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Smoking and Pancreatic Cancer Incidence: a & Prevention Pooled Analysis of 10 Population-Based Cohort Studies in Japan Yuriko N

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Smoking and Pancreatic Cancer Incidence: a & Prevention Pooled Analysis of 10 Population-Based Cohort Studies in Japan Yuriko N Published OnlineFirst May 21, 2019; DOI: 10.1158/1055-9965.EPI-18-1327 Research Article Cancer Epidemiology, Biomarkers Smoking and Pancreatic Cancer Incidence: A & Prevention Pooled Analysis of 10 Population-Based Cohort Studies in Japan Yuriko N. Koyanagi1, Hidemi Ito1,2, Keitaro Matsuo2,3, Yumi Sugawara4, Akihisa Hidaka5, Norie Sawada5, Keiko Wada6, Chisato Nagata6, Akiko Tamakoshi7, Yingsong Lin8, Taro Takeuchi9, Yuri Kitamura9, Mai Utada10, Atsuko Sadakane10, Tetsuya Mizoue11, Mariko Naito12, Keitaro Tanaka13,Taichi Shimazu5, Shoichiro Tsugane5, and Manami Inoue5, for the Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan Abstract Background: Detailed prospective evaluation of cigarette former smoking and small cumulative dose of 20 pack-years smoking associated with pancreatic cancer risk in large Asian (PY) were observed only among females, regardless of envi- populations is limited. The aim of this study was to examine ronmental tobacco smoke exposure. Trend analysis indicated this association in a Japanese population, with a particular significant 6% and nonsignificant 6% increases in pancreatic focus on evaluating sex differences. cancer risk for every 10 PYs in males and females, respectively. Methods: We performed a pooled analysis of 10 population- Risk became comparable with never smokers after 5 years of based cohort studies. We calculated study-specific HRs and smoking cessation in males. In females, however, we observed 95% confidence intervals (CI) using Cox proportional hazards no risk attenuation by smoking cessation. regression, and then estimated summary HRs by pooling these Conclusions: This study supports the well-known associa- estimates with a random effects model. tion between smoking and pancreatic cancer and indicates Results: During 4,695,593 person-years of follow-up in potential sex differences in a Japanese population. Quitting 354,154 participants, 1,779 incident pancreatic cancer cases smoking would be beneficial for pancreatic cancer prevention, were identified. We observed an increased pancreatic cancer especially in males. risk for current smoking compared with never smoking in Impact: Pancreatic cancer risk is increased with cumulative both males [HR (95% CI), 1.59 (1.32–1.91)] and females [HR smoking exposure and decreased with smoking cessation, with (95% CI), 1.81 (1.43–2.30)]. Significant risk elevations for potential sex differences. Introduction diagnosed in the advanced stages, which contributes to a 5-year survival rate of only 7.7% (3). Identifying modifiable risk factors Pancreatic cancer is the fourth leading cause of cancer-related for the primary prevention of pancreatic cancer is therefore of the death in developed countries (1). In Japan, pancreatic cancer was utmost importance. ranked the seventh most common cancer in 2014, with 36,156 The International Agency for Research on Cancer (IARC) con- new cases, and the fourth most frequent cause of cancer-related cluded that smoking is one of the most important modifiable death in 2017, with 34,224 deaths (2). Because the early stages of risk factors for pancreatic cancer (4). In a meta-analysis of 82 pancreatic cancer do not usually produce symptoms and an early independent studies (42 case–control, 35 cohort, and five nested detection method has yet to be established, this cancer is generally 1Division of Cancer Information and Control, Department of Preventive Medicine, 12Department of Oral Epidemiology, Hiroshima University Graduate School of Aichi Cancer Research Institute, Nagoya, Japan. 2Department of Epidemiology, Biomedical and Health Sciences, Hiroshima, Japan. 13Department of Preventive Nagoya University Graduate School of Medicine, Nagoya, Japan. 3Division of Medicine, Faculty of Medicine, Saga University, Saga, Japan. Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan. 4Division of Epidemiology, Note: Supplementary data for this article are available at Cancer Epidemiology, Department of Health Informatics and Public Health, Tohoku University School Biomarkers & Prevention Online (http://cebp.aacrjournals.org/). of Public Health, Graduate School of Medicine, Sendai, Japan. 5Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Corresponding Author: Hidemi Ito, Aichi Cancer Research Institute, 1-1 Tokyo, Japan. 6Department of Epidemiology and Preventive Medicine, Gifu Kanokoden, Chikusa-ku, Nagoya, Aichi 4648681, Japan. Phone: 815-2762-6111; University Graduate School of Medicine, Gifu, Japan. 