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The Journal of Nutrition Nutritional Epidemiology

Drinking Green Tea Modestly Reduces Breast Cancer Risk1,2
Martha J. Shrubsole,3* Wei Lu,4 Zhi Chen,3 Xiao Ou Shu,3 Ying Zheng,5 Qi Dai,3 Qiuyin Cai,3 Kai Gu,5 Zhi Xian Ruan,4 Yu-Tang Gao,4 and Wei Zheng3
3 Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt School of Medicine, Nashville, TN 37232; 4Department of Epidemiology, Shanghai Cancer Institute, Shanghai 200032, People’s Republic of China; and 5Shanghai Center for Disease Prevention and Control, Shanghai 200032, People’s Republic of China

Abstract
Green tea is a commonly consumed beverage in China. Epidemiological and animal data suggest tea and tea polyphenols may be preventive against various cancers, including breast cancer. Catechol-O-methyltransferase (COMT) catalyzes catechol estrogens and tea polyphenols. The COMT rs4680 AA genotype leads to lower COMT activity, which may affect the relationship between green tea consumption and breast cancer risk. We evaluated whether regular green tea consumption was associated with breast cancer risk among 3454 incident cases and 3474 controls aged 20–74 y in a population-based case-control study conducted in Shanghai, China during 1996–2005. All participants were interviewed in person about green tea consumption habits, including age of initiation, duration of use, brew strength, and quantity of tea. Odds ratios (OR) and 95% CI were calculated for green tea consumption measures and adjusted for age and other confounding factors. Compared with nondrinkers, regular drinking of green tea was associated with a slightly decreased risk for breast cancer (OR, 0.88; 95% CI, 0.79–0.98). Among premenopausal women, reduced risk was observed for years of green tea drinking (P–trend ¼ 0.02) and a dose-response relationship with the amount of tea consumed per month was also observed (P-trend ¼ 0.046). COMT rs4680 genotypes did not have a modifying effect on the association of green tea intake with breast cancer risk. Drinking green tea may be weakly associated with a decreased risk of breast cancer. J. Nutr. 139: 310–316, 2009.

Downloaded from jn.nutrition.org by guest on May 7, 2012

Introduction
Tea is a commonly consumed beverage worldwide. Although all tea, black, green, and oolong, originates from the same plant, Camellia sinensis, the properties of these teas differ due to processing (1,2). As a result, green tea, which is processed to prevent fermentation and oxidation, has much higher levels of some antioxidant polyphenols than black tea (1). Epidemiological and animal data suggest that tea and tea polyphenols may be preventive against various cancers (3–5). These polyphenols and other components have been described as having antioxidant (5), pro-oxidant (6), tumor inhibitory (7,8), antiapoptotic (9), antiangiogenesis (10,11), antiestrogenic (12,13), epigenetic (14), and other potentially chemopreventive properties (1,3,4,15,16). In chemical carcinogen-induced cancer studies, green tea has been shown to inhibit or delay tumor formation and burden (7,17).

1

Supported by grant R01CA64277 from the US National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or NIH. 2 Author disclosures: M. J. Shrubsole, W. Lu, Z. Chen, X. O. Shu, Y. Zheng, Q. Dai, Q. Cai, K. Gu, Z. X. Ruan, Y-T Gao, and W. Zheng, no conflicts of interest. * To whom correspondence should be addressed. E-mail: martha.shrubsole@ vanderbilt.edu.

Although tea has been extensively investigated in in vitro and in vivo studies, few epidemiologic studies have evaluated the relationship between green tea and breast cancer risk (18–23) and results from these studies are inconsistent (19–23). In general, the cohort studies, all based in Japan, report no significant association (19,21) and the case-control studies (20,22,23), based on Asian-American or Chinese populations, all report an inverse relationship between green tea and breast cancer risk, although sometimes only among a subgroup (22). Previous studies have not evaluated the relationship between green tea consumption and pre- and postmenopausal breast cancer. Estrogens, estrone, and estradiol are catabolized to catechol estrogens, estrogen metabolites, such as 4-hydroxyestrone and 4-hydroxyestrone, shown to be involved in breast carcinogenesis (24,25). Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of these carcinogenic estrogens to methoxyestradiols and methoxyestrones. COMT also catalyzes the Omethylation of tea polyphenols. In the COMT gene, a G to A transition results in an amino acid change (Val / Met) at codon 108 of soluble COMT and codon 158 of membrane-bound COMT (26). Studies have shown that the AA (Met/Met) genotype of rs4680 in the COMT gene is associated with 50–75% decreased enzyme activity (26–28). Although a recent metaanalysis (29) did not find any evidence that COMT genotypes are

