannot be as beneficial as taking a substance synthesized in the laboratory. Encouraging patients to follow an essentially healthy food habit lifestyle will be a significant contribution in the fight against cancer.
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12 Kato I, Tominaga S, Matsuura A, Yoshii Y, Shirai M, Kobayashi S. A comparative case-control study of colorectal cancer and adenoma. Jpn J Cancer Res. 1990;81(11):1101-8.

We conducted a comparative case-control study of colorectal cancer and adenoma involving 221 cases with colorectal cancer, 525 cases with colorectal adenoma and 578 neighborhood controls. Daily vegetables intake was associated with lower risks of distal colon adenoma (relative risks (RR) = 0.59, 95% confidence interval (CI): 0.39-0.89) and rectal cancer (RR = 0.46, 95% CI: 0.25-0.84). Daily beans intake was associated with lower risk of colon adenoma (RR = 0.58, 95% CI: 0.37-0.91 for the proximal colon and RR = 0.63, 95% CI: 0.45-0.88 for the distal colon) and daily intake of seaweeds was associated with lower risk of rectal cancer (RR = 0.42, 95% CI: 0.22-0.82). Daily intake of fish and shellfish also showed an inverse association with the risk of colon adenoma (RR = 0.67, 95% CI: 0.45-0.99 for the proximal colon and RR = 0.70, 0.52-0.94 for the distal colon). Generally, intakes of animal or vegetable fat-rich foods, especially meats, were associated with decreases in risks of both adenoma and cancer, though the association of cancer was not statistically significant. Other than dietary factors, daily alcohol drinking was associated with an increased risk of adenoma in the proximal colon (RR = 1.95, 95% CI: 1.15-3.29) and ex-drinkers showed higher risks for colon adenoma and colorectal cancer. Sports or occupational activities and coffee drinking were inversely associated and family history of colorectal cancer was positively associated with the risk of both colorectal adenoma and cancer. Daily intake of hot green tea was inversely associated with the risks of distal colon and rectal adenomas and colon cancer (page 1103).
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13 Kono S, Ikeda M, Tokudome S, Kuratsune M. A case-control study of gastric cancer and diet in northern Kyushu, Japan. Jpn J Cancer Res. 1988 Oct;79(10):1067-74.

A case-control study of gastric cancer was done in a rural area of northern Kyushu, Japan, in relation to dietary habits especially focusing on the relationship with the consumption of broiled fish. The study was based upon 139 cases of newly diagnosed gastric cancer at a single institution, 2,574 hospital controls and 278 controls sampled randomly from the residents of the study area (with sex and year of birth matched). No association was observed between the consumption of broiled fish and gastric cancer risk whether three types of broiled fish (raw fish, dried fish and salted fish) were analyzed separately or as a single category. However, consistently in the comparisons with both sets of controls, the risk of gastric cancer was inversely related with the consumption of fruits and positively associated with cigarette smoking. A decreased risk of gastric cancer was also noted among those with high consumption of green tea (10 or more cups per day).
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14 Kono S, Shinchi K, Ikeda N, Yanai F, Imanishi K. Physical activity, dietary habits and adenomatous polyps of the sigmoid colon: a study of self-defense officials in Japan. J Clin Epidemiol 1991;44(11):1255-61.

Physical activity and dietary habits were compared between 80 men with adenomatous polyps of the sigmoid colon and 1148 men with normal colonoscopy among male retiring self-defense officials. Physical activity as expressed in terms of time spent doing strenuous activities during leisure time was inversely related to the risk of adenomatous polyps. Controlling for rank, smoking, alcohol and body mass index (BMI), odds ratios for the categories of 0, 1-59, 60-119 and greater than or equal to 120 minutes per week were 1.0, 0.88, 0.70 and 0.44, respectively (trend p = 0.015). Among a limited range of foods and beverages, the consumption of rice, green tea and instant coffee tended to be associated with a decreased risk of adenomatous polyps. Although the associations observed with dietary habits still need to be substantiated, the findings on physical activity lend further evidence to the hypothesis that physical activity may be protective in the development of colon cancer.
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15 Kono S. Green tea and gastric cancer in Japan. N Engl J Med 2001;344:1867-8.

