Prostate stem-cell antigen gene is associated with diffuse and intestinal gastric cancer in Caucasians: Results from the EPIC-EURGAST study

Authors

  • Núria Sala,

    Corresponding author
    1. Molecular Epidemiology Group, Translational Research Laboratory, Catalan Institute of Oncology—IDIBELL, Barcelona, Spain
    2. Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology—IDIBELL, Barcelona, Spain
    • Translational Research Laboratory and Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology—IDIBELL, Gran Via de l'Hospitalet 199-203, 08907-Hospitalet de Llobregat, Barcelona, Spain
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    • Fax: +34-9-3260-7466.

    • *

      N.S. and X.M. contributed equally to this work

  • Xavier Muñoz,

    1. Molecular Epidemiology Group, Translational Research Laboratory, Catalan Institute of Oncology—IDIBELL, Barcelona, Spain
    2. Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology—IDIBELL, Barcelona, Spain
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  • Noemie Travier,

    1. Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology—IDIBELL, Barcelona, Spain
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  • Antonio Agudo,

    1. Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology—IDIBELL, Barcelona, Spain
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  • Eric J. Duell,

    1. Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology—IDIBELL, Barcelona, Spain
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  • Víctor Moreno,

    1. Biomarkers and Susceptibility Unit, Cancer Prevention and Control Program, Catalan Institute of Oncology—IDIBELL and University of Barcelona, Barcelona, Spain
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  • Kim Overvad,

    1. Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark
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  • Anne Tjonneland,

    1. Danish Cancer Society, Institute of Cancer Epidemiology, Diet Cancer and Health, Copenhagen, Denmark
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  • Marie Christine Boutron-Ruault,

    1. Centre for Research in Epidemiology and Population Health, Institut National de la Santé et de la Recherche Médicale (INSERM), ERI 20, EA 4045, Institut Gustave Roussy, Villejuif Cedex, France, Paris South University, Villejuif, France
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  • Françoise Clavel-Chapelon,

    1. Centre for Research in Epidemiology and Population Health, Institut National de la Santé et de la Recherche Médicale (INSERM), ERI 20, EA 4045, Institut Gustave Roussy, Villejuif Cedex, France, Paris South University, Villejuif, France
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  • Federico Canzian,

    1. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
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  • Rudolf Kaaks,

    1. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
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  • Heiner Boeing,

    1. Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke
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  • Karina Meidtner,

    1. Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke
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  • Antonia Trichopoulos,

    1. Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School, Athens, Greece and Hellenic Health Foundation, Athens, Greece
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  • Konstantine Tsiotas,

    1. Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School, Athens, Greece and Hellenic Health Foundation, Athens, Greece
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  • Dimosthenis Zylis,

    1. Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School, Athens, Greece and Hellenic Health Foundation, Athens, Greece
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  • Paolo Vineis,

    1. University of Turin, Turin, Italy
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  • Salvatore Panico,

    1. Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy
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  • Domenico Palli,

    1. Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy
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  • Vittorio Krogh,

    1. Department of Preventive and Predictive Medicine, Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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  • Rosario Tumino,

    1. Cancer Registry and Histopathology Unit, “Civile M.P. Arezzo” Hospital, Ragusa, Italy
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  • Eiliv Lund,

    1. Department of Community Medicine, University of Tromsø, Tromsø, Norway
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  • H. Bas Bueno-de-Mesquita,

    1. Centre of Chronic Diseases Epidemiology, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
    2. Department of Gastroenterology and Hepatology, University Medical Centre Utrecht (UMCU), Utrecht, The Netherlands
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  • Mattjis E. Numans,

    1. Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands
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  • Petra H.M. Peeters,

    1. Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands
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  • J. Ramon Quirós,

    1. Public Health and Health Planning Directorate, Asturias, Spain
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  • María-José Sánchez,

    1. Andalusian School of Public Health, Granada, Spain
    2. Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Murcia, Spain
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  • Camen Navarro,

    1. Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Murcia, Spain
    2. Department of Epidemiology, Murcia Health Council, Murcia, Spain
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  • Eva Ardanaz,

    1. Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Murcia, Spain
    2. Epidemiology of non-communicable diseases section, Navarre Public Health Institute, Pamplona, Spain
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  • Miren Dorronsoro,

    1. Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Murcia, Spain
    2. Public Health Division of Gipuzkoa, Basque Regional Health Department, Bilbao, Spain
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  • Göran Hallmans,

    1. Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden
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  • Roger Stenling,

    1. Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
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  • Jonas Manjer,

    1. Department of Surgery, Skåne University Hospital Malmö, Lund University, Malmö, Sweden
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  • Naomi E. Allen,

    1. Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
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  • Ruth C. Travis,

    1. Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
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  • Kay-Tee Khaw,

    1. Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
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  • Mazda Jenab,

    1. International Agency for Research on Cancer (IARC-WHO), Lyon, France
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  • G. Johan A. Offerhaus,

    1. Department of Pathology, University Medical Center, Utrecht, The Netherlands
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  • Elio Riboli,

    1. School of Public Health, Imperial College London, St Mary's Campus, Imperial College, London, United Kingdom
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  • Carlos A. González

    1. Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology—IDIBELL, Barcelona, Spain
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Abstract

A genome-wide study performed in a Japanese population identified a strong association between SNP rs2294008 (Met1Thr) in the Prostate Stem Cell Antigen gene (PSCA) and diffuse-type gastric cancer (GC). This association was validated in different Asian populations, and, very recently, a study has been published in Caucasians. In this study, we analyzed the association between PSCA variation and GC risk in Caucasians from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Six tagSNPs covering the PSCA gene region were genotyped in 411 incident gastric adenocarcinoma cases and 1530 matched controls from a nested case–control study in the EPIC cohort. Associations were analyzed by unconditional logistic regression, adjusting for age, sex and country. The T allele of rs2294008 in PSCA was found to be a highly significant risk factor for GC (per allele OR = 1.42, 95% CI: 1.23–1.66, p-value = 6.5 × 10−6), particularly of the noncardia-type (per allele OR = 1.47, 95% CI: 1.19–1.81, p-value = 3 × 10−4). At contrast with previous studies, no significant differences were observed between the diffuse (per allele OR = 1.54, 95% CI: 1.20–1.96, p-value = 5 × 10−4) and the intestinal (per allele OR = 1.52, 95% CI: 1.20–1.93, p-value = 5 × 10−4) GC histological subtypes. Although rs12155758 and rs9297976 were also found associated with GC, this association appeared to be due to linkage disequilibrium with rs2294008. Haplotype analysis did not provide additional information. These results confirm the association between variation in the promoter region of PSCA and GC risk in Caucasians and also indicate that the rs2294008 variant is a similar risk factor for both the diffuse and intestinal-types of GC.

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