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Pancreatic Neoplasms: HELP
Articles by Keitaro Matsuo
Based on 18 articles published since 2009
(Why 18 articles?)
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Between 2009 and 2019, Keitaro Matsuo wrote the following 18 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Cigarette smoking and pancreas cancer risk: an evaluation based on a systematic review of epidemiologic evidence in the Japanese population. 2011

Matsuo, Keitaro / Ito, Hidemi / Wakai, Kenji / Nagata, Chisato / Mizoue, Tetsuya / Tanaka, Keitaro / Tsuji, Ichiro / Tamakoshi, Akiko / Sasazuki, Shizuka / Inoue, Manami / Tsugane, Shoichiro / Anonymous90707. ·Division of Epidemiology and Prevention, Aichi cancer Center Research Institute, Nagoya, Japan. kmatsuo@aichi-cc.jp ·Jpn J Clin Oncol · Pubmed #21971423.

ABSTRACT: OBJECTIVE: Cigarette smoking has been recognized as an important risk factor for pancreas cancer, but the magnitude of the association may vary among geographical areas. Therefore, we reviewed epidemiologic studies on the association between cigarette smoking and pancreas cancer in the Japanese population. METHODS: Original data were obtained from MEDLINE searched using PubMed or from searches of the Ichushi database, complemented with manual searches. Evaluation of associations was based on the strength of evidence ('convincing', 'probable', 'possible' or 'insufficient') and the magnitude of association ('strong', 'moderate', 'weak' or 'no association'), together with biological plausibility as previously evaluated by the International Agency of Research on Cancer. RESULTS: We identified four cohort studies and three case-control studies. All cohort studies consistently showed positive associations between pancreas cancer and cigarette smoking, although statistical significance in each study is variable. Most of the cohort studies consistently showed that cigarette smoking had a dose-response relationship with pancreas cancer. One case-control study showed a strong positive association, but the rest did not show any association. Meta-analysis of seven studies indicated that a summary estimate for ever smoking relative to never smoking was 1.68 (95% confidence interval: 1.38-2.05). CONCLUSIONS: We conclude that there is convincing evidence that cigarette smoking moderately increases the risk of pancreas cancer in the Japanese population.

2 Article Surgery for Pancreatic Neuroendocrine Tumor G3 and Carcinoma G3 Should be Considered Separately. 2019

Yoshida, Tsukasa / Hijioka, Susumu / Hosoda, Waki / Ueno, Makoto / Furukawa, Masayuki / Kobayashi, Noritoshi / Ikeda, Masafumi / Ito, Tetsuhide / Kodama, Yuzo / Morizane, Chigusa / Notohara, Kenji / Taguchi, Hiroki / Kitano, Masayuki / Yane, Kei / Tsuchiya, Yoshiaki / Komoto, Izumi / Tanaka, Hiroki / Tsuji, Akihito / Hashigo, Syunpei / Mine, Tetsuya / Kanno, Atsushi / Murohisa, Go / Miyabe, Katsuyuki / Takagi, Tadayuki / Matayoshi, Nobutaka / Sakaguchi, Masafumi / Ishii, Hiroshi / Kojima, Yasushi / Matsuo, Keitaro / Yoshitomi, Hideyuki / Nakamori, Shoji / Yanagimoto, Hiroaki / Yatabe, Yasushi / Furuse, Junji / Mizuno, Nobumasa. ·Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Department of Gastroenterology, Kizawa Memorial Hospital, Minokamo, Japan. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. shijioka@ncc.go.jp. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. shijioka@ncc.go.jp. · Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Division of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, Yokohama, Japan. · Department of Hepato-Biliary-Pancreatology, National Kyushu Cancer Center, Fukuoka, Japan. · Department of Oncology, Yokohama City University Hospital, Yokohama, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. · Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan. · Department of Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. · Department of Gastroenterology and Hepatology, Kinki University, Faculty of Medicine, Sayama, Japan. · Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan. · Department of Digestive Surgery, Niigata Cancer Center Hospital, Niigata, Japan. · Department of Surgery, Kansai Electric Power Hospital, Osaka, Japan. · Department of Gastroenterology, Suzuka General Hospital, Suzuka, Japan. · Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan. · Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. · Department of Gastroenterology, Tokai University School of Medicine, Isehara, Japan. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. · Department of Gastroenterology, Seirei Hamamatsu General Hospital, Hamamatsu, Japan. · Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. · Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan. · Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. · Department of Gastroenterology, Saiseikai Kumamoto Hospital, Kumamoto, Japan. · Department of Gastroenterology, Shikoku Cancer Center, Matsuyama, Japan. · Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. · Department of Gastroenterology, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan. · Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan. · Department of General Surgery, Chiba University, Graduate School of Medicine, Chiba, Japan. · Department of Hepato-biliary-Pancreatic Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan. · Department of Surgery, Kansai Medical University Hospital, Maikata, Japan. · Department of Medical Oncology, Kyorin University Faculty of Medicine, Mitaka, Japan. ·Ann Surg Oncol · Pubmed #30863939.

ABSTRACT: BACKGROUND: The role of surgery in pancreatic neuroendocrine neoplasm grade 3 (pNEN-G3) treatment remains unclear. We aimed to clarify the role of surgery for pNEN-G3, which has recently been reclassified as pancreatic neuroendocrine tumor-G3 (pNET-G3) and pancreatic neuroendocrine carcinoma-G3 (pNEC-G3), with and without metastases, respectively. METHODS: We analyzed a subgroup of patients from the Japanese pancreatic NEC study, a Japanese multicenter case-series study of pNEN-G3. Pathologists subclassified 67 patients as having pNET-G3 or pNEC-G3 based on morphological features. We compared the overall survival (OS) rates among patients who were grouped according to whether they had undergone tumor-targeted surgery for tumors without (SwoM) or with (SwM) metastases, or non-surgical procedures (NS). RESULTS: Data from 21 patients with pNET-G3 (SwoM, n = 6; SwM, n = 5; NS, n = 10) and 46 patients with pNEC-G3 (SwoM, n = 8; SwM, n = 5; NS, n = 33) were analyzed. OS of patients with pNET-G3 was significantly longer after SwoM and SwM than with NS (p = 0.018 and p = 0.022). In contrast, OS did not significantly differ between either SwoM or SwM and NS (p = 0.093 and p = 0.489) among patients with pNEC-G3. CONCLUSION: The role of surgery should be considered separately for pNET-G3 and pNEC-G3. Although SwoM and SwM can be considered for pNET-G3, caution is advised before considering SwM and SwoM for pNEC-G3.