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0022-3166/08 $8.00 ª 2009 American Society for Nutrition. Manuscript received August 21, 2008. Initial review completed September 9, 2008. Revision accepted November 3, 2008. First published online December 11, 2008; doi:10.3945/jn.108.098699.

These included breast cancer in a first degree relative. Controls were randomly selected and were frequency matched on age (5-y intervals) to the expected age distribution of the cases in a 1:1 ratio. how often they changed the tea leaves. Each 25 mL of PCR mixture contained 10 ng DNA.16 mmol/L each of deoxynucleotide triphosphate.2%. Risk factors previously identified as having an independent association with breast cancer in this population were controlled in all models. 0. there was no relationship between age drinking began and breast cancer. regular drinking of green tea was associated with a significant. A detailed description of the methods to determine COMT genotype have been previously published (29). they were also asked about the type of tea they usually consumed (green.98). the type of brew they preferred (light. resident of urban Shanghai. All incident breast cancer cases. and total calorie intake. and number of parity. 0. Comparisons among controls between those who consumed or did not consume green tea regularly are presented (Table 2).or postmenopausal women.independently associated with breast cancer risk. and postmenopausal women. oolong. heavy). Compared with nondrinkers. Detailed information on the validated FFQ has been previously published (33).1 (SAS Institute). although the result was no longer significant among postmenopausal women (OR. The reaction mixture was initially denatured at 95°C for 15 min followed by 35 cycles of 94°C for 45 s. which was defined as at least twice per week for at least 3 mo continuously. restriction enzymes. 0. enrollment period.org by guest on May 7. The DNA fragments were then separated and visualized by electrophoresis on 1. among postmenopausal women and in the total study population. Each PCR product (10 mL) was digested with restriction enzymes (New England BioLabs) at 37°C for 3 h. the age at which they started drinking green tea regularly. The associations between green tea drinking habits and breast cancer risk are presented for the total study population and stratified by menopausal status (Table 3). 2012 Results Comparisons between cases and controls by study phase are presented for select demographic factors. With few exceptions. genomic DNA was extracted from blood samples with the Puregene DNA Purification kit (Gentra Systems) following the protocol of the manufacturer.4 mmol/L of each primer. and 2 unblinded quality control DNA samples. and no previous history of any cancer. Stratified analyses were used to evaluate potential effect modification.05) using SAS version 9.5 mmol/L MgCl2. A total of 1455 (response rate. Age at diagnosis or interview was included as a continuous variable throughout. cases were more likely to have higher educational attainment.1%) and 1999 (83. 0. and 1 unit of HotstarTaq DNA polymerase (Qiagen). an older age at first live birth. were older at first live birth. 13 PCR buffer with 1. other diseases. age at menarche. physical activity. were a younger age at menarche. premenopausal. during August 1996–March 1998 (Phase I) and April 2002–February 2005 (Phase II). the total number of years they had consumed green tea. newly diagnosed during the study period and meeting the following criteria. Tests for multiplicative interaction were done by including multiplicative variables in the logistic model and performing the likelihood ratio test. had higher household income. The study was designed to evaluate the green tea and breast cancer hypothesis.88. Thus. risk factors were comparable between the 2 study phases. regular tea consumers were younger. had a higher educational attainment. PCR primers. and the amount of tea leaves they usually consumed per month or per year. 12% lower risk for breast cancer (OR. Genotyping assays for the COMT rs4680 polymorphism was conducted for cases and controls recruited in Phase I in which blood samples were collected from 1193 (82%) cases and 1310 (84%) controls. were eligible for this study: aged 25–70 y. resulting in a total of 3454 cases and 3474 controls. The study