Coffee and Green Tea Consumption and Subsequent Risk of Malignant Lymphoma and Multiple Myeloma in Japan: The Japan Public Health Center-based Prospective Study

Several studies suggested that coffee and green tea consumption may decrease the risk of some types of cancers (1, 2). However, epidemiologic evidence for this protective effect on malignant lymphoma and multiple myeloma is scarce. Here, we investigated the association between coffee and green tea consumption and the risk of malignant lymphoma and multiple myeloma in a large-scale population-based cohort study in Japan.

The details of study design of the Japan Public Health Center–based Prospective Study have been detailed elsewhere (3). Briefly, the study was launched in 1990 for cohort I and in 1993 for cohort II. Cohort I covered five prefectural public health center (PHC) areas (Iwate, Akita, Nagano, Okinawa-Chubu, and Tokyo) and cohort II covered six (Ibaraki, Niigata, Kochi, Nagasaki, Okinawa-Miyako, and Osaka). A baseline self-administered questionnaire survey on various life-style factors, including coffee and green tea consumption, was conducted in 1990 for cohort I and in 1993 to 1994 for cohort II, with a high response rate (81%). In the current analysis, all subjects in one public health center area (Tokyo) were excluded because their incidence data were not available, and some subjects in another area (Suita, Osaka) were also excluded because different definitions of the study population had been applied. We further excluded participants met the following exclusion criteria: (i) non-Japanese nationality; (ii) late report of emigration before the start of the follow-up period; (iii) incorrect birth date; (iv) duplicate registration; (v) later withdrawal of consent; (vi) self-reported history of cancer at baseline survey; (vii) missing values for coffee or green tea consumption. Finally, a total of 95,807 Japanese subjects (45,937 men and 49,870 women; age 40–69 years at baseline) who completed a questionnaire about their coffee and green tea consumption were included in this analysis. The study protocol was approved by the institutional review boards of the National Cancer Center, Japan, and Aichi Cancer Center Research Institute.

Cancers were identified by active patient notification from major local hospitals in the study area and by data collection from population-based cancer registries with approval. Information on the cause of death was supplemented by checking death certificate files with permission. Malignant lymphoma and multiple myeloma were coded using the International Classification of Diseases for Oncology, Third Edition (4). Malignant lymphoma (morphology code: 959–9729823) and multiple myeloma (9732) were included in the current analysis.

Exposure data are based on a baseline self-administered questionnaire survey about various health habits, including coffee and green tea consumption and other lifestyle factors. Information on coffee and green tea consumption was obtained in terms of the frequency and amount of each beverage consumed according to the following categories: hardly ever, 1–2 d/wk, 3–4 d/wk and almost daily (further divided into 1–2 cups/day, 3–4 cups/day or 5 cups/day). For the current analysis, we further grouped these categories based on their distribution among the subjects (coffee consumption: almost none, 1–4 times/week, 1–2 cups/day, ≥3 cups/day and green tea consumption: almost none, 1–4 times/week, 1–2 cups/day, 3–4 cups/day, ≥5 cups/day).

Person-years of follow-up from the date of baseline survey were calculated until the date of diagnosis of malignant lymphoma or multiple myeloma, date of death, move from the PHC area, or December 31, 2012, whichever occurred first. Multivariate-adjusted HRs and 95% confidence intervals (CI) of malignant lymphoma and multiple myeloma were calculated for coffee consumption (almost none, 1–4 times/week, 1–2 cups/day, ≥3 cups/day) and green tea consumption (almost none, 1–4 times/week, 1–2 cups/day, 3–4 cups/day, ≥5 cups/day) at baseline by a Cox proportional hazards model. We also evaluated the P value for trend by assignment of ordinal variables in each category. We estimated two types of HR: (i) adjusted for age at baseline (continuous), gender (men or women) and study area (10 PHC areas); and (ii) further adjusted for smoking status (never, former, and current smoker), alcohol consumption (nondrinkers, occasional drinkers, <300 ethanol intake/week and ≥300 ethanol intake/week), body mass index (<18.5, 18.5–24.9, 25–29.9, and ≥30 kg/m²), and occupation (professional or office worker, sales clerk or other, farmer, manual laborer, unemployed, and missing). All statistical analyses were done using Stata version 13.1 software (Stata Corp.), with a P value <0.05 considered to be statistically significant.