3 Article Conversion surgery only for highly selected patients with unresectable pancreatic cancer: a satisfactory outcome in exchange for a lower resection rate. 2019

Natsume, Seiji / Shimizu, Yasuhiro / Senda, Yoshiki / Hijioka, Susumu / Matsuo, Keitaro / Ito, Seiji / Komori, Koji / Abe, Tetsuya / Hara, Kazuo. ·Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Kanokoden 1-1, Chikusa-ku, Nagoya, Japan. snatsume@aichi-cc.jp. · Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Kanokoden 1-1, Chikusa-ku, Nagoya, Japan. · Department of Gastroenterology, Aichi Cancer Center Hospital, Kanokoden 1-1, Chikusa-ku, Nagoya, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-Ku, Tokyo, Japan. · Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Kanokoden 1-1, Chikusa-ku, Nagoya, Japan. ·Surg Today · Pubmed #30730003.

ABSTRACT: PURPOSE: The purpose of this study is to clarify the resection rate, safety, and significance of conversion surgery for highly selected patients with unresectable pancreatic cancer (URPca). METHODS: We studied 434 URPca patients. Conversion surgery was permitted only for patients who met following requirements: responders to first-line therapy, showing sufficient reduction of the local tumor to enable complete resection, at least 6 months of disease control, and no metastatic lesions detected on radiological examinations (for patients with metastatic disease). The overall survival (OS) was compared between patients who underwent surgery and those who did not. Furthermore, a multivariate analysis was performed to identify possible predictive factors for both total patients with URPca and responders. RESULTS: Conversion surgery was performed in 18 patients (4.1%). The pathologically complete resection rate was 88.9% (16/18). The median operative time, blood loss, and hospitalization duration were 450 min, 780 ml, and 29 days, respectively. The OS was significantly better in patients who underwent surgery than in those who did not. In a multivariate analysis, conversion surgery was shown to be significantly correlated with the OS both in total patients and responders. CONCLUSIONS: A satisfactory outcome was achieved for highly selected patients with URPca in exchange for a lower resection rate (4.1%).

4 Article Prediction model for pancreatic cancer risk in the general Japanese population. 2018

Nakatochi, Masahiro / Lin, Yingsong / Ito, Hidemi / Hara, Kazuo / Kinoshita, Fumie / Kobayashi, Yumiko / Ishii, Hiroshi / Ozaka, Masato / Sasaki, Takashi / Sasahira, Naoki / Morimoto, Manabu / Kobayashi, Satoshi / Ueno, Makoto / Ohkawa, Shinichi / Egawa, Naoto / Kuruma, Sawako / Mori, Mitsuru / Nakao, Haruhisa / Wang, Chaochen / Nishiyama, Takeshi / Kawaguchi, Takahisa / Takahashi, Meiko / Matsuda, Fumihiko / Kikuchi, Shogo / Matsuo, Keitaro. ·Division of Data Science, Data Coordinating Center, Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan. · Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Japan. · Division of Cancer Information and Control, Aichi Cancer Center Research Institute, Nagoya, Japan. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Clinical Research Center, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. · Department of Hepato-biliary-pancreatic Medicine, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. · Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center Hospital, Kanagawa, Japan. · Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan. · Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan. · Hokkaido Chitose College of Rehabilitation, Hokkaido, Japan. · Division of Hepatology and Pancreatology, Aichi Medical University School of Medicine, Nagakute, Japan. · Department of Public Health, Nagoya City University Graduate School of Medicine, Nagoya, Japan. · Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. · Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan. ·PLoS One · Pubmed #30192808.

ABSTRACT: Genome-wide association studies (GWASs) have identified many single nucleotide polymorphisms (SNPs) that are significantly associated with pancreatic cancer susceptibility. We sought to replicate the associations of 61 GWAS-identified SNPs at 42 loci with pancreatic cancer in Japanese and to develop a risk model for the identification of individuals at high risk for pancreatic cancer development in the general Japanese population. The model was based on data including directly determined or imputed SNP genotypes for 664 pancreatic cancer case and 664 age- and sex-matched control subjects. Stepwise logistic regression uncovered five GWAS-identified SNPs at five loci that also showed significant associations in our case-control cohort. These five SNPs were included in the risk model and also applied to calculation of the polygenic risk score (PRS). The area under the curve determined with the leave-one-out cross-validation method was 0.63 (95% confidence interval, 0.60-0.66) or 0.61 (0.58-0.64) for versions of the model that did or did not include cigarette smoking and family history of pancreatic cancer in addition to the five SNPs, respectively. Individuals in the lowest and highest quintiles for the PRS had odds ratios of 0.62 (0.42-0.91) and 1.98 (1.42-2.76), respectively, for pancreatic cancer development compared with those in the middle quintile. We have thus developed a risk model for pancreatic cancer that showed moderately good discriminatory ability with regard to differentiation of pancreatic cancer patients from control individuals. Our findings suggest the potential utility of a risk model that incorporates replicated GWAS-identified SNPs and established demographic or environmental factors for the identification of individuals at increased risk for pancreatic cancer development.