protocols were approved by the Institutional Review Boards of all institutes involved in the study. Compared with those who never drank green tea regularly. history of fibroadenoma. Quality control samples were included in genotyping assays. and dietary factors (Table 1). Controls were selected using the Shanghai Resident Registry. Materials and Methods Participant recruitment. Information on demographic characteristics. Odds ratios (OR) were used to measure the association of breast cancer risk with green tea consumption habits. Excluding a few Phase I participants for whom sufficient DNA was not available or for whom the genotyping assay failed. personal and family history of cancer. All participants were asked whether they drank tea regularly.7%) cases and 1556 (90. Tests for trend were performed by entering the midpoint of each category as a continuous variable in the model. total fruit and vegetable intake. cases were identified primarily through the Shanghai Cancer Registry and diagnoses were confirmed by pathology reviews supplemented by medical record reviews. The PCR was completed by a final extension cycle at 72°C for 8 min. behavioral and dietary habits. and 72°C for 45 s. a positive family history of breast cancer in a first degree relative. We further evaluated whether the relationship between green tea consumption and breast cancer risk was modified by the COMT rs4680 genotype. Detailed study methods have been published elsewhere (31. 59–62°C for 45 s. genotyping data were obtained from 1116 cases and 1191 controls in the green tea analysis.74–1. a personal history of breast fibroadenoma. 91. a population-based registry containing address and demographic information for all residents of urban Shanghai.nutrition. Among those that consumed tea regularly. In both phases and compared with controls. and fat.32). The consistency rate between the quality control and study samples was 96. All statistical tests were based on 2-sided probabilities (a ¼ 0. one previous study has reported green and black tea consumption is protective for breast cancer only among the AA COMT genotype of rs4680 (30). case-control study conducted in Shanghai. 0. In brief. Laboratory methods. In general. respectively. The FFQ was designed to capture usual intake of 76 food items in the 5 y prior to diagnosis and over 85% of foods commonly consumed in Shanghai. a higher waist:hip ratio. after adjusting for potential confounding variables. In this study. China. the questionnaires from both phases were identical. an Tea and breast cancer 311 . The COMT rs4680 genotyping was performed using PCR-restriction fragment length polymorphism. 2 DNA. Asian. Controls had inclusion criteria identical to those of the cases with the exception of a breast cancer diagnosis. and green tea consumption were collected by in-person interviews conducted by trained staff in the participant’s home.3%) and 1918 (70. were more likely to be premenopausal. The laboratory staff was unaware of the identity of the participants. However. established breast cancer risk factors. The Shanghai Breast Cancer Study is a large population-based. moderate. Data collection. The PCR was conducted in a Biometra T Gradient Thermocycler. and were less likely to be physically active in the past 10 y. Briefly. or other).04). age at menopause. Unconditional logistic regression models were used to obtain maximum likelihood estimates of the OR and their 95% CI. black. fruits and vegetables. 0. Data analysis. Models also controlled for age. over 92% drank only green tea. If yes. The pattern was similar for both pre.79–0. China.5– 3% agarose gel containing ethidium bromide. including among Caucasian.88. 95% CI.4%) controls were recruited in Phase I and II. we evaluated green tea consumption habits and risk of breast cancer in a large population-based study of breast cancer in Shanghai. it is not possible to evaluate other types of tea consumption in this study and the analysis was limited to those who did not drink tea regularly and those who consumed green tea regularly. Each 96-well plate contained 1 water. Among premenopausal women. waist:hip ratio. and had higher daily intakes of energy. education. age at first live birth. and length of the resulting fragments are published elsewhere (29). Downloaded from jn. 2 blinded quality control DNA. 95% CI.

