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Nutrition and Cancer Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/hnuc20
Endometrial Cancer in Relation to Coffee, Tea, and Caffeine Consumption: A Prospective Cohort Study Among Middle-Aged Women in Sweden Elisabete Weiderpass f
abcd
a
a
ae
f
, Sven Sandin , Marie Lof , Jin-Kyoung Oh , Manami Inoue , Taichi f
ag
Shimazu , Shoichiro Tsugane & Hans-Olov Adami a
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden b
The Cancer Registry of Norway, Oslo, Norway
c
Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland
d
Click for updates
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway e
Risk Appraisal and Prevention Branch, National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea f
Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan g
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Published online: 02 Sep 2014.
To cite this article: Elisabete Weiderpass, Sven Sandin, Marie Lof, Jin-Kyoung Oh, Manami Inoue, Taichi Shimazu, Shoichiro Tsugane & Hans-Olov Adami (2014) Endometrial Cancer in Relation to Coffee, Tea, and Caffeine Consumption: A Prospective Cohort Study Among Middle-Aged Women in Sweden, Nutrition and Cancer, 66:7, 1132-1143, DOI: 10.1080/01635581.2014.948214 To link to this article: http://dx.doi.org/10.1080/01635581.2014.948214
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Nutrition and Cancer, 66(7), 1132–1143 Copyright Ó 2014, Taylor & Francis Group, LLC ISSN: 0163-5581 print / 1532-7914 online DOI: 10.1080/01635581.2014.948214
Endometrial Cancer in Relation to Coffee, Tea, and Caffeine Consumption: A Prospective Cohort Study Among Middle-Aged Women in Sweden Elisabete Weiderpass
Downloaded by [Michigan State University] at 03:37 27 February 2015
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; The Cancer Registry of Norway, Oslo, Norway; Department of Genetic Epidemiology, Folkh€ alsan Research Center, Helsinki, Finland; and Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
Sven Sandin and Marie Lof Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Jin-Kyoung Oh Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden and Risk Appraisal and Prevention Branch, National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea
Manami Inoue, Taichi Shimazu, and Shoichiro Tsugane Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan
Hans-Olov Adami Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden and Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
This study aimed to add to prospective data on the possible inverse association between coffee consumption and endometrial cancer risk, already supported by several case-control studies. Coffee and tea consumption and possible confounding factors were assessed among 42,270 women aged 30–49 years at enrollment in 1991–1992 in the Swedish Women’s Lifestyle and Health cohort study, with complete follow-up through 2009. We calculated caffeine intake per day; Cox proportional hazard models were used to estimate multivariable relative risks (mRR) for endometrial cancer with 95% confidence intervals (CIs). One hundred forty-four endometrial cancers were diagnosed during follow-up. Women with and without endometrial cancer had a similar mean daily coffee consumption (549 vs. 547 g), tea consumption (104 vs. 115 g), and caffeine intake (405 vs.
Submitted 2 October 2013; accepted in final form 12 June 2014. Address correspondence to Elisabete Weiderpass, Department of Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, 171 77 Stockholm, Sweden. Tel.: C358-408453406. Fax: C 358919125727. E-mail: [email protected]
1132
406 mg). Compared to those consuming 3 cups had a mRR of 1.56 (95% CI: 0.94–2.59; P for trend D 0.17). Compared with the lowest tertile of caffeine intake, the highest tertile had a mRR of 1.32 (95% CI: 0.87–1.99; P for trend D 0.27). Our study provides no convincing evidence of an association between coffee consumption, tea consumption, or caffeine intake and endometrial cancer risk among middle-aged women.