During the follow-up period (average, 18.3 years), a total of 411 malignant lymphoma cases and 138 multiple myeloma cases were identified. Table 1 shows the baseline characteristics of study subjects according to coffee and green tea consumption at baseline. Both men and women with high coffee consumption were more likely to be smokers and tended to be younger than those who hardly drank. On the other hand, both men and women with higher green tea tended to be older.

Table 2 shows the adjusted HRs for malignant lymphoma and multiple myeloma in relation to coffee and green tea consumption. Overall, we observed no significant association between coffee or green tea consumption and the risk of malignant lymphoma for both sexes. Similarly, we observed no significant association with the risk of multiple myeloma for both sexes.

In this large Japanese population-based cohort study, we observed no significant association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma.

Consistent with our results, a recent meta-analysis has reported that there was no sufficient evidence to support an association between coffee consumption and the risk of malignant lymphoma, with a pooled relative risk for coffee drinker relative to non/occasional drinker of 1.05 (95% CI, 0.89–1.23; ref. 5). In addition, a few studies investigated the association between coffee consumption and the risk of multiple myeloma, but no study showed a significant association. In contrast, two studies reported that green tea consumption reduced the risk of malignant lymphoma and multiple myeloma. The Ohsaki Study, a population-based cohort study in Japan which involved 41,761 participants and 119 lymphoid neoplasm cases, reported that green tea consumption was inversely associated with the risk of lymphoid neoplasms, including malignant lymphoma and multiple myeloma (≥5 cups/day vs. <1 cup/day; HR, 0.52; 95% CI, 0.31–0.87; ref. 6). A case-control study of 220 multiple myeloma cases and 220 controls in Northwest China also reported that green tea was significantly associated with a reduced risk of multiple myeloma (>1 times/month vs. never; OR, 0.38; 95% CI, 0.27–0.53; ref. 7). Inconsistency with our finding might be from modest sample size or retrospective design.

In summary, our results do not support an association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma. Further research is needed to confirm our results.

M. Inoue is the beneficiary of a financial contribution from the AXA Research fund as chair holder of the AXA Department of Health and Human Security, Graduate School of Medicine, The University of Tokyo. No potential conflicts of interest were disclosed by the other authors.

The AXA Research Fund had no role in the design of the study, data collection, analysis, interpretation, or manuscript drafting, or in the decision to submit the manuscript for publication.

Conception and design: T. Ugai, K. Matsuo, M. Inoue, S. Tsugane

Development of methodology: K. Matsuo, M. Inoue

Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): N. Sawada, M. Iwasaki, T. Shimazu, M. Inoue, S. Tsugane

Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): T. Ugai, K. Matsuo, M. Iwasaki, T. Shimazu, S. Tsugane

Writing, review, and/or revision of the manuscript: T. Ugai, K. Matsuo, M. Iwasaki, T. Yamaji, T. Shimazu, S. Sasazuki, M. Inoue, Y. Kanda, S. Tsugane

Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): K. Matsuo, N. Sawada, S. Tsugane