Consumption of 10 cups or more green tea per day is necessary to reduce the incidence of stomach cancer. A comment on an article by Tsubono Y, Nishino Y, Komatsu S, Hsieh CC, Kanemura S, Tsuji I, Nakatsuka H, Fukao A, Satoh H, Hisamichi S. Green tea and the risk of gastric cancer in Japan. N Engl J Med 2001;344(9):632-6.
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16 Nakachi K, Eguchi H, Imai K. Can teatime increase one's lifetime? Ageing Res Rev 2003;2:1-10.

Lifestyle-related diseases, including cancer and cardiovascular disease, are also characterized as aging-related diseases, where aging may be the most potent causal factor. In light of this, prevention of lifestyle-related diseases will depend on slowing the aging process and avoiding the clinical appearance of the diseases. Green tea is now accepted as a cancer preventive on the basis of numerous in vitro, in vivo and epidemiological studies. In addition, green tea has also been reported to reduce the risk of cardiovascular disease. The authors found an apparent delay of cancer onset/death and all cause deaths associated with increased consumption of green tea, specifically in ages before 79 in a prospective cohort study of a Japanese population with 13-year follow-up data. This is consistent with analyses of age-specific cancer death rate and cumulative survival, indicating a significant slowing of the increase in cancer death and all cause death with aging. These results indicate that daily consumption of green tea in sufficient amounts will help to prolong life by avoiding pre-mature death, particularly death caused by cancer.
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17 Nakachi K, Matsuyama S, Miyake S, Suganuma M, Imai K. Preventive effects of drinking green tea on cancer and cardiovascular disease: epidemiological evidence for multiple targeting prevention. BioFactors 2000;13(1-4):49-54.

The significance of drinking green tea in prevention of two of the main lifestyle-related diseases, cancer and cardiovascular disease, was demonstrated in terms of a prospective cohort study on a total of 8,552 general residents in Saitama Prefecture, Japan. On the basis of the follow-up study, we revealed decreased relative risk of cancer incidence for those consuming over 10 cups a day, compared with those consuming below 3 cups: 0.54 (95% confidence interval, 0.22-1.34) for men, 0.57 (0.34-0.98) for women, and 0.59 (0.35-0.98) for both sexes. Furthermore, a significant delay in cancer onset was associated with increased consumption of green tea. Next, decreased relative risk of death from cardiovascular disease was 0.58 (0.34-0.99) for men, 0.82 (0.49-1.38) for women, and 0.72 (0.60-1.04) for members of both sexes consuming over 10 cups a day. Finally, we evaluated the life-prolonging effects of drinking green tea on cumulative survival, using the life table. The relative risk for cancers of the colorectum, liver and stomach was most notably reduced.
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18 Nakachi K, Suemasu K, Suga K, Takeo T, Imai K, Higashi Y. Influence of drinking green tea on breast cancer malignancy among Japanese patients. Jpn J Cancer Res. 1998 Mar;89(3):254-61.

Inhibitory effects of green tea on carcinogenesis have been investigated in numerous laboratory studies using (-)-epigallocatechin gallate (EGCG) or crude green tea extract, and there is also some epidemiologic evidence. Further, EGCG has been reported to inhibit the growth of cancer cells, lung metastasis in an animal model, and urokinase activity. In this study, we first examined the association between consumption of green tea prior to clinical cancer onset and various clinical parameters assessed at surgery among 472 patients with stage I, II, and III breast cancer. We found that increased consumption of green tea was closely associated with decreased numbers of axillary lymph node metastases among premenopausal patients with stage I and II breast cancer and with increased expression of progesterone receptor (PgR) and estrogen receptor (ER) among postmenopausal ones. Since these are potential prognostic factors, we then investigated the prognosis of breast cancer with special reference to consumption of green tea, in a follow-up study of these patients. We found that increased consumption of green tea was correlated with decreased recurrence of stage I and II breast cancer (P < 0.05 for crude disease-free survival); the recurrence rate was 16.7 or 24.3% among those consuming > or = 5 cups or < or = 4 cups per day, respectively, in a seven-year follow-up of stage I and II breast cancer, and the relative risk of recurrence was 0.564 (95% confidence interval, 0.350-0.911) after adjustment for other lifestyle factors. However, no improvement in prognosis was observed in stage III breast cancer. Our results indicate that increased consumption of green tea prior to clinical cancer onset is significantly associated with improved prognosis of stage I and II breast cancer, and this association may be related to a modifying effect of green tea on the clinical characteristics of the cancer.
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19 Oguni I, Cheng SJ, Lin PZ, Hara Y. Protection against cancer risk by Japanese green tea (abstract) Prev Med 1992; 21: 332.