INTRODUCTION Several case-control studies, cohort studies, and three metaanalyses have suggested an inverse association between coffee consumption and endometrial cancer risk. The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) reported that coffee probably protects against endometrial cancer (1). If such a causal association exists, it would have considerable implications. Indeed, after water, coffee and tea are the most commonly consumed beverages in the world. Coffee consumption is especially high in Northern
Downloaded by [Michigan State University] at 03:37 27 February 2015
CAFFEINE AND ENDOMETRIAL CANCER IN WOMEN IN SWEDEN
Europe and North America. Moreover, a great variety of herbal infusions, such as mate, a traditional hot drink in parts of South America, also contain caffeine, a chemical substance present in coffee and tea. Endometrial cancer risk has been previously associated with several host factors, including high body mass index (BMI), nulliparity or low parity, early age at first birth, not using hormonal contraceptives, and use of hormone replacement therapy (in particular estrogens without progestins or with progestins added to estrogens for less than the full treatment cycle). History of type 2 diabetes mellitus (noninsulin dependent), family history of cancer, particularly endometrial cancer, and use of drugs to prevent breast cancer recurrence or de novo breast cancer, such as Tamoxifen, are also associated factors. In addition, endogenous hormone levels have been positively associated with endometrial cancer risk in several prospective cohort studies (2), whereas cigarette smoking decreases risk. Although high BMI has been associated with endometrial cancer risk, no dietary factor has been singled out as being etiologically associated with any certainty (3). Consumption of alcoholic beverages is not associated with endometrial cancer risk (4). An association between coffee or tea consumption and endometrial cancer is biologically plausible, as several active compounds in coffee and tea could have an effect on endogenous hormone levels. Caffeine is one of these compounds, but its effect on endogenous hormones may be modified by BMI (5). Overweight and obese women have a high production of endogenous hormones due to aromatization of androstenedione to estrone in fat tissue. This mechanism is the main explanation for the increased risk of postmenopausal endometrial cancer observed in overweight and obese women (6). Several epidemiological studies have demonstrated an association between type 2 diabetes mellitus and endometrial cancer risk (7–9). Insulin resistance and hyperinsulinemia, conditions that precede type 2 diabetes mellitus, may play a role in the etiology of endometrial cancer (6). Insulin has been shown to stimulate the growth of endometrial stromal cells by binding to insulin receptors on endometrial cells. Insulin may also increase levels of bioactive estrogens by decreasing concentrations of circulating sex hormone binding globulin (6). Coffee consumption may reduce the risk of type 2 diabetes mellitus (10) and lower plasma concentrations of C-peptide, a marker of insulin secretion, among women without type 2 diabetes mellitus (11). Coffee or its compounds may modulate two hormonal factors known to be related to endometrial cancer risk: insulin and estrogen (6), and thus reduce endometrial cancer risk (8,9). The chemical compounds in coffee that may affect carcinogenesis are chlorogenic acids, caffeine, and the coffee diterpenes cafestol and kahweol. We present here prospective data on coffee consumption, black tea consumption, and total caffeine intake, and the incidence of endometrial cancer in women participating in the Swedish Women’s Lifestyle and Health (WLH) cohort study.
1133
Our hypothesis is that coffee and tea consumption and caffeine intake are inversely associated with endometrial cancer incidence in a dose-dependent manner, and that this inverse association is more evident in overweight and obese women (BMI 25), as indicated by Friberg et al. (5), as well as in nonsmokers and never smokers. We also present risk estimates for other potential risk factors.
SUBJECTS AND METHODS Study Population The study cohort and exposure assessment have previously been described in detail (12,13). The source population of this study was comprised of women aged 30–49 years, residing in the Uppsala Health Care Region in Sweden between 1991 and 1992. From this source population, 96,000 women were randomly selected from four age strata (30–34, 35–39, 40–44, and 45–49 years) and were invited to participate in the Swedish component of the Scandinavian WLH cohort study. The women were asked to fill in a questionnaire, which included a food frequency questionnaire (FFQ) component. Of those invited, 49,261 returned the questionnaire and were enrolled in the study. A follow-up questionnaire was completed in 2002–2003 by a subgroup of the enrolled cohort (34,415 women). The Swedish Data Inspection Board and the regional Ethical Committee approved the study. Consent was assumed by the return of the postal questionnaire. We excluded 2694 women, or 10% of the original cohort, from the present analysis as follows: 1483 women who underwent hysterectomy before cohort enrollment, 950 with energy intake outside the 1st (1847 kJ/day) and 99th (12,474 kJ/day) percentiles, nine women with endometrial cancer before enrollment, 244 with breast cancer before cohort enrollment, seven women who had emigrated; and one woman whose questionnaire was considered unreliable due to several contradictory answers. Furthermore, we excluded 4297 women with missing values for the variables used in various analyses (485 of these were missing information on hysterectomy). The remaining 42,270 women were included in most analyses.