5 Article Body-Mass Index and Pancreatic Cancer Incidence: A Pooled Analysis of Nine Population-Based Cohort Studies With More Than 340,000 Japanese Subjects. 2018

Koyanagi, Yuriko N / Matsuo, Keitaro / Ito, Hidemi / Tamakoshi, Akiko / Sugawara, Yumi / Hidaka, Akihisa / Wada, Keiko / Oze, Isao / Kitamura, Yuri / Liu, Rong / Mizoue, Tetsuya / Sawada, Norie / Nagata, Chisato / Wakai, Kenji / Nakayama, Tomio / Sadakane, Atsuko / Tanaka, Keitaro / Inoue, Manami / Tsugane, Shoichiro / Sasazuki, Shizuka. ·Department of Epidemiology, Nagoya University Graduate School of Medicine. · Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute. · Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute. · Department of Public Health, Hokkaido University Graduate School of Medicine. · Division of Epidemiology, Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine. · Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center. · Department of Epidemiology and Preventive Medicine, Gifu University Graduate School of Medicine. · Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine. · Department of Epidemiology and International Health, International Clinical Research Center, National Center for Global Health and Medicine. · Department of Preventive Medicine, Nagoya University Graduate School of Medicine. · Center for Cancer Control and Statistics, Osaka Medical Center for Cancer and Cardiovascular Diseases. · Department of Epidemiology, Radiation Effects Research Foundation. · Department of Preventive Medicine, Faculty of Medicine, Saga University. · AXA Department of Health and Human Security, Graduate School of Medicine, University of Tokyo. ·J Epidemiol · Pubmed #29225297.

ABSTRACT: BACKGROUND: A high body mass index (BMI) has been proposed as an important risk factor for pancreatic cancer. However, this association of BMI with pancreatic cancer risk has not been confirmed in Asian populations. METHODS: We evaluated the association between BMI (either at baseline or during early adulthood) and pancreatic cancer risk by conducting a pooled analysis of nine population-based prospective cohort studies in Japan with more than 340,000 subjects. Summary hazard ratios (HRs) were estimated by pooling study-specific HRs for unified BMI categories with a random-effects model. RESULTS: Among Japanese men, being obese at baseline was associated with a higher risk of pancreatic cancer incidence (≥30 kg/m CONCLUSIONS: Pooling of data from cohort studies with a considerable number of Japanese subjects revealed a significant positive association between obesity and pancreatic cancer risk among men. This information indicates that strategies that effectively prevent obesity among men might lead to a reduced burden of pancreatic cancer, especially in Asian populations.

6 Article Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation. 2018

Campa, Daniele / Pastore, Manuela / Capurso, Gabriele / Hackert, Thilo / Di Leo, Milena / Izbicki, Jakob R / Khaw, Kay-Tee / Gioffreda, Domenica / Kupcinskas, Juozas / Pasquali, Claudio / Macinga, Peter / Kaaks, Rudolf / Stigliano, Serena / Peeters, Petra H / Key, Timothy J / Talar-Wojnarowska, Renata / Vodicka, Pavel / Valente, Roberto / Vashist, Yogesh K / Salvia, Roberto / Papaconstantinou, Ioannis / Shimizu, Yasuhiro / Valsuani, Chiara / Zambon, Carlo Federico / Gazouli, Maria / Valantiene, Irena / Niesen, Willem / Mohelnikova-Duchonova, Beatrice / Hara, Kazuo / Soucek, Pavel / Malecka-Panas, Ewa / Bueno-de-Mesquita, H B As / Johnson, Theron / Brenner, Herman / Tavano, Francesca / Fogar, Paola / Ito, Hidemi / Sperti, Cosimo / Butterbach, Katja / Latiano, Anna / Andriulli, Angelo / Cavestro, Giulia Martina / Busch, Olivier R C / Dijk, Frederike / Greenhalf, William / Matsuo, Keitaro / Lombardo, Carlo / Strobel, Oliver / König, Anna-Katharina / Cuk, Katarina / Strothmann, Hendrik / Katzke, Verena / Cantore, Maurizio / Mambrini, Andrea / Oliverius, Martin / Pezzilli, Raffaele / Landi, Stefano / Canzian, Federico. ·Department of Biology, University of Pisa, Pisa, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Digestive and Liver Disease Unit, S. Andrea Hospital 'Sapienza' University of Rome, Rome, Italy. · Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy. · Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Clinical Gerontology Unit, Addenbrooke's Hospital, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom. · Division of Gastroenterology and Research Laboratory, Department of Surgery, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy. · Institute of Experimental Medicine, Czech Academy of Sciences and Institute of Clinical and Experimental Medicine, Prague, Czech Republic. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. · MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Department of Visceral Surgery, Kantonsspital Aarau AG, Aarau, Switzerland. · Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Second Department of Surgery, Aretaieion Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. · Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan. · Oncological Department, Azienda USL Toscana Nord Ovest, Oncological Unit of Massa Carrara, Carrara, Massa and Carrara, Italy. · Department of Medicine (DIMED), University of Padova, Padova, Italy. · Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. · Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment, Bilthoven, The Netherlands. · Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, St Mary's Campus, London, United Kingdom. · Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Division of Clinical Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Preventive Oncology, German Cancer Research Center (DKFZ), and National Center for Tumor Diseases (NCT), Heidelberg, Germany. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy. · Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan. · Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan. · Department of Surgery, Academic Medical Centre, Amsterdam, the Netherlands. · Department of Pathology, Academic Medical Centre, Amsterdam, the Netherlands. · Institute for Health Research, Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Division of General and Transplant Surgery, University of Pisa, Pisa, Italy. · Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, University of Pisa, Pisa, Italy. · Transplant Surgery Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. · Pancreas Unit, Department of Digestive Diseases and Internal Medicine Sant'Orsola-Malpighi Hospital, Bologna, Italy. ·Int J Cancer · Pubmed #28913878.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (OR