Statistics on Japanese people indicated that the cancer mortality rate for both males and females in Shizuoka Prefecture, located in central Japan, is much lower than the average for Japanese people. We further investigated this phenomenon epidemiologically and experimentally. The results were as follows. (a) In the midwest areas of Shizuoka Prefecture, where green tea is the staple product, the standardized mortality ratio (SMR) for cancer of all sites and stomach cancer was much lower than the average ratio for Japanese people of both sexes. (b) The survey analysis on green tea intake indicated that the inhabitants of the areas with low SMR due to stomach cancer seemed to have been much more habitual in drinking green tea compared with those of the areas with high SMR. (c) Oral administration of crude extracts of green tea leaves inhibited the growth of mouse sarcoma 180 inoculated into mice. And intraperitoneal administration of (-)-epigallocatechin gallate (the main component of green tea tannin) also suppressed the growths of Ehrlich tumors implanted into mice and the methylcholanthrene-induced tumors implanted into rats. (d) Oral administration of crude green tea extracts inhibited the incidences of the carcinomas in both esophagus and forestomach in mice, induced by in vivo formation of nitrososarcosine from its precursors, sarcosine and sodium nitrite. These results strongly suggested that Japanese green tea plays a role in protecting against cancer risk.
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20 Ohno Y, Aoki K, Obata K, Morrison AS. Case-control study of urinary bladder cancer in metropolitan Nagoya. Natl Cancer Inst Monogr. 1985 Dec;69:229-34.

We conducted a population-based case-control study of patients with bladder cancer and of controls drawn randomly from the general population of Metropolitan Nagoya and interviewed both groups. The incidence rates of bladder cancer were 2.42 and 7.05/100,000 for females and males, respectively. The analysis, based on 293 patients and 589 controls who were frequency matched for age, sex, and residence, provided the following major findings. Age-adjusted relative risks of 1.89 (1.15-3.10) and 3.53 (1.71-7.27) were found in male and female cigarette smokers, respectively. Significant relative risk was also found in males who drank cocoa. Elevated risk with a dose-response relationship was observed among women who used hair dye and who smoke, but this risk was insignificant, with the disappearance of a dose-response relationship, when it was adjusted for smoking. Age- and smoking-adjusted relative risk of coffee drinking was insignificant with no dose-response relationship. Relative risk of artificial sweetener use was below 1 with adjustment for age and smoking. Intake of alcoholic beverages and cola was insignificantly associated. Reduced risk of significance was suggested for the intake of black tea and matcha (powdered green tea) in females and of fruit juice in males.
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21 Ohno Y, Wakai K, Genka K, Ohmine K, Kawamura T, Tamakoshi A, Aoki R, Senda M, Hayashi Y, Nagao K, et al. Tea consumption and lung cancer risk: a case-control study in Okinawa, Japan. Jpn J Cancer Res. 1995 Nov;86(11):1027-34.

