Melanocortin-1 receptor, skin cancer and phenotypic characteristics (M-SKIP) project: study design and methods for pooling results of genetic epidemiological studies

BMC Medical Research Methodology

Tamar Nijsten^2,21  Manfred Kayser^1,14  Fan Liu^1,14  Francesco Sera²  Julia Newton-Bishop⁴  Julian Little^1,16  José C García-Borrón^3,34  Philippe Autier³  Terence H Wong⁹  Per Helsing¹  Sumiko Anno^1,10  Tomonori Motokawa^1,18  Lynn Cornelius^1,13  Alexander Stratigos⁵  Gloria Ribas^3,31  Giuseppe Palmieri^2,22  Maria Teresa Landi^2,29  Niels Morling^2,26  Tadeusz Debniak^2,25  Wojciech Branicki^1,19  Ricardo Fernandez-de-Misa^1,11  Leigh Blizzard^2,20  Terry Dwyer^2,27  Nelleke A Gruis^2,24  Paola Ghiorzo⁸  Peter A Kanetsky^2,23  Johan Hansson^1,15  Jiali Han^3,30  Eduardo Nagore^2,28  Rajiv Kumar⁶  Claudia Specchia^1,12  Patrick Maisonneuve^3,32  Vincenzo Bagnardi⁷  Maria Concetta Fargnoli^3,33  Sara Gandini^3,32  Sara Raimondi^1,17 

[1] Department of Dermatology, Oslo University Hospital, Oslo, Norway;UCL Institute of Child Health, London, UK;International Prevention Research Institute, Lyon, France;Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK;Department of Dermatology, University of Athens, Andreas Sygros Hospital, Athens, Greece;Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany;Department of Statistics, University of Milan Bicocca, Milan, Italy;Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy;Department of Dermatology, University of Edinburgh, Edinburgh, UK;Shibaura Institute of Technology, Tokyo, Japan;Servicio de Dermatologia, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain;Department of Biomedical Sciences and Biotechnologies, University of Brescia, Brescia, Italy;Division of Dermatology, Washington University, St. Louis, MO, USA;Department of Forensic Molecular Biology, Erasmus MC University Medical Center, Rotterdam, The Netherlands;Department of Oncology and Pathology, Cancer Center, Karolinska Institutet, Stockholm, Sweden;Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada;Department of Occupational Health, University of Milan, Milan, Italy;Dermatological R&D Skin Research Department, POLA Chemical Industries, Yokohama, Japan;Institute of Forensic Research, Krakow, Polandfv;Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia;Department of Dermatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands;Unit of Cancer Genetics, Istituto di Chimica Biomolecolare, CNR, Sassari, Italy;Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA;Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands;Department of Genetic and Pathology, Pomeranian Medical University, Polabska, Poland;Department of Forensic Medicine, University of Copenhagen, Copenhagen, Denmark;Murdoch Childrens Research Institute, Royal Children’s Hospital, Victoria, Australia;Department of Dermatology, Instituto Valenciano de Oncologia, Valencia, Spain;Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA;Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA;Dptd. Oncologia medica y hematologia, Fundacion Investigation Hospital Clinico Universitario de Valencia- INCLIVA, Valencia, Spain;Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ramusio 1, Milan, 20141, Italy;Department of Dermatology, University of L’Aquila, L’Aquila, Italy;Department of Biochemistry and Molecular Biology, University of Murcia, Murcia, Spain

关键词: Study design;    Skin cancer;    Pooled-analysis;    Meta-analysis;    Melanoma;    Genetic epidemiology;   

Others  :  1127039
DOI  :  10.1186/1471-2288-12-116

 received in 2012-04-19, accepted in 2012-07-23,  发布年份 2012

【 摘 要 】

Background

For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia.

Design and methods

Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer development will be studied via logic regression modeling.

Discussion

Methodological guidelines to correctly design and conduct pooled-analyses are needed to facilitate application of such methods, thus providing a better summary of the actual findings on specific fields.

【 授权许可】

   
2012 Raimondi et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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