7 Article Rb Loss and 2017

Hijioka, Susumu / Hosoda, Waki / Matsuo, Keitaro / Ueno, Makoto / Furukawa, Masayuki / Yoshitomi, Hideyuki / Kobayashi, Noritoshi / Ikeda, Masafumi / Ito, Tetsuhide / Nakamori, Shoji / Ishii, Hiroshi / Kodama, Yuzo / Morizane, Chigusa / Okusaka, Takuji / Yanagimoto, Hiroaki / Notohara, Kenji / Taguchi, Hiroki / Kitano, Masayuki / Yane, Kei / Maguchi, Hiroyuki / Tsuchiya, Yoshiaki / Komoto, Izumi / Tanaka, Hiroki / Tsuji, Akihito / Hashigo, Syunpei / Kawaguchi, Yoshiaki / Mine, Tetsuya / Kanno, Atsushi / Murohisa, Go / Miyabe, Katsuyuki / Takagi, Tadayuki / Matayoshi, Nobutaka / Yoshida, Tsukasa / Hara, Kazuo / Imamura, Masayuki / Furuse, Junji / Yatabe, Yasushi / Mizuno, Nobumasa. ·Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. rizasusu@aichi-cc.jp. · Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan. · Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan. · Division of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, Yokohama, Japan. · Department of Hepato-Biliary-Pancreatology, National Kyushu Cancer Center, Fukuoka, Japan. · Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. · Department of Oncology, Yokohama City University Hospital, Yokohama, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. · Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Hepato-Biliary-Pancreatic Surgery, Osaka National Hospital, Osaka, Japan. · Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. · Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Department of Surgery, Kansai Medical University, Hirakata, Japan. · Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan. · Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. · Department of Gastroenterology and Hepatology, Kinki University Faculty of Medicine, Sayama, Japan. · Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan. · Department of Surgery, Niigata Cancer Center Hospital, Niigata, Japan. · Department of Surgery, Kansai Electric Power Hospital, Osaka, Japan. · Department of Gastroenterology, Suzuka General Hospital, Suzuka, Japan. · Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan. · Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. · Department of Gastroenterology, Tokai University School of Medicine, Isehara, Japan. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. · Department of Gastroenterology, Seirei Hamamatsu General Hospital, Hamamatsu, Japan. · Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. · Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan. · Department of Surgery I, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Department of Neuroendocrine Tumor Center, Kansai Electric Power Hospital, Osaka, Japan. · Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan. ·Clin Cancer Res · Pubmed #28455360.

ABSTRACT:

8 Article Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk. 2016

Campa, Daniele / Pastore, Manuela / Gentiluomo, Manuel / Talar-Wojnarowska, Renata / Kupcinskas, Juozas / Malecka-Panas, Ewa / Neoptolemos, John P / Niesen, Willem / Vodicka, Pavel / Delle Fave, Gianfranco / Bueno-de-Mesquita, H Bas / Gazouli, Maria / Pacetti, Paola / Di Leo, Milena / Ito, Hidemi / Klüter, Harald / Soucek, Pavel / Corbo, Vincenzo / Yamao, Kenji / Hosono, Satoyo / Kaaks, Rudolf / Vashist, Yogesh / Gioffreda, Domenica / Strobel, Oliver / Shimizu, Yasuhiro / Dijk, Frederike / Andriulli, Angelo / Ivanauskas, Audrius / Bugert, Peter / Tavano, Francesca / Vodickova, Ludmila / Zambon, Carlo Federico / Lovecek, Martin / Landi, Stefano / Key, Timothy J / Boggi, Ugo / Pezzilli, Raffaele / Jamroziak, Krzysztof / Mohelnikova-Duchonova, Beatrice / Mambrini, Andrea / Bambi, Franco / Busch, Olivier / Pazienza, Valerio / Valente, Roberto / Theodoropoulos, George E / Hackert, Thilo / Capurso, Gabriele / Cavestro, Giulia Martina / Pasquali, Claudio / Basso, Daniela / Sperti, Cosimo / Matsuo, Keitaro / Büchler, Markus / Khaw, Kay-Tee / Izbicki, Jakob / Costello, Eithne / Katzke, Verena / Michalski, Christoph / Stepien, Anna / Rizzato, Cosmeri / Canzian, Federico. ·Department of Biology, University of Pisa, Pisa, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Institute of Experimental Medicine, Czech Academy of Science, Prague, Czech Republic. · Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic. · Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University of Rome, Rome, Italy. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. · Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. · Oncological Department Massa Carrara Azienda USL Toscana Nord Ovest, Carrara, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Division Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan. · Institute of Transfusion Medicine and Immunology, German Red Cross Blood Service Baden-Württemberg - Hessen gGmbH, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. · Laboratory of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic. · Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic. · ARC-Net Research Centre, and Department of Diagnostics and Public Health University and Hospital Trust of Verona, Verona, Italy. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan. · Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands. · Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Prague, Czech Republic. · Department of Medicine - DIMED, University of Padova, Padova, Italy. · Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. · Epidemiology Unit Nuffield Department of Population Health University of Oxford, Oxford, UK. · Division of General and Transplant Surgery, Pisa University Hospital, Pisa, Italy. · Pancreas Unit, Department of Digestive System, Dant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland. · Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. · Blood Transfusion Service, Azienda Ospedaliero Universitaria Meyer, Florence, Italy. · Department of Surgery, Academic Medical Centre, Amsterdam, The Netherlands. · Colorectal Unit, First Department of Propaedeutic Surgery, Athens Medical School, National and Kapodistrian University of Athens, Athens, Greece. · Department of Surgery, Oncology and Gastroenterology-DiSCOG, University of Padova, Padova, Italy. · Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy. · Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan. · Clinical Gerontology Unit, Addenbrooke’s Hospital, School of Clinical Medicine, University of Cambridge, Cambridge, UK. · Laboratory of Clinical, Transplant Immunology and Genetics, Copernicus Memorial Hospital, Lodz, Poland. · Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. ·Oncotarget · Pubmed #27486979.

ABSTRACT: The CDKN2A (p16) gene plays a key role in pancreatic cancer etiology. It is one of the most commonly somatically mutated genes in pancreatic cancer, rare germline mutations have been found to be associated with increased risk of developing familiar pancreatic cancer and CDKN2A promoter hyper-methylation has been suggested to play a critical role both in pancreatic cancer onset and prognosis. In addition several unrelated SNPs in the 9p21.3 region, that includes the CDNK2A, CDNK2B and the CDNK2B-AS1 genes, are associated with the development of cancer in various organs. However, association between the common genetic variability in this region and pancreatic cancer risk is not clearly understood. We sought to fill this gap in a case-control study genotyping 13 single nucleotide polymorphisms (SNPs) in 2,857 pancreatic ductal adenocarcinoma (PDAC) patients and 6,111 controls in the context of the Pancreatic Disease Research (PANDoRA) consortium. We found that the A allele of the rs3217992 SNP was associated with an increased pancreatic cancer risk (ORhet=1.14, 95% CI 1.01-1.27, p=0.026, ORhom=1.30, 95% CI 1.12-1.51, p=0.00049). This pleiotropic variant is reported to be a mir-SNP that, by changing the binding site of one or more miRNAs, could influence the normal cell cycle progression and in turn increase PDAC risk. In conclusion, we observed a novel association in a pleiotropic region that has been found to be of key relevance in the susceptibility to various types of cancer and diabetes suggesting that the CDKN2A/B locus could represent a genetic link between diabetes and pancreatic cancer risk.