To disclose the relationship between tea consumption and lung cancer risk, we analyzed the data from a case-control study conducted in Okinawa, Japan from 1988 to 1991. The analysis, based on 333 cases and 666 age-, sex- and residence-matched controls, provided the following major findings. (a) The greater the intake of Okinawa tea (a partially fermented tea), the smaller the risk, particularly in women. For females, the odds ratios (and 95% confidence intervals) for those who consumed 1-4, 5-9, and 10 cups or more of Okinawan tea every day, relative to non-daily tea drinkers, were 0.77 (0.28-2.13), 0.77 (0.26-2.25) and 0.38 (0.12-1.18), respectively (trend: P = 0.032). The corresponding odds ratios for males were 0.85 (0.45-1.55), 0.85 (0.45-1.56) and 0.57 (0.31-1.06) (trend: P = 0.053). (b) The risk reduction by Okinawan tea consumption was detected mainly in squamous cell carcinoma. Daily tea consumption significantly decreased the risk of squamous cell carcinoma in males and females, the odds ratios being 0.50 (95% confidence interval 0.27-0.93) and 0.08 (0.01-0.68), respectively. These findings suggest a protective effect of tea consumption against lung cancer in humans.
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22 Setiawan VW, Zhang ZF, Yu GP, Lu QY, Li YL, Lu ML, Wang MR, Guo CH, Yu SZ, Kurtz RC, Hsieh CC. Protective effect of green tea on the risks of chronic gastritis and stomach cancer. Int J Cancer 2001;92:600-4.

Despite the declining trend, stomach cancer remains the second most common cancer worldwide. We examined the role of green tea consumption on chronic gastritis and stomach cancer risks. A population-based case-control study was conducted in Yangzhong, China, with 133 stomach cancer cases, 166 chronic gastritis cases, and 433 healthy controls. Epidemiologic data were collected by standard questionnaire and odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models in SAS. Inverse association was observed between green tea drinking and chronic gastritis and stomach cancer risks. After adjusting for age, gender, education, body mass index, pack-years of smoking and alcohol drinking, ORs of green tea drinking were 0.52 (95% CI: 0.29-0.94) and 0.49 (95% CI: 0.31-0.77) for stomach cancer and chronic gastritis, respectively. In addition, dose-response relationships were observed with years of green tea drinking in both diseases. The results provide further support on the protective effect of green tea against stomach cancer. This is the first time that green tea drinking was found to be protective against chronic gastritis, which may be of importance when designing intervention strategies for stomach cancer and its pre-malignant lesions in the high-risk population.
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23 Shibata K, Moriyama M, Fukushima T, Kaetsu A, Miyazaki M, Une H. Green tea consumption and chronic atrophic gastritis: a cross-sectional study in a green tea production village. J Epidemiol 2000;10:310-6.

Chronic atrophic gastritis (CAG) is well known as a precancerous lesion of the stomach, and Helicobacter pylori (H. pylori) infection increases the risk of CAG. While recent studies have reported that green tea consumption decreases the risk of gastric cancer, there has been no study analyzing the relationship between green tea consumption and the both risks H. pylori infection and CAG. We conducted a cross-sectional study on 636 subjects living in a farming village in Japan to examine the relationship among green tea consumption, H. pylori infection, and CAG. Smoking, alcohol drinking, consumption of four beverages, including green tea, and of five foods were investigated as lifestyle factors that may affect H. pylori infection and CAG. The measurement of H. pylori-IgG antibodies was used to define H. pylori infection, and serum pepsinogens were used to define of CAG. The unconditional logistic regression model was used for analyzing each odds ratio (OR). H. pylori infection was positively associated with the risk of CAG (OR = 3.73; 95% confidence interval [CI], 2.59-5.36). High green tea consumption (more than 10 cups per day) was negatively associated with the risk of CAG, even after adjustment for H. pylori infection and lifestyle factors associated with green tea consumption (OR = 0.63; 95% CI, 0.43-0.93). These results support the hypothesis that high green tea consumption prevents CAG.
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24 Wakai K, Ohno Y, Obata K, Aoki K. Prognostic significance of selected lifestyle factors in urinary bladder cancer. Jpn J Cancer Res 1993 Dec;84(12):1223-9.