Exposure Assessment Coffee consumption was assessed in an open-ended question that asked how many cups per day or per week women consumed during the preceding year. One cup of coffee was estimated to contain 150 g. Tea intake during the preceding year was assessed within the FFQ using 9 prespecified frequencies ranging from never or seldom to three times per day. They also reported the portion size as small, medium or large (0.5, 1, or 1.5 cups). One cup of tea was estimated to contain 200 g. When similar questions were used in a comparable population of women, Spearman correlations between coffee and tea consumption and weighted records for coffee and tea
1134
E. WEIDERPASS ET AL.
Downloaded by [Michigan State University] at 03:37 27 February 2015
were 0.6 and 0.7, respectively (14). Caffeine intake (in g/day) was calculated based on the sum of the estimated amounts of caffeine in coffee and tea (15). In the present analyses, values were set as follows: 69 mg of caffeine per 100 g of coffee; and 25 mg caffeine per 100 g of tea (15). We had no specific information on use of sugar, sweetener, creamers, or milk in coffee or tea in our questionnaire.
Follow-Up The cohort was followed from the date of return of the questionnaires until December 31, 2009 through linkages with the Swedish Cancer Registry, Mortality Registry, and Population Registry (which records migrations). Follow-up time was calculated as the date of entry into the cohort until the occurrence of incident invasive endometrial cancer, emigration, death, incident invasive breast cancer, or the end of the observation period, whichever came first. We censored individuals with a diagnosis of invasive breast cancer during follow-up before endometrial cancer diagnosis, because Tamoxifen use, a risk factor for endometrial cancer, was widespread in Sweden during the follow-up period. We censored women who underwent hysterectomy during follow-up (n D 3457, 8.2% of 42,270 women), identified through linkage with the patient registry (surgery). Hysterectomy 21 days before endometrial cancer diagnosis was not censored as it was assumed the hysterectomy was performed as a result of endometrial cancer. Our outcome was defined as a diagnosis of invasive endometrial cancer (ICD7 D 172.* and 5-digit histological code). Benign tumors (morphology code for ICD-O/2 from 1993 and ICD-O/3 from 2005: 81401 D atypical adenoma, 81402 D a denocarcinoma in situ), tumors classified as unknown if benign, malign, or borderline (morphology code 80701), and nonepithelial endometrial cancers (morphology code 89303 D sarcoma, 89503 D nonepithelial-Mullerian mixed tumor) were not considered. Endometrial tumors were classified as Type 1 (morphology code 81403 D adenocarcinoma and adenocarcinoma not otherwise specified; 814031 D adenocarcinoma, malignant, well differentiated; 814032 D adenocarcinoma, malignant, moderately differentiated; 838031 D endometrioid adenocarcinoma well differentiated; and malign. with missing code) and Type 2 (84603 D papillary serous cystadenocarcinoma; 814033 D adenocarcinoma, malignant, poorly differentiated; 80203 D carcinoma, malign, undifferentiated; 84603 D papillary serous cystadenocarcinoma). Type 2 endometrial cancers were censored in the analysis as the characteristics are different between histological subtypes (Type 1 and 2) and Type 2 is very rare (only 5 incident cases in the study population).