Years of drinking was associated with decreased risk among premenopausal women (P-trend ¼ 0. only women with either the lowest or 2nd greatest intake of tea leaves were at a reduced risk of breast cancer (P .3 48.68 Values are means 6 SD or %.1 6 14.0 6 0. green tea intake.0 38.8 5. did not find a significant relationship between breast cancer and green tea (19.01). y Ever had a live birth.6 y was associated with a significantly reduced risk among postmenopausal women (OR.4 6 3. Among postmenopausal women.01 0.03).85 0.81 6 0.8 31.27 0. inability to comprehensively control for confounders. and breast cancer risk stratified by menopausal status (data not shown). % Less than high school High school More than high school Household Income. The relationship between green tea intake and breast cancer risk did not vary according to COMT rs4680 genotype. respectively).7 6 8.04 40.6 35.4 31.0.98 for age of initiation of $41 y vs.0001 .8 39.7 14. % Less than high school High school More than high school Household income.2 0.0.0. Three separate measures of usual dose of tea consumption were evaluated. 0. including a meta-analysis (34). 95% CI.7 47.65– 0. Although the relationship between green tea drinking and breast cancer risk was somewhat weakened in this smaller subset of participants.0. 95% CI.82 6 0.05).0 26. Compared with nondrinkers. Among postmenopausal women.06 30.6 0.7 7342 6 1837 526 6 279 34.0003 . Few studies have reported on the use of green tea and risk for breast cancer.0 6 0.06 24. y Energy intake.9 0. However.5 37.4 7371 6 1804 526 6 274 35.2 25.6 95. 0. Three cohort studies.1 57. % Age at first live birth.6 47.7 95.9 . g/d Fat intake. for premenopausal women (P-trend ¼ 0.2 38.9 45. COMT genotype did not appear to modify the associations.3 40.0 0.6 25. g/d 1 2 Ever 1075 49. 2012 Values are means 6 SD unless otherwise specified.07 . nondrinkers.97 0.2 15. % Low Middle High Family history of breast cancer.06 30.1 6 4.7 6 3. The amount of dry tea leaves consumed per month showed a trend toward a decreased risk of breast cancer among premenopausal women (P-trend ¼ 0.8 96.0001 .06 29. For x-square test (categorical variables) or t test (continuous variables).0.3 6.02). y Postmenopausal.5 46.001 0.6 38.8 7435 6 1894 555 6 290 35.9 48.0 6 8.0001 Downloaded from jn.1 14.0001 0. found no relationship between tea and breast cancer. The associations of green tea drinking and breast cancer risk are presented stratified by COMT rs4680 genotype (Table 4).43–0.046) although not in the highest level of intake. 312 Shrubsole et al.15 0.4 26.1 35. % Age at menopause.2 14.8 0.7 7300 6 1810 513 6 272 33. % Age at menarche.51 0. % History of fibroadenoma.1 21.7 2.80. and a small unexposed .3 0.0001 . % Age at menopause.2 6 8. these studies may have been limited by a small number of cases.7 9. kJ/d Fruit and vegetable intake.2 38.81 6 0. y Education.org by guest on May 7.3 6 9. 