9 Article Associations between polymorphisms in folate-metabolizing genes and pancreatic cancer risk in Japanese subjects. 2016

Nakao, Haruhisa / Wakai, Kenji / Ishii, Norimitsu / Kobayashi, Yuji / Ito, Kiyoaki / Yoneda, Masashi / Mori, Mitsuru / Nojima, Masanori / Kimura, Yasutoshi / Endo, Takao / Matsuyama, Masato / Ishii, Hiroshi / Ueno, Makoto / Kuruma, Sawako / Egawa, Naoto / Matsuo, Keitaro / Hosono, Satoyo / Ohkawa, Shinichi / Nakamura, Kozue / Tamakoshi, Akiko / Takahashi, Mami / Shimada, Kazuaki / Nishiyama, Takeshi / Kikuchi, Shogo / Lin, Yingsong. ·Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan. · Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan. · Department of Public Health, Sapporo Medical University School of Medicine, Sapporo, 060-0061, Japan. · Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, 060-8543, Japan. · Sapporo Shirakaba-dai Hospital, Sapporo, 062-0052, Japan. · Hepatobiliary and Pancreatic Section, Gastroenterological Division, Cancer Institute Hospital, Tokyo, 135-8550, Japan. · Clinical Research Center, National Hospital Organization Shikoku Cancer Center, Matsuyama, 791-0280, Japan. · Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center Hospital, Kanagawa, 241-8515, Japan. · Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, 113-8677, Japan. · Tokyo Metropolitan Otsuka Hospital, Tokyo, 170-8476, Japan. · Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, 762-6111, Japan. · Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan. · Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, 762-6111, Japan. · Department of Food and Nutrition, Gifu City Women's College, Gifu, 501-2592, Japan. · Department of Public Health, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan. · Central Animal Division, National Cancer Center Research Institute, Tokyo, 104-0045, Japan. · Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, 104-0045, Japan. · Department of Public Health, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan. · Department of Public Health, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan. linys@aichi-med-u.ac.jp. ·BMC Gastroenterol · Pubmed #27473058.

ABSTRACT: BACKGROUND: Evidence supporting the associations between folate metabolizing gene polymorphisms and pancreatic cancer has been inconclusive. We examined their associations in a case-control study of Japanese subjects. METHODS: Our case-control study involved 360 newly diagnosed pancreatic cancer cases and 400 frequency-matched, non-cancer control subjects. We genotyped four folate metabolizing gene polymorphisms, including two polymorphisms (rs1801133 and rs1801131) in the methylenetetrahydrofolate (MTHFR) gene, one polymorphism (rs1801394) in the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene and one polymorphism (rs1805087) in the 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) gene. Genotyping was performed using Fluidigm SNPtype assays. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the associations between folate metabolizing gene variants and pancreatic cancer risk. RESULTS: Overall we did not observe a significant association between these four genotypes and pancreatic cancer risk. For rs1801133, compared with individuals with the CC genotype of MTHFR C677T, the OR for those with the CT genotype and TT genotype was 0.87 (0.62-1.22) and 0.99 (0.65-1.51), respectively. For rs1801131, individuals with the CC genotype had approximately 1.2-fold increased risk compared with those with the AA genotype, but the association was not statistically significant. In analyses stratified by smoking and drinking status, no significant associations were noted for C677T genotypes. No significant interactions were observed with smoking and drinking with respect to pancreatic cancer risk. CONCLUSIONS: Our data did not support the hypothesis that MTHFR polymorphisms or other polymorphisms in the folate metabolizing pathway are associated with pancreatic cancer risk.

10 Article Genome-wide association study-identified SNPs (rs3790844, rs3790843) in the NR5A2 gene and risk of pancreatic cancer in Japanese. 2015

Ueno, Makoto / Ohkawa, Shinichi / Morimoto, Manabu / Ishii, Hiroshi / Matsuyama, Masato / Kuruma, Sawako / Egawa, Naoto / Nakao, Haruhisa / Mori, Mitsuru / Matsuo, Keitaro / Hosono, Satoyo / Nojima, Masanori / Wakai, Kenji / Nakamura, Kozue / Tamakoshi, Akiko / Takahashi, Mami / Shimada, Kazuaki / Nishiyama, Takeshi / Kikuchi, Shogo / Lin, Yingsong. ·Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center Hospital, Kanagawa 241-8515, Japan. · Hepatobiliary and Pancreatic Section, Gastroenterological Division, Cancer Institute Hospital, Tokyo 135-8550, Japan. · Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo 113-8677, Japan. · Tokyo Metropolitan Ohtsuka Hospital, Tokyo 170-8476, Japan. · Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1195, Japan. · Department of Public Health, Sapporo Medical University School of Medicine, Sapporo 060-0061, Japan. · Division of Molecular Medicine, Aichi Cancer Center Research Insitute, Nagoya 762-6111, Japan. · Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. · Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya 762-6111, Japan. · Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. · Department of Food and Nutrition, Gifu City Women's College, Gifu 501-2592, Japan. · Department of Public Health, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. · Central Animal Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan. · Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo 104-0045, Japan. · Department of Public Health, Aichi Medical University School of Medicine, Nagakute 480-1195, Japan. ·Sci Rep · Pubmed #26592175.