7Department of Public Fax: 815-2763-5233; E-mail: [email protected] Health, Hokkaido University Faculty of Medicine, Sapporo, Japan. 8Department of Public Health, Aichi Medical University School of Medicine, Aichi, Japan. Cancer Epidemiol Biomarkers Prev 2019;28:1370–8 9Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. 10Department of Epidemiology, Radiation doi: 10.1158/1055-9965.EPI-18-1327 Effects Research Foundation, Hiroshima, Japan. 11Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan. Ó2019 American Association for Cancer Research. 1370 Cancer Epidemiol Biomarkers Prev; 28(8) August 2019 Downloaded from cebp.aacrjournals.org on September 24, 2021. © 2019 American Association for Cancer Research. Published OnlineFirst May 21, 2019; DOI: 10.1158/1055-9965.EPI-18-1327 Pooled Analysis of Smoking and Pancreatic Cancer in Japan case–control studies) published between 1950 and 2007, the the Three-Prefecture Cohort Study in Osaka (OSAKA; ref. 22), and summary risks for current and former smokers relative to never the Life Span Study (LSS; ref. 24; Table 1). Participants with a past smokers were 1.74 [95% confidence interval (CI), 1.61–1.87] and history of cancer at baseline, those without information on 1.20 (95% CI, 1.11–1.29), respectively (5). A second meta- smoking, and those with estimated radiation doses from the analysis of 11 cohort studies published between 2000 and atomic bombing of 100 mGy (for LSS) were excluded from 2016 reported similar significant risk elevations of 66% for the analyses. Each study was reviewed and approved by its current smokers and 40% for former smokers (6). To date, a total relevant institutional ethics review board. of five prospective studies have evaluated the association between Four studies (JPHC-I and -II, JACC, and TAKAYAMA) have pancreatic cancer risk and smoking status using data from a already published results on the association of smoking with Japanese population (7–12), all of which confirmed a significant pancreatic cancer risk in their respective cohorts (7, 8, 10, 12). We risk elevation in current smokers in at least one sex. Furthermore, a reanalyzed the results of each study using the updated dataset in recent meta-analysis of three case–control and four cohort studies this study. in Japan reported a summary estimate for ever smoking of 1.68 (95% CI, 1.38–2.05; ref. 13), which is comparable with the results Assessment of exposure of meta- and pooled analyses (5, 6, 9, 11, 14, 15). In each study, smoking status, cumulative smoking exposure, In addition to smoking status, studies have also evaluated the and years of smoking cessation were assessed using a self- association of pancreatic cancer with the intensity and duration of administered questionnaire at baseline. For smoking status, sub- cigarette smoking. Several meta- and pooled analyses have pro- jects were categorized into three groups, including never smokers, vided clear evidence that risk increases significantly with increas- former smokers, and current smokers. Cumulative smoking expo- ing daily cigarette consumption, duration of smoking, and pack- sure was evaluated by PYs, defined as the number of packs smoked years (PY; refs. 5, 11, 14, 16). Moreover, risk in former smokers per day (or the number of cigarettes smoked per day divided by decreases to the same level as that in never smokers within 10– 20) multiplied by the number of years of smoking. Subjects were 20 years of cessation (5, 14–16). These findings were mainly then classified into five groups for males: 0 (never smokers), derived from Western populations, however, and prospective >0–20, >20–40, >40–60, and >60; and four groups for females: evidence on the association of pancreatic cancer incidence with 0, >0–20, >20–40, and >40. Subjects were then additionally the intensity and duration of smoking and years of smoking classified into five groups by smoking status: never smokers, cessation from substantial Asian populations remains limited, former smokers, and current smokers with >0–20, >20–40, or especially among females. There have been three prospective >40 PYs. To evaluate the impact of smoking cessation, subjects studies (7, 8, 10, 12) evaluating the intensity and duration of were classified into five groups: never smokers, former smokers smoking and two studies (7, 17) evaluating years of smoking with 10, 5–9, or 0–4 years of smoking cessation, and current cessation in Japanese populations, but detailed evaluations smokers. Important covariates for pancreatic cancer, including among females using the same categories as males were not body mass index (BMI), alcohol consumption, history of diabe- conducted, mainly due to the small sample size of former or tes, and environmental tobacco smoke (ETS) exposure were also current smokers among females in Japan. Moreover, the relation- collected via a self-administered
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