Study supervision: K. Matsuo, S. Tsugane

We are indebted to the Aomori, Akita, Iwate, Ibaraki, Niigata, Osaka, Kochi, Nagasaki, and Okinawa Cancer Registries for providing their incidence data. Members of the Japan Public Health Center-based Prospective Study (JPHC Study, principal investigator: S. Tsugane) Group are: S. Tsugane, N. Sawada, M. Iwasaki, S. Sasazuki, T. Yamaji, T. Shimazu and T. Hanaoka, National Cancer Center, Tokyo; J. Ogata, S. Baba, T. Mannami, A.Okayama, and Y. Kokubo, National Cerebral and Cardiovascular Center, Osaka; K. Miyakawa, F. Saito, A. Koizumi, Y. Sano, I. Hashimoto, T. Ikuta, Y. Tanaba, H. Sato, Y. Roppongi, T. Takashima and H. Suzuki, Iwate Prefectural Ninohe Public Health Center, Iwate; Y. Miyajima, N. Suzuki, S. Nagasawa, Y. Furusugi, N. Nagai, Y. Ito, S. Komatsu and T. Minamizono, Akita Prefectural Yokote Public Health Center, Akita; H. Sanada, Y. Hatayama, F. Kobayashi, H. Uchino, Y. Shirai, T. Kondo, R. Sasaki, Y. Watanabe, Y. Miyagawa, Y. Kobayashi, M. Machida, K. Kobayashi and M. Tsukada, Nagano Prefectural Saku Public Health Center, Nagano; Y. Kishimoto, E. Takara, T. Fukuyama, M. Kinjo, M. Irei, and H. Sakiyama, Okinawa Prefectural Chubu Public Health Center, Okinawa; K. Imoto, H. Yazawa, T. Seo, A. Seiko, F. Ito, F. Shoji and R. Saito, Katsushika Public Health Center, Tokyo; A. Murata, K. Minato, K. Motegi, T. Fujieda and S. Yamato, Ibaraki Prefectural Mito Public Health Center, Ibaraki; K. Matsui, T. Abe, M. Katagiri, M. Suzuki, and K. Matsui, Niigata Prefectural Kashiwazaki and Nagaoka Public Health Center, Niigata; M. Doi, A. Terao, Y. Ishikawa, and T. Tagami, Kochi Prefectural Chuo-higashi Public Health Center, Kochi; H. Sueta, H. Doi, M. Urata, N. Okamoto, F. Ide, H. Goto and R Fujita, Nagasaki Prefectural Kamigoto Public Health Center, Nagasaki; H. Sakiyama, N. Onga, H. Takaesu, M. Uehara, T. Nakasone and M. Yamakawa, Okinawa Prefectural Miyako Public Health Center, Okinawa; F. Horii, I. Asano, H. Yamaguchi, K. Aoki, S. Maruyama, M. Ichii, and M. Takano, Osaka Prefectural Suita Public Health Center, Osaka; Y. Tsubono, Tohoku University, Miyagi; K. Suzuki, Research Institute for Brain and Blood Vessels Akita, Akita; Y. Honda, K. Yamagishi, S. Sakurai and N. Tsuchiya, University of Tsukuba, Ibaraki; M. Kabuto, National Institute for Environmental Studies, Ibaraki; M. Yamaguchi, Y. Matsumura, S. Sasaki, and S. Watanabe, National Institute of Health and Nutrition, Tokyo; M. Akabane, Tokyo University of Agriculture, Tokyo; T. Kadowaki and M. Inoue, The University of Tokyo, Tokyo; M. Noda and T. Mizoue, National Center for Global Health and Medicine, Tokyo; Y. Kawaguchi, Tokyo Medical and Dental University, Tokyo; Y. Takashima and Y. Yoshida, Kyorin University, Tokyo; K. Nakamura and R. Takachi, Niigata University, Niigata; J. Ishihara, Sagami Women's University, Kanagawa; S. Matsushima and S. Natsukawa, Saku General Hospital, Nagano; H. Shimizu, Sakihae Institute, Gifu; H. Sugimura, Hamamatsu University School of Medicine, Shizuoka; S. Tominaga, Aichi Cancer Center, Aichi; N. Hamajima, Nagoya University, Aichi; H. Iso and T. Sobue, Osaka University, Osaka; M. Iida, W. Ajiki, and A. Ioka, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka; S. Sato, Chiba Prefectural Institute of Public Health, Chiba; E. Maruyama, Kobe University, Hyogo; M. Konishi, K. Okada, and I. Saito, Ehime University, Ehime; N. Yasuda, Kochi University, Kochi; S. Kono, Kyushu University, Fukuoka; S. Akiba, Kagoshima University, Kagoshima; T. Isobe, Keio University, Tokyo; Y. Sato, Tokyo Gakugei University, Tokyo.

This study was supported by National Cancer Center Research and Development Fund [23-A-31(toku) and 26-A-2; since 2011] and a Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan (from 1989 to 2010).