ABSTRACT: We genotyped 2 SNPs (rs3790844 T/C and rs3790843 G/A) in the NR5A2 gene that were identified in a genome-wide association study (GWAS) of pancreatic cancer in populations of mainly European ancestry, and we examined their associations with pancreatic cancer risk in a case-control study of 360 patients and 400 control subjects in Japan. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The SNPs were in linkage disequilibrium (r(2) = 0.80). For rs3790843, the multivariable-adjusted OR was 0.75 (95% CI: 0.41-1.36) and 0.60 (95%CI: 0.33-1.08) for subjects with the AG and AA genotype, respectively, compared to subjects with the GG genotype. The per allele OR was 0.78 (0.62-0.99) (P = 0.046). For rs3790844, the multivariable-adjusted OR was 0.65 (95% CI: 0.37-1.14) and 0.47 (95%CI: 0.27-0.83) for subjects with the CT and CC genotype, respectively, compared to subjects with the TT genotype. The per allele OR was 0.70 (0.56-0.89) (P = 0.003). Our case-control study found that rs3790843 and rs3790844 in the NR5A2 gene are associated with pancreatic cancer risk in Japanese subjects. The direction of association is consistent with the prior findings from GWASs.

11 Article Case-control study of diabetes-related genetic variants and pancreatic cancer risk in Japan. 2014

Kuruma, Sawako / Egawa, Naoto / Kurata, Masanao / Honda, Goro / Kamisawa, Terumi / Ueda, Junko / Ishii, Hiroshi / Ueno, Makoto / Nakao, Haruhisa / Mori, Mitsuru / Matsuo, Keitaro / Hosono, Satoyo / Ohkawa, Shinichi / Wakai, Kenji / Nakamura, Kozue / Tamakoshi, Akiko / Nojima, Masanori / Takahashi, Mami / Shimada, Kazuaki / Nishiyama, Takeshi / Kikuchi, Shogo / Lin, Yingsong. ·Sawako Kuruma, Terumi Kamisawa, Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo 113-8677, Japan. ·World J Gastroenterol · Pubmed #25516658.

ABSTRACT: AIM: To examine whether diabetes-related genetic variants are associated with pancreatic cancer risk. METHODS: We genotyped 7 single-nucleotide polymorphisms (SNPs) in PPARG2 (rs1801282), ADIPOQ (rs1501299), ADRB3 (rs4994), KCNQ1 (rs2237895), KCNJ11 (rs5219), TCF7L2 (rs7903146), and CDKAL1 (rs2206734), and examined their associations with pancreatic cancer risk in a multi-institute case-control study including 360 cases and 400 controls in Japan. A self-administered questionnaire was used to collect detailed information on lifestyle factors. Genotyping was performed using Fluidigm SNPtype assays. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between these diabetes-associated variants and pancreatic cancer risk. RESULTS: With the exception of rs1501299 in the ADIPOQ gene (P = 0.09), no apparent differences in genotype frequencies were observed between cases and controls. Rs1501299 in the ADPIOQ gene was positively associated with pancreatic cancer risk; compared with individuals with the AA genotype, the age- and sex-adjusted OR was 1.79 (95%CI: 0.98-3.25) among those with the AC genotype and 1.86 (95%CI: 1.03-3.38) among those with the CC genotype. The ORs remained similar after additional adjustment for body mass index and cigarette smoking. In contrast, rs2237895 in the KCNQ1 gene was inversely related to pancreatic cancer risk, with a multivariable-adjusted OR of 0.62 (0.37-1.04) among individuals with the CC genotype compared with the AA genotype. No significant associations were noted for other 5 SNPs. CONCLUSION: Our case-control study indicates that rs1501299 in the ADIPOQ gene may be associated with pancreatic cancer risk. These findings should be replicated in additional studies.

12 Article Lack of associations between genetic polymorphisms in GSTM1, GSTT1 and GSTP1 and pancreatic cancer risk: a multi-institutional case-control study in Japan. 2014

Yamada, Ikuhiro / Matsuyama, Masato / Ozaka, Masato / Inoue, Dai / Muramatsu, Yusuke / Ishii, Hiroshi / Junko, Ueda / Ueno, Makoto / Egawa, Naoto / Nakao, Haruhisa / Mori, Mitsuru / Matsuo, Keitaro / Nishiyama, Takeshi / Ohkawa, Shinichi / Hosono, Satoyo / Wakai, Kenji / Nakamura, Kozue / Tamakoshi, Akiko / Kuruma, Sawako / Nojima, Masanori / Takahashi, Mami / Shimada, Kazuaki / Yagyu, Kiyoko / Kikuchi, Shogo / Lin, Yingsong. ·Hepatobiliary and Pancreatic Section, Gastroenterological Division, Cancer Institute Hospital, Tokyo, Japan E-mail : linys@aichi-med-u.ac.jp. ·Asian Pac J Cancer Prev · Pubmed #24528063.

ABSTRACT: BACKGROUND: We aimed to evaluate the role of genetic polymorphisms in tobacco carcinogen-metabolizing genes and their interactions with smoking in a hospital-based case-control study of Japanese subjects. MATERIALS AND METHODS: We examine the associations of pancreatic cancer risk with genetic polymorphisms in GSTM1, GSTT1 and GSTP1, phase II enzymes that catalyze the conjugation of toxic and carcinogenic electrophilic molecules. The study population consisted of 360 patients and 400 control subjects, who were recruited from several medical facilities in Japan. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between genotypes and pancreatic cancer risk. RESULTS: Among the control subjects, the prevalence of the GSTM1-null genotype and the GSTT1-null genotype was approximately 56% and 48%, respectively. Cases and controls were comparable in terms of GSTM1 and GSTT1 genotype distributions. Neither of the deleted polymorphisms in GSTM1 and GSTT1 was associated with the risk of pancreatic cancer, with an age- and sex-adjusted OR of 0.99 (95%CI: 0.74-1.32) for the GSTM1-null genotype, and 0.98 (95%CI: 0.73-1.31) for the GSTT1-null genotype. The OR was 0.97 (95%CI: 0.64-1.47) for individuals with the GSTM1 and GSTT1-null genotypes compared with those with the GSTM1 and GSTT1- present genotypes. No synergistic effects of smoking or GST genotypes were observed. CONCLUSIONS: Our results indicate no overall association between the GSTM1 and GSTT1 deletion polymorphisms and pancreatic cancer risk in the Japanese subjects in our study.