To examine the prognostic significance of lifestyle factors in urinary bladder cancer, we conducted a follow-up study of 258 incident bladder cancer patients, who were originally recruited in a case-control study in metropolitan Nagoya. Information on individual survivals was obtained from the computer data-file of the tumor registry of the Nagoya Bladder Cancer Research Group. Univariate analyses revealed significant associations of 5-year survivorship with educational attainment, marital status, drinking habits and consumption of green tea in males, and age at first consultation, histological type and grade of tumor, stage and distant metastasis in both sexes. After adjustment for age, stage, histology (histological type and grade) and distant metastasis by means of a proportional hazards model, drinking of alcoholic beverages was significantly associated with the prognosis of bladder cancer in males. Its adjusted hazard ratio was 0.46 (95% confidence interval: 0.26-0.79), favoring patients who had taken alcoholic beverages. In detailed analysis, ex-drinkers and all levels of current drinkers demonstrated hazard ratios smaller than unity, although no clear dose-response relationship was detected. No prognostic significance was found for such lifestyle factors as smoking habit, uses of artificial sweeteners and hairdye, and consumption of coffee, black tea, matcha (powdered green tea) and cola.
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25 Wang M, Guo C, Li M. A case-control study on the dietary risk factors of upper digestive tract cancer. Zhonghua Liu Xing Bing Xue Za Zhi. 1999 Apr;20(2):95-7.

OBJECTIVE: To understand the effect of dietary factors in Yangzhong, Jiangsu Province-a high prevalence area in China.
METHODS: A case-control study on 209 cases of upper digestive tract cancer was conducted. There were 68 cases of esophageal cancer, 69 cases of cardiac cancer and 72 cases of other gastric cancers including 129 males and 80 females aged 35-79 under the study.
RESULTS: It is revealed that intake of pickled vegetables increases the ORs of esophageal, cardiac and other gastric cancers (OR = 2.82, OR = 5.17, OR = 2.92, respectively). It is also concluded that the intake of leftovers can elevate the ORs of esophageal and cardiac gastric cancer (OR = 1.88 and OR = 1.90) and over consumption of salt also elevates the OR of cardiac cancer (OR = 1.87). However, drinking green tea may decrease the ORs of esophageal and other gastric cancers (OR = 0.20 and OR = 0.28) while fruits consumption may reduce the OR of esophageal cancers (OR = 0.51).
CONCLUSION: Tumors from upper digestive tract have some relations with diet factors but the effects vary with the differences of tumor sites, dose of exposure and area, etc.
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26 Wu AH, Yu MC, Tseng CC, Hankin J, Pike MC. Green tea and risk of breast cancer in Asian Americans. Int J Cancer. 2003;106(4):574-9.

There is substantial in vitro and in vivo evidence implicating tea polyphenols as chemopreventive agents against various cancers. However, epidemiologic data obtained from mainly Western populations are not supportive of a protective role of tea, mainly black tea, in the etiology of breast cancer. Much less is known about the relationship between green tea and breast cancer risk. During 1995-1998, we conducted a population-based, case-control study of breast cancer among Chinese, Japanese and Filipino women in Los Angeles County and successfully interviewed 501 breast cancer patients and 594 control subjects. Detailed information on menstrual and reproductive factors; dietary habits, including intake of black and green tea; and other lifestyle factors was collected. Risk of breast cancer was not related to black tea consumption. In contrast, green tea drinkers showed a significantly reduced risk of breast cancer, and this was maintained after adjusting for age, specific Asian ethnicity, birthplace, age at menarche, parity, menopausal status, use of menopausal hormones, body size and intake of total calories and black tea. Compared to women who did not drink green tea regularly (i.e., less than once a month), there was a significant trend of decreasing risk with increasing amount of green tea intake, adjusted odds ratios being 1.00, 0.71 (95% confidence interval [CI] 0.51-0.99) and 0.53 (95% CI 0.35-0.78), respectively, in association with no, 0-85.7 and >85.7 ml of green tea per day. The significant inverse association between risk of breast cancer and green tea intake remained after further adjustment for other potential confounders, including smoking; alcohol, coffee and black tea intake; family history of breast cancer; physical activity; and intake of soy and dark green vegetables. While both green tea and soy intake had significant, independent protective effects on breast cancer risk, the benefit of green tea was primarily observed among subjects who were low soy consumers. Similarly, the protective effect of soy was primarily observed among subjects who were nondrinkers of green tea. In summary, our results point to an important role of both green tea and soy intake in relation to breast cancer risk in Asian-American women.
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27 Ye WM, Yi YN, Luo RX, Zhou TS, Lin RT, Chen GD. Diet and gastric cancer: a casecontrol study in Fujian Province, China. World J Gastroenterol. 1998 Dec;4(6):516-518.