Covariables We adjusted for the potential confounding effect of the following covariables assessed in the baseline questionnaire: BMI (weight in kg divided by height in m2 at cohort enrollment as a
continuous variable and categorized as
Nutrition and Cancer Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/hnuc20
Endometrial Cancer in Relation to Coffee, Tea, and Caffeine Consumption: A Prospective Cohort Study Among Middle-Aged Women in Sweden Elisabete Weiderpass f
abcd
a
a
ae
f
, Sven Sandin , Marie Lof , Jin-Kyoung Oh , Manami Inoue , Taichi f
ag
Shimazu , Shoichiro Tsugane & Hans-Olov Adami a
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden b
The Cancer Registry of Norway, Oslo, Norway
c
Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland
d
Click for updates
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway e
Risk Appraisal and Prevention Branch, National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea f
Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan g
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Published online: 02 Sep 2014.
To cite this article: Elisabete Weiderpass, Sven Sandin, Marie Lof, Jin-Kyoung Oh, Manami Inoue, Taichi Shimazu, Shoichiro Tsugane & Hans-Olov Adami (2014) Endometrial Cancer in Relation to Coffee, Tea, and Caffeine Consumption: A Prospective Cohort Study Among Middle-Aged Women in Sweden, Nutrition and Cancer, 66:7, 1132-1143, DOI: 10.1080/01635581.2014.948214 To link to this article: http://dx.doi.org/10.1080/01635581.2014.948214
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Nutrition and Cancer, 66(7), 1132–1143 Copyright Ó 2014, Taylor & Francis Group, LLC ISSN: 0163-5581 print / 1532-7914 online DOI: 10.1080/01635581.2014.948214
Endometrial Cancer in Relation to Coffee, Tea, and Caffeine Consumption: A Prospective Cohort Study Among Middle-Aged Women in Sweden Elisabete Weiderpass
Downloaded by [Michigan State University] at 03:37 27 February 2015
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; The Cancer Registry of Norway, Oslo, Norway; Department of Genetic Epidemiology, Folkh€ alsan Research Center, Helsinki, Finland; and Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
Sven Sandin and Marie Lof Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Jin-Kyoung Oh Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden and Risk Appraisal and Prevention Branch, National Cancer Control Institute, National Cancer Center, Goyang, Republic of Korea
Manami Inoue, Taichi Shimazu, and Shoichiro Tsugane Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan
Hans-Olov Adami Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden and Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
This study aimed to add to prospective data on the possible inverse association between coffee consumption and endometrial cancer risk, already supported by several case-control studies. Coffee and tea consumption and possible confounding factors were assessed among 42,270 women aged 30–49 years at enrollment in 1991–1992 in the Swedish Women’s Lifestyle and Health cohort study, with complete follow-up through 2009. We calculated caffeine intake per day; Cox proportional hazard models were used to estimate multivariable relative risks (mRR) for endometrial cancer with 95% confidence intervals (CIs). One hundred forty-four endometrial cancers were diagnosed during follow-up. Women with and without endometrial cancer had a similar mean daily coffee consumption (549 vs. 547 g), tea consumption (104 vs. 115 g), and caffeine intake (405 vs.
Submitted 2 October 2013; accepted in final form 12 June 2014. Address correspondence to Elisabete Weiderpass, Department of Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, 171 77 Stockholm, Sweden. Tel.: C358-408453406. Fax: C 358919125727. E-mail: [email protected]
1132
406 mg). Compared to those consuming 3 cups had a mRR of 1.56 (95% CI: 0.94–2.59; P for trend D 0.17). Compared with the lowest tertile of caffeine intake, the highest tertile had a mRR of 1.32 (95% CI: 0.87–1.99; P for trend D 0.27). Our study provides no convincing evidence of an association between coffee consumption, tea consumption, or caffeine intake and endometrial cancer risk among middle-aged women.