13 Article Cigarette smoking and pancreatic cancer risk: a revisit with an assessment of the nicotine dependence phenotype. 2013

Nakao, Makoto / Hosono, Satoyo / Ito, Hidemi / Oze, Isao / Watanabe, Miki / Mizuno, Nobumasa / Yatabe, Yasushi / Yamao, Kenji / Niimi, Akio / Tajima, Kazuo / Tanaka, Hideo / Matsuo, Keitaro. ·Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan. kmatsuo@aichi-cc.jp ·Asian Pac J Cancer Prev · Pubmed #23992012.

ABSTRACT: BACKGROUND: Cigarette smoking is a well-established risk factor of pancreatic cancer (PC). Although an association between nicotine dependence phenotype, namely time to first cigarette (TTFC) after waking, and the risk of several smoking-related cancers has been reported, an association between TTFC and PC risk has not been reported. We assessed the impact of smoking behavior, particularly TTFC, on PC risk in a Japanese population. MATERIALS AND METHODS: We conducted a case-control study using 341 PC and 1,705 non-cancer patients who visited Aichi Cancer Center in Nagoya, Japan. Exposure to risk factors, including smoking behavior, was assessed from the results of a self-administered questionnaire. The impact of smoking on PC risk was assessed with multivariate logistic regression analysis adjusted for potential confounders to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Cigarettes per day (CPD) and/or smoking duration were significantly associated with PC risk, consistent with previous studies. For TTFC and PC risk, we found only a suggestive association: compared with a TTFC of more than 60 minutes, ORs were 1.15 (95%CI, 0.65- 2.04) for a TTFC of 30-60 minutes and 1.35 (95%CI, 0.85-2.15) for that of 0-30 minutes (p trend=0.139). After adjustment for CPD or smoking duration, no association was observed between TTFC and PC. CONCLUSIONS: In this study, we found no statistically significant association between TTFC and PC risk. Further studies concerning TTFC and PC risk are warranted.

14 Article Association between variations in the fat mass and obesity-associated gene and pancreatic cancer risk: a case-control study in Japan. 2013

Lin, Yingsong / Ueda, Junko / Yagyu, Kiyoko / Ishii, Hiroshi / Ueno, Makoto / Egawa, Naoto / Nakao, Haruhisa / Mori, Mitsuru / Matsuo, Keitaro / Kikuchi, Shogo. ·Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan. ·BMC Cancer · Pubmed #23835106.

ABSTRACT: BACKGROUND: It is clear that genetic variations in the fat mass and obesity-associated (FTO) gene affect body mass index and the risk of obesity. Given the mounting evidence showing a positive association between obesity and pancreatic cancer, this study aimed to investigate the relation between variants in the FTO gene, obesity and pancreatic cancer risk. METHODS: We conducted a hospital-based case-control study in Japan to investigate whether genetic variations in the FTO gene were associated with pancreatic cancer risk. We genotyped rs9939609 in the FTO gene of 360 cases and 400 control subjects. An unconditional logistic model was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between rs9939609 and pancreatic cancer risk. RESULTS: The minor allele frequency of rs9939609 was 0.18 among control subjects. BMI was not associated with pancreatic cancer risk. Compared with individuals with the common homozygous TT genotype, those with the heterozygous TA genotype and the minor homozygous AA genotype had a 48% (OR=1.48; 95%CI: 1.07-2.04), and 66% increased risk (OR=1.66; 95%CI: 0.70-3.90), respectively, of pancreatic cancer after adjustment for sex, age, body mass index, cigarette smoking and history of diabetes. The per-allele OR was 1.41 (95%CI: 1.07-1.85). There were no significant interactions between TA/AA genotypes and body mass index. CONCLUSIONS: Our findings indicate that rs9939609 in the FTO gene is associated with pancreatic cancer risk in Japanese subjects, possibly through a mechanism that is independent of obesity. Further investigation and replication of our results is required in other independent samples.

15 Article Association of body mass index and risk of death from pancreas cancer in Asians: findings from the Asia Cohort Consortium. 2013

Lin, Yingsong / Fu, Rong / Grant, Eric / Chen, Yu / Lee, Jung Eun / Gupta, Prakash C / Ramadas, Kunnambath / Inoue, Manami / Tsugane, Shoichiro / Gao, Yu-Tang / Tamakoshi, Akiko / Shu, Xiao-Ou / Ozasa, Kotaro / Tsuji, Ichiro / Kakizaki, Masako / Tanaka, Hideo / Chen, Chien-Jen / Yoo, Keun-Young / Ahn, Yoon-Ok / Ahsan, Habibul / Pednekar, Mangesh S / Sauvaget, Catherine / Sasazuki, Shizuka / Yang, Gong / Xiang, Yong-Bing / Ohishi, Waka / Watanabe, Takashi / Nishino, Yoshikazu / Matsuo, Keitaro / You, San-Lin / Park, Sue K / Kim, Dong-Hyun / Parvez, Faruque / Rolland, Betsy / McLerran, Dale / Sinha, Rashmi / Boffetta, Paolo / Zheng, Wei / Thornquist, Mark / Feng, Ziding / Kang, Daehee / Potter, John D. ·Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan. linys@aichi-med-u.ac.jp ·Eur J Cancer Prev · Pubmed #23044748.

ABSTRACT: We aimed to examine the association between BMI and the risk of death from pancreas cancer in a pooled analysis of data from the Asia Cohort Consortium. The data for this pooled analysis included 883 529 men and women from 16 cohort studies in Asian countries. Cox proportional-hazards models were used to estimate the hazard ratios and 95% confidence intervals for pancreas cancer mortality in relation to BMI. Seven predefined BMI categories (<18.5, 18.5-19.9, 20.0-22.4, 22.5-24.9, 25.0-27.4, 27.5-29.9, ≥ 30) were used in the analysis, with BMI of 22.5-24.9 serving as the reference group. The multivariable analyses were adjusted for known risk factors, including age, smoking, and a history of diabetes. We found no statistically significant overall association between each BMI category and the risk of death from pancreas cancer in all Asians, and obesity was unrelated to the risk of mortality in both East Asians and South Asians. Age, smoking, and a history of diabetes did not modify the association between BMI and the risk of death from pancreas cancer. In planned subgroup analyses among East Asians, an increased risk of death from pancreas cancer among those with a BMI less than 18.5 was observed for individuals with a history of diabetes; hazard ratio=2.01 (95% confidence interval: 1.01-4.00) (P for interaction=0.07). The data do not support an association between BMI and the risk of death from pancreas cancer in these Asian populations.