AIM: To explore the relationship between consumption of fish sauce, other dietary factors, living habits and the rish kf gastric cancer.
METHODS: From May 1994 to July 1995, a population-based 1 2 case-control study was in Carried out inhigh-risk areas of gastric cancer, Changle and Fuqing cities, Fujian Province. Totally 272 cases and 544 age, gender-matched controls were included. Risk state analyses were made by ASRS package.
RESULTS: Risk state single-factor analysis indicated that gastric cancer risk rose with high intake of fish sauce (OR =2.57), salted vegetables (OR =1.41), salted/fried fish and small shrimps (OR =1.57), low consumption of fresh vegetables (OR =1.95), fresh citrus fruits (OR =1.41), other fresh fruits (OR =1.31), green tea (OR =1.72), exposure to moldy foods (OR =2.32), irregular dinners (OR =5.47) and familial history of malignancy (OR =3.27).No significant relationship was observed between smoking, drinking, salt intake, use of refrigerator and gastric cancer risk. The results of risk state conditional Logistic regression showed that fish sauce, salted/dried fish and small shrimps, irregular dinners, familial history of malignancy were included in the best risk set. The summary ARS for the four factors was 75.49%.
CONCLUSION: High intake of fish sauce, salted foods, moldy foods, irregular dinners and familial history of malignancy were possible risk factors for gastric cancer, whereas fresh vegetables and fruits and green tea might have protective effects for gastric cancer.
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28 Yu GP, Hsieh CC, Wang LY, Yu SZ, Li XL, Jin TH. Green-tea consumption and risk of stomach cancer: a population-based case-control study in Shanghai, China. Cancer Causes Control. 1995 Nov;6(6):532-8.

The effect of drinking Chinese green tea on the risk of stomach cancer was evaluated in a population-based case-control study conducted in Shanghai, China, from October 1991 to December 1993. Eligible cases were incident cases of primary stomach cancer diagnosed during the study period among residents of Hongkou district and Nanhui county aged under 80 years. Controls were selected from the same street or commune where the case resided and were matched to the cases on age (within three years) and gender. A total of 711 cases and 711 matched controls, more than 90 percent of the eligible subjects, completed the interview. Information was obtained on the types of tea used, age when habitual tea drinking started, frequency of new batches of tea leaves used per day, number of cups brewed from each batch, total duration of drinking for each batch, strength and temperature of the tea consumed. Statistical analysis was based on modeling through conditional logistic regression. After adjusting for age, gender, place of residence, education, birthplace, alcohol consumption, and cigarette smoking, the odds ratio (OR) comparing drinkers of green tea with nondrinkers was 0.71 (95 percent confidence interval = 0.54-0.93). The adjusted OR decreased with increasing number of new batches of the green tea consumed each day (P value trend = 0.006). With the largest series of stomach cancer cases to date, this study found green-tea consumption associated with lower risk of stomach cancer. Among drinkers of green tea, the risk of stomach cancer did not depend on the age when habitual green-tea drinking started. Green tea may disrupt gastric carcinogenesis at both the intermediate and the late stages.
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29 Yu GP, Hsieh CC. Risk factors for stomach cancer: a population-based case-control study in Shanghai. Cancer Causes Control. 1991 May;2(3):169-74.

A population-based case-control study of stomach cancer was conducted among the teachers and staff of primary and middle schools in Shanghai. A total of 84 cases of stomach cancer were identified in all schools and 2,676 controls were drawn from the teachers and staff of a randomly selected sample of 40 primary and 15 middle schools. Data were analyzed by a multivariate logistic regression model. The analysis indicated that a positive family history of stomach cancer, cigarette smoking, low consumption of fruits, and low consumption of strong tea were significantly associated with stomach cancer incidence.
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30 Zhang M, Binns CW, Lee AH. Tea consumption and ovarian cancer risk: a case-control study in China. Cancer Epidemiol Biomarkers Prev 2002;11:713-8.