0.0001 Never n Age. % Age at first live birth.4 148 6 124 35.0 6 15.87).53 0. g/d Fat intake.8 14. 0. For x -square test (categorical variables) or t test (continuous variables).75 0.53 0.5 11.5 49.7 1. this relationship appeared to be related to years of drinking and measures of frequency and amount.0 5. y Energy intake.0.5 6 1.9 6 4. Among both preand postmenopausal women. g/d Tea consumption Ever.7 48. Phases I and II1 Green tea drinking n Age. OR. We also evaluated COMT genotype.5 31.9 43. g/mo Strength of brew.0. 0.0.81 6 0. kJ/d Fruit and vegetable intake.2 8. all conducted in Japan where green tea consumption is highly prevalent.3 P-value2 TABLE 2 Characteristics of controls by green tea drinking use in the Shanghai Breast Cancer Study.22 0.17 .21).1 49.4 6 4.8 1.7 6 1.61.9 6 10.0002 0.9 53. Risk was also inversely related to frequency of leaf changes in premenopausal women (P-trend ¼ 0. Black tea has been evaluated in several previous studies (34– 39) and most.0.0 6 14.95 0.0.7 14. Discussion In this study.9 6 4.5 6 3.4 6 1.8 96.7 6 1.01 .7 42. % Age at menarche.9 6 3.0 4.12 0.TABLE 1 Characteristics of breast cancer cases and controls in the Shanghai Breast Cancer Study. % History of fibroadenoma. 0. y Postmenopausal.9 6 14.4 3.004 0.3 14.02) and.0.1 30. % Age at first use. % Light Moderate Heavy Change of tea leaves per day 1 2 3371 49.1 34.99.2 15.75.0001 . a preference for heavy brew was associated with a borderline reduced risk for breast cancer in the total study population (P-trend ¼ 0. 0.0 37.or postmenopausal women. We evaluated soy and folate intakes as effect modifiers of the green tea and breast cancer association and did not find any evidence that either of these factors was an effect modifier in this population (data not shown).007 0. 95% CI. particularly. y Tea leaves used. 0. % Low Middle High Family history of breast cancer.0001 .9 24.4 0.57–0. COMT genotype did not modify the association between green tea drinking and breast cancer risk either among pre.4 19. Among premenopausal women. y Education. we found that risk for breast cancer was weakly inversely associated with regular green tea drinking. older age of initiation was associated with decreased risk of breast cancer (OR.nutrition. the relationship was stronger with recent use and lower amounts of intake.001 35.9 6 10. y Ever had a live birth. % Waist:hip ratio Physically active past 10 y.05 .8 P-value2 2305 50.0001 0.0001 .8 2.0001 0. whereas only green tea drinking for . % Waist:hip ratio Physically active past 10 y.7 26.0.4 148 6 130 35. there was a possible U-shaped relationship between amount of tea leaves consumed per month and risk of breast cancer. Phases I and II1 Cases Controls 3380 50.