INTRODUCTION Several case-control studies, cohort studies, and three metaanalyses have suggested an inverse association between coffee consumption and endometrial cancer risk. The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) reported that coffee probably protects against endometrial cancer (1). If such a causal association exists, it would have considerable implications. Indeed, after water, coffee and tea are the most commonly consumed beverages in the world. Coffee consumption is especially high in Northern
Downloaded by [Michigan State University] at 03:37 27 February 2015
CAFFEINE AND ENDOMETRIAL CANCER IN WOMEN IN SWEDEN
Europe and North America. Moreover, a great variety of herbal infusions, such as mate, a traditional hot drink in parts of South America, also contain caffeine, a chemical substance present in coffee and tea. Endometrial cancer risk has been previously associated with several host factors, including high body mass index (BMI), nulliparity or low parity, early age at first birth, not using hormonal contraceptives, and use of hormone replacement therapy (in particular estrogens without progestins or with progestins added to estrogens for less than the full treatment cycle). History of type 2 diabetes mellitus (noninsulin dependent), family history of cancer, particularly endometrial cancer, and use of drugs to prevent breast cancer recurrence or de novo breast cancer, such as Tamoxifen, are also associated factors. In addition, endogenous hormone levels have been positively associated with endometrial cancer risk in several prospective cohort studies (2), whereas cigarette smoking decreases risk. Although high BMI has been associated with endometrial cancer risk, no dietary factor has been singled out as being etiologically associated with any certainty (3). Consumption of alcoholic beverages is not associated with endometrial cancer risk (4). An association between coffee or tea consumption and endometrial cancer is biologically plausible, as several active compounds in coffee and tea could have an effect on endogenous hormone levels. Caffeine is one of these compounds, but its effect on endogenous hormones may be modified by BMI (5). Overweight and obese women have a high production of endogenous hormones due to aromatization of androstenedione to estrone in fat tissue. This mechanism is the main explanation for the increased risk of postmenopausal endometrial cancer observed in overweight and obese women (6). Several epidemiological studies have demonstrated an association between type 2 diabetes mellitus and endometrial cancer risk (7–9). Insulin resistance and hyperinsulinemia, conditions that precede type 2 diabetes mellitus, may play a role in the etiology of endometrial cancer (6). Insulin has been shown to stimulate the growth of endometrial stromal cells by binding to insulin receptors on endometrial cells. Insulin may also increase levels of bioactive estrogens by decreasing concentrations of circulating sex hormone binding globulin (6). Coffee consumption may reduce the risk of type 2 diabetes mellitus (10) and lower plasma concentrations of C-peptide, a marker of insulin secretion, among women without type 2 diabetes mellitus (11). Coffee or its compounds may modulate two hormonal factors known to be related to endometrial cancer risk: insulin and estrogen (6), and thus reduce endometrial cancer risk (8,9). The chemical compounds in coffee that may affect carcinogenesis are chlorogenic acids, caffeine, and the coffee diterpenes cafestol and kahweol. We present here prospective data on coffee consumption, black tea consumption, and total caffeine intake, and the incidence of endometrial cancer in women participating in the Swedish Women’s Lifestyle and Health (WLH) cohort study.
1133
Our hypothesis is that coffee and tea consumption and caffeine intake are inversely associated with endometrial cancer incidence in a dose-dependent manner, and that this inverse association is more evident in overweight and obese women (BMI 25), as indicated by Friberg et al. (5), as well as in nonsmokers and never smokers. We also present risk estimates for other potential risk factors.
SUBJECTS AND METHODS Study Population The study cohort and exposure assessment have previously been described in detail (12,13). The source population of this study was comprised of women aged 30–49 years, residing in the Uppsala Health Care Region in Sweden between 1991 and 1992. From this source population, 96,000 women were randomly selected from four age strata (30–34, 35–39, 40–44, and 45–49 years) and were invited to participate in the Swedish component of the Scandinavian WLH cohort study. The women were asked to fill in a questionnaire, which included a food frequency questionnaire (FFQ) component. Of those invited, 49,261 returned the questionnaire and were enrolled in the study. A follow-up questionnaire was completed in 2002–2003 by a subgroup of the enrolled cohort (34,415 women). The Swedish Data Inspection Board and the regional Ethical Committee approved the study. Consent was assumed by the return of the postal questionnaire. We excluded 2694 women, or 10% of the original cohort, from the present analysis as follows: 1483 women who underwent hysterectomy before cohort enrollment, 950 with energy intake outside the 1st (1847 kJ/day) and 99th (12,474 kJ/day) percentiles, nine women with endometrial cancer before enrollment, 244 with breast cancer before cohort enrollment, seven women who had emigrated; and one woman whose questionnaire was considered unreliable due to several contradictory answers. Furthermore, we excluded 4297 women with missing values for the variables used in various analyses (485 of these were missing information on hysterectomy). The remaining 42,270 women were included in most analyses.