16 Article Selected polymorphisms of base excision repair genes and pancreatic cancer risk in Japanese. 2012

Nakao, Makoto / Hosono, Satoyo / Ito, Hidemi / Watanabe, Miki / Mizuno, Nobumasa / Sato, Shigeki / Yatabe, Yasushi / Yamao, Kenji / Ueda, Ryuzo / Tajima, Kazuo / Tanaka, Hideo / Matsuo, Keitaro. ·Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan. ·J Epidemiol · Pubmed #22850545.

ABSTRACT: BACKGROUND: Although several reports have described a possible association between DNA repair genes and pancreatic cancer (PC) in smokers, this association has not been fully evaluated in an Asian population. We assessed the impact of genetic polymorphisms in the base excision repair (BER) pathway on PC risk among Japanese. METHODS: This case-control study compared the frequency of 5 single-nucleotide polymorphisms (SNPs) of BER genes, namely rs1052133 in OGG1, rs1799782 and rs25487 in XRCC1, rs1130409 in APE1, and rs1136410 in PARP1. SNPs were investigated using the TaqMan assay in 185 PC cases and 1465 controls. Associations of PC risk with genetic polymorphisms and gene-environment interaction were examined with an unconditional logistic regression model. Exposure to risk factors was assessed from the results of a self-administered questionnaire. We also performed haplotype-based analysis. RESULTS: We observed that the minor allele of rs25487 in XRCC1 was significantly associated with PC risk in the per-allele model (odds ratio = 1.29, CI = 1.01-1.65; trend P = 0.043). Haplotype analysis of XRCC1 also showed a statistically significant association with PC risk. No statistically significant interaction between XRCC1 polymorphisms and smoking status was seen. CONCLUSIONS: Our findings suggest that XRCC1 polymorphisms affect PC risk in Japanese.

17 Article ABO blood group alleles and the risk of pancreatic cancer in a Japanese population. 2011

Nakao, Makoto / Matsuo, Keitaro / Hosono, Satoyo / Ogata, Saeko / Ito, Hidemi / Watanabe, Miki / Mizuno, Nobumasa / Iida, Shinsuke / Sato, Shigeki / Yatabe, Yasushi / Yamao, Kenji / Ueda, Ryuzo / Tajima, Kazuo / Tanaka, Hideo. ·Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan. ·Cancer Sci · Pubmed #21306478.

ABSTRACT: Several studies have investigated a possible association between the ABO blood group and the risk of pancreatic cancer (PC), but this association has not been fully evaluated in Asian populations. The present study aimed to assess the impact of genotype-derived ABO blood types, particularly ABO alleles, on the risk of PC in a Japanese population. We conducted a case-control study using 185 PC and 1465 control patients who visited Aichi Cancer Center in Nagoya, Japan. Using rs8176719 as a marker for the O allele, and rs8176746 and rs8176747 for the B allele, all participants' two ABO alleles were inferred. The impact of ABO blood type on PC risk was examined by multivariate analysis, with adjustment for potential confounders to estimate odds ratios (OR) and 95% confidence intervals (CI). An increased risk of PC was observed with the addition of any non-O allele (trend P = 0.012). Compared with subjects with the OO genotype, those with AO and BB genotypes had significantly increased OR of 1.67 (CI, 1.08-2.57) and 3.28 (CI, 1.38-7.80), respectively. Consistent with earlier reports showing a higher risk of PC for individuals with the non-O blood type, the previously reported protective allele (T) for rs505922 was found to be strongly correlated (r(2) = 0.96) with the O allele. In conclusion, this case-control study showed a statistically significant association between ABO blood group and PC risk in a Japanese population. Further studies are necessary to define the mechanisms by which the ABO gene or closely linked genetic variants influence PC risk.

18 Article Serum tumor antigen REG4 as a diagnostic biomarker in pancreatic ductal adenocarcinoma. 2010

Takayama, Reiko / Nakagawa, Hidewaki / Sawaki, Akira / Mizuno, Nobumasa / Kawai, Hiroki / Tajika, Masahiro / Yatabe, Yasushi / Matsuo, Keitaro / Uehara, Rie / Ono, Ken-ichiro / Nakamura, Yusuke / Yamao, Kenji. ·Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-0021, Japan. ·J Gastroenterol · Pubmed #19789838.

ABSTRACT: BACKGROUND AND AIMS: Serum biomarkers for the early detection of pancreatic cancer are not currently available. We evaluated the usefulness of a novel serum marker, REG4, in the diagnosis of pancreatic cancer, as compared to carbohydrate antigen (CA) 19-9. METHODS: We collected pretherapeutic sera from 92 patients with pancreatic cancer, as well as sera from 28 patients with other pancreatic tumors, 11 patients with pancreatitis, and 69 healthy controls. Serum levels of REG4 were measured using a standard sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with healthy controls, serum levels of REG4 were higher in pancreatic cancer patients (P < 0.001), and in patients with pancreatitis (P < 0.001). Receiver operating characteristic (ROC) analysis indicated that serum REG4 performed better than serum CA19-9 for distinguishing patients with pancreatic cancer from healthy controls [areas under the curve (AUC) for REG4 and CA19-9 were 0.922 and 0.884, respectively]. When we validated the study, the sensitivity of REG4 for pancreatic cancer was 94.9%, specificity was 64.0%, and accuracy was 77.5% for the REG4 cutoff value of 3.49 ng/ml. No correlation was seen between serum REG4 and CA19-9 levels, with the sensitivity, specificity, and accuracy of the combined markers reaching 100.0, 60.0, and 77.5%, respectively. No significant differences were seen among any stages of pancreatic cancer. In surgical specimens, immunohistochemical analysis found a correlation between serum REG4 levels and REG4 expression in pancreatic cancers. CONCLUSIONS: REG4 is expressed in pancreatic cancer, and serum levels of REG4 offer a useful indicator for distinguishing between patients with pancreatic cancer and healthy subjects. Serum REG4 has potential for use as a screening serum marker for pancreatic cancers, including early-stage cancers.