To investigate whether tea consumption has an etiological association with ovarian cancer, a case-control study was conducted in China during 1999-2000. The cases were 254 patients with histologically confirmed epithelial ovarian cancer. The 652 controls comprised 340 hospital visitors, 261 non-neoplasm hospital outpatients, and 51 women recruited from the community. Information on the frequency, type, and duration of tea consumption was collected by personal interview using a validated questionnaire. The risk of ovarian cancer for tea consumption was assessed using adjusted odds ratios based on multivariate logistic regression analysis, accounting for confounding demographic, lifestyle, and familial factors including hormonal status and family ovarian cancer. The ovarian cancer risk declined with increasing frequency and duration of overall tea consumption. The adjusted odds ratio was 0.39 for those drinking tea daily and 0.23 for those drinking tea for >30 years, compared with nontea drinkers. The dose response relationships were significant, and the inverse association with ovarian cancer was observed for green tea consumption. The authors concluded that increasing frequency and duration of green tea drinking can reduce the risk of ovarian cancer.
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31 Zhong L, Goldberg MS, Gao YT, Hanley JA, Parent ME, Jin F. A population-based case-control study of lung cancer and green tea consumption among women living in Shanghai, China. Epidemiology. 2001 Nov;12(6):695-700.

Epidemiologic evidence regarding the association between the consumption of green tea and lung cancer is limited and inconclusive, although experimental studies have shown consistently that tea preparations and tea polyphenols may inhibit the induction of a variety of cancers, including lung cancer. In this population-based case-control study, we examined the association between past consumption of green tea and the risk of lung cancer. We identified 649 incident cases of primary lung cancer among women diagnosed from February 1992 through January 1994 using the population-based Shanghai Cancer Registry. We randomly selected a control group of 675 women from the Shanghai Residential Registry, frequency-matched to the expected age distribution of the cases. Green tea consumption was ascertained through face-to-face interviews. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) using unconditional logistic regression. Among nonsmoking women, consumption of green tea was associated with a reduced risk of lung cancer (OR = 0.65; 95% CI = 0.45-0.93), and the risks decreased with increasing consumption. We found little association, however, among women who smoked (OR = 0.94; 95% CI = 0.40-2.22). The inconsistency in the association between drinking tea and the risk of lung cancer reported in previous studies may in part be due to inadequate control of confounding of active smoking.
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32 Jian L, Xie LP, Lee AH, Binns CW. Protective effect of green tea against prostate cancer: a case-control study in southeast China. Int J Cancer. 2004 Jan 1;108(1):130-5.

To investigate whether green tea consumption has an etiological association with prostate cancer, a case-control study was conducted in Hangzhou, southeast China during 2001-2002. The cases were 130 incident patients with histologically confirmed adenocarcinoma of the prostate. The controls were 274 hospital inpatients without prostate cancer or any other malignant diseases, and matched to the age of cases. Information on duration, quantity and frequency of usual tea consumption, as well as the number of new batches brewed per day, were collected by face-to-face interview using a structured questionnaire. The risk of prostate cancer for tea consumption was assessed using multivariate logistic regression adjusting for age, locality, education, income, body mass index, physical activity, alcohol consumption, tobacco smoking, total fat intake, marital status, age at marriage, number of children, history of vasectomy and family history of prostate cancer. Among the cases, 55.4% were tea drinkers compared to 79.9% for the controls. Almost all the tea consumed was green tea. The prostate cancer risk declined with increasing frequency, duration and quantity of green tea consumption. The adjusted odds ratio (OR), relative to non-tea drinkers, were 0.28 (95% CI = 0.17-0.47) for tea drinking, 0.12 (95% CI = 0.06-0.26) for drinking tea over 40 years, 0.09 (95% CI = 0.04-0.21) for those consuming more than 1.5 kg of tea leaves yearly, and 0.27 (95% CI = 0.15-0.48) for those drinking more than 3 cups (1 litre) daily. The dose response relationships were also significant, suggesting that green tea is protective against prostate cancer.
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