Exposure Assessment Coffee consumption was assessed in an open-ended question that asked how many cups per day or per week women consumed during the preceding year. One cup of coffee was estimated to contain 150 g. Tea intake during the preceding year was assessed within the FFQ using 9 prespecified frequencies ranging from never or seldom to three times per day. They also reported the portion size as small, medium or large (0.5, 1, or 1.5 cups). One cup of tea was estimated to contain 200 g. When similar questions were used in a comparable population of women, Spearman correlations between coffee and tea consumption and weighted records for coffee and tea
1134
E. WEIDERPASS ET AL.
Downloaded by [Michigan State University] at 03:37 27 February 2015
were 0.6 and 0.7, respectively (14). Caffeine intake (in g/day) was calculated based on the sum of the estimated amounts of caffeine in coffee and tea (15). In the present analyses, values were set as follows: 69 mg of caffeine per 100 g of coffee; and 25 mg caffeine per 100 g of tea (15). We had no specific information on use of sugar, sweetener, creamers, or milk in coffee or tea in our questionnaire.
Follow-Up The cohort was followed from the date of return of the questionnaires until December 31, 2009 through linkages with the Swedish Cancer Registry, Mortality Registry, and Population Registry (which records migrations). Follow-up time was calculated as the date of entry into the cohort until the occurrence of incident invasive endometrial cancer, emigration, death, incident invasive breast cancer, or the end of the observation period, whichever came first. We censored individuals with a diagnosis of invasive breast cancer during follow-up before endometrial cancer diagnosis, because Tamoxifen use, a risk factor for endometrial cancer, was widespread in Sweden during the follow-up period. We censored women who underwent hysterectomy during follow-up (n D 3457, 8.2% of 42,270 women), identified through linkage with the patient registry (surgery). Hysterectomy 21 days before endometrial cancer diagnosis was not censored as it was assumed the hysterectomy was performed as a result of endometrial cancer. Our outcome was defined as a diagnosis of invasive endometrial cancer (ICD7 D 172.* and 5-digit histological code). Benign tumors (morphology code for ICD-O/2 from 1993 and ICD-O/3 from 2005: 81401 D atypical adenoma, 81402 D a denocarcinoma in situ), tumors classified as unknown if benign, malign, or borderline (morphology code 80701), and nonepithelial endometrial cancers (morphology code 89303 D sarcoma, 89503 D nonepithelial-Mullerian mixed tumor) were not considered. Endometrial tumors were classified as Type 1 (morphology code 81403 D adenocarcinoma and adenocarcinoma not otherwise specified; 814031 D adenocarcinoma, malignant, well differentiated; 814032 D adenocarcinoma, malignant, moderately differentiated; 838031 D endometrioid adenocarcinoma well differentiated; and malign. with missing code) and Type 2 (84603 D papillary serous cystadenocarcinoma; 814033 D adenocarcinoma, malignant, poorly differentiated; 80203 D carcinoma, malign, undifferentiated; 84603 D papillary serous cystadenocarcinoma). Type 2 endometrial cancers were censored in the analysis as the characteristics are different between histological subtypes (Type 1 and 2) and Type 2 is very rare (only 5 incident cases in the study population).
Covariables We adjusted for the potential confounding effect of the following covariables assessed in the baseline questionnaire: BMI (weight in kg divided by height in m2 at cohort enrollment as a
continuous variable and categorized as