61 (0.98) 0.00 0.11 2345/2305 364/377 510/528 152/169 1.46) 0. were 0.69–1.00 (ref) 0.58–1.43–0.00) (0.82 0. Only our study and the previous study in a Chinese population (23) had multiple measurements of tea intake and only our study included strength of brew.77–1. including the measurement.86 0.55–0.77 (0.66–1.70–1.6 6–. and fat intake.36) 0.00 0.42) 0.18) 0.00 (ref) 0.12) 0. and a hospital-based study in Southeast China (23).08) (0.72–1.72 (0.59–0.79–0. age at menopause (all participants and postmenopausal analyses only).90 (0.87–1.00 0.88 (0.99) 1.74–1. These other studies reported only 1 measure of tea intake: cups. The Japanese studies. although the Singapore study only observed an association among a subset of women defined by genotype (22).23 $23 P-trend Tea leaves used.84 1.00 0.99 (0.78 0.71–1.21) (0.02 1. a population-based study of Chinese living in Singapore (22).12) (0.27 1.73–1. had virtually no abstainers from tea consumption and very high consumption patterns based on the number of cups per day (18.45) 0.01) (0.19) 1.75 (ref) (0.2 g/mo Never regular #50 50–#100 .08) (0.69–1.56–1. the summary OR.03 956/1054 122/152 204/205 55/61 2345/2305 131/131 854/892 41/52 1389/1251 88/84 532/543 25/30 956/1054 43/47 322/349 16/22 Adjusted for age.36) 0. which are consistent with our finding of a weak association (34.87) 1.00 (ref) 0.TABLE 3 Associations between green tea drinking habits and breast cancer risk in the Shanghai Breast Cancer Study. family history of breast cancer. the hospital-based Chinese study found all measures of green tea drinking were associated with reduced breast cancer risk and many were associated in a dosedependent manner (23).80 (ref) (0.16) 0.11 1.046 956/1054 381/418 956/1054 68/75 89/96 116/103 108/144 1.70–1.88 0.02 (ref) (0. reference group. study phase.80–1.01 1389/1251 242/225 306/324 97/108 1. parity.99) 0.14) 0.07) (0.00 0. in 2 meta-analyses of these studies.00 0.225 P-trend Strength of brew Never regular Light Moderate Heavy P-trend Change of leaves per day Never regular .08 (ref) (0.00) 1.02 (0.31 31–. personal history of fibroadenoma.04) 1.100–#225 .62–1.00 (ref) 0.1 P-trend 1 2345/2305 1026/1075 2345/2305 246/270 272/281 315/294 193/230 1.34–1.88 0.72–1. These findings are in contrast to our observation of a weak association between green tea consumption and breast cancer risk in a large population-based study.83 0. and prevalence of tea consumption.83 (0.74–1.02) 0. education. nearly one-third of the population consumed tea at least twice a week.48–1.87 (0. although not significant.80–1.13) 0.96 0.03) (0.73–1.79–0. milliliters.97 1389/1251 160/144 148/154 129/153 182/178 1.04) 0.74–1.65–0. total fruit and vegetable intake.00) 1.74 (ref) (0.61–1.89 0.88) (0.83 0. age at menarche.58–1.00 (ref) 0.81 (0.85 0.71–1. evaluated green tea drinking and breast cancer risk.77–1.89 0.78 956/1054 57/93 90/82 90/86 144/157 Downloaded from jn.93 0.75 (0. All 3 studies found inverse associations with at least 1 measure of tea drinking.06 (0.24 24–.00 0.00 0.00 1. 2 Test for trend excludes unknown.04) (0.80 (0.35) (0.13) 0.14 14–. a population-based study of Asian Americans in Los Angeles (20).06) 0.03) 0.09 (ref) (0.nutrition.05 (0.78–1.04 (ref) (0.01 1. physical activity.78–1.94 (0.22) (0.30) 0.53–0.81 (ref) (0. Phases I and II All participants Cases/controls OR (95% CI) 1 Premenopausal Cases/controls OR (95% CI) 1 Postmenopausal Cases/controls OR (95% CI)1 Tea consumption Never Ever Age at first use.91 0.1 1 .75–1.21).80–1.04) 0.90 0.76–1.73–1.00 (ref) 0. In contrast to our study.09 1389/1251 645/657 1389/1251 178/195 183/185 199/189 85/86 1.03 0.65–1.03) 0.32) (0.98) (0. with most controls consuming less than daily or weekly (20. There are several notable differences between our and previous studies.00) (0.00 (ref) 0. Most recently.12) (0.93 0.66–0.78–1.90 956/1054 78/107 119/110 80/101 94/90 1.26) 0.00 (ref) 0.88 (0.77–1. 2012 2345/2305 238/251 267/264 209/254 276/268 1.66 (ref) (0.93 0.85 0.72 0.40).99) (0. consumers in 2 of the previous case-control studies reported much higher prevalence of any green tea consumption but much lower average intake of tea. Three case-control studies.89.31) 0. as mentioned previously.88 (0.88 (0.63–1.86 1389/1251 161/167 177/189 196/187 111/114 1.14) (0.81 0.97 (0.27) 0.07) (0.66–1. total energy intake. Over one-half of the hospital-based controls in the previous Chinese study reported drinking green tea and most also Tea and breast cancer 313 .68–1.44–1. age at first live birth.77–1.57–0.98) 1.20) 0.49 2345/2305 218/260 267/271 286/273 255/271 1. definition.89 (0.53–1.00 0.59–1.85 and 0.94 0.76–1. Nonetheless.77–1. waist:hip ratio.61 1.59–1.11) (0.21) (0.01) 0.71 0.06 (0.41 $41 P-trend Years of drinking Never regular .00 (ref) 0.70–1.87 (0.org by guest on May 7.22).13) (0. or frequency.00) 0. y Never regular . In our study.70–1.28) (0.92) (0.66–1.86 (0.72 (0.

75 420 25 89 62 416 24 92 83 347 27 66 57 382 24 80 68 0.38 (0.41 1.48).76 420 91 85 416 102 97 347 74 76 382 92 80 0. Furthermore.68–1. total fruit and vegetable intake.68–1.44).43 1.19) 0.68–1.63–1.00 (Ref) 0.71–1.85 (0.67–1. On the one hand.04 (0. consumption of green tea was associated with reduced levels of estrogens. In addition. which have antiestrogenic effects. Green tea components. It is also possible that we did not observe consistent relationships among postmenopausal women because the sample size was smaller than for premenopausal women. the key enzyme converting androgens to estrone or estradiol (12).43–2.33) 0.95 0. but. downregulate telomerase (42).15) 0.62–1.51 (Ref) (0.10) 0.99) (0.89 (0.33 (Ref) (0.47.86 0.00 (Ref) 0.org by guest on May 7. The authors found the inverse relationship they initially observed between tea intake and breast cancer (20) was primarily limited to those individuals with at least 1 low activity allele (30).11) 0. age at first live birth.10 1.16) 0.51–1. 2 Test for trend excludes unknown. waist:hip ratio. on the other hand.00 (Ref) 0.68 (0. 2012 0.00 1.32) 0.41). age at menarche.2 P-interaction Regular green tea consumption Never Ever Age at first use.31 0.1 or 1 .1 P-trend 1 420 176 420 82 94 416 199 416 100 99 1.95 (0. total energy intake.10) (0.84 (0. upregulate or maintain intercellular gap junction communication (45.86 (0. y Never regular .58–1. however.2 Val/Met or Met/Met (AG. and estradiol among pre.55–1.14 347 139 11 382 161 11 1.43.00 (Ref) 0. age at menopause (all participants and postmenopausal analyses only).78 (0.00 (Ref) 0. estrogen plays a critical role in breast carcinogenesis.nutrition. parity.60–1.00 (Ref) 0. affect cell cycle arrest (41).98) 1. including green tea.06) 0.76 Adjusted for age. and increase apoptosis (41). and breast cancer risk (30).75 0.62–1.57–1.15 1.56–1.TABLE 4 Associations between green tea drinking habits and breast cancer risk stratified by COMT genotype in the Shanghai Breast Cancer Study.00 (Ref) 0. even though the prevalence was much higher than in our study. green tea has also been described as having antiestrogenic properties.73 420 79 85 416 97 91 347 70 71 382 73 92 Downloaded from jn.91 (0. personal history of fibroadenoma.73 (0. and fat intake.50–1. a prevalence that is much higher but a frequency that is similar to our study.87 (0. There are also plausible mechanisms by which COMT and green tea may interact to affect breast cancer risk. No previous study has evaluated the association between green tea and breast cancer by menopausal status.55–1.47–0.00 (Ref) 0. consumed the tea at least daily. found no evidence that the COMT rs4680 genotype affected the relationship between green tea consumption and breast cancer .10) 1.00 (Ref) 0.52 1. have antioxidant properties (5). AA) Cases Controls OR (95% CI)1.88 0.12) 1. Several plausible mechanisms have been proposed for green tea’s possible chemopreventive properties. suppress cellular proliferation (18.08 0.20) 0.66–1. among other activities.59–1.46).10) 347 150 347 71 79 382 172 382 96 76 1. In vitro studies found that tea polyphenols inhibit aromatase.100 P-trend Strength of brew Never regular Light Moderate Heavy P-trend Change of leaves per day Never regular .52–1. education.82 (0.51–1.00 0.68) (0.78 (0. However.18) 0.49) 0.13–1. Phase I COMT genotype (rs4680) Val/Val (GG) Cases Controls OR (95% CI)1.47) 0. Our 314 Shrubsole et al.94 (0.02 (0.00 (Ref) 0. study suggests the association between green tea drinking and breast cancer risk may differ by menopausal status and the inverse association with measures of longer duration and larger dose may be more pronounced among premenopausal women.11) 1.and postmenopausal women (13.32) 0.31 1. We. low activity may also lead to a slower metabolism of tea polyphenols.84 (0.92 0.2 g/mo Never regular #100 .60–1. inhibit vascular endothelial growth factor (18. COMT rs4680 genotype.76 0.31 31–411 P-trend Years of drinking Never regular .14 14–231 P-trend Tea leaves used.27) 0. low COMT activity may lead to elevated levels of catechol estrogens.81 (0. the amount of dried tea leaves consumed per year was substantially less than the amount of tea leaves reported by our population-based controls in another part of China. whereas only recent and mild use is associated with decreased risk among postmenopausal women. A population-based study of Asian Americans is the only previous study to evaluate tea consumption. estrone. physical activity. family history of breast cancer.96 420 171 5 416 187 12 1. As a hormone-dependent cancer.28) 0.34) (0.

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