title: Melanocortin-1 receptor, skin cancer and phenotypic characteristics (M-SKIP) project: study design and methods for pooling results of genetic epidemiological studies.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ramusio 1, Milan, 20141, Italy. sara.raimondi@ieo.it
authors.forename: Sara
authors.initials: S
authors.lastname: Raimondi
authors.forename: Sara
authors.initials: S
authors.lastname: Gandini
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Fargnoli
authors.forename: Vincenzo
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authors.lastname: Bagnardi
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authors.lastname: Maisonneuve
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authors.forename: Jiali
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authors.lastname: Han
authors.forename: Johan
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authors.lastname: Hansson
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authors.lastname: Kanetsky
authors.forename: Paola
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authors.lastname: Ghiorzo
authors.forename: Nelleke A
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authors.lastname: Gruis
authors.forename: Terry
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authors.lastname: Dwyer
authors.forename: Leigh
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authors.lastname: Blizzard
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fernandez-de-Misa
authors.forename: Wojciech
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authors.lastname: Branicki
authors.forename: Tadeusz
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authors.lastname: Debniak
authors.forename: Niels
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authors.lastname: Morling
authors.forename: Maria Teresa
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authors.lastname: Landi
authors.forename: Giuseppe
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authors.lastname: Palmieri
authors.forename: Gloria
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authors.lastname: Ribas
authors.forename: Alexander
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authors.lastname: Stratigos
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authors.lastname: Cornelius
authors.forename: Tomonori
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authors.lastname: Motokawa
authors.forename: Sumiko
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authors.lastname: Anno
authors.forename: Per
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authors.lastname: Helsing
authors.forename: Terence H
authors.initials: TH
authors.lastname: Wong
authors.forename: Philippe
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authors.lastname: Autier
authors.forename: José C
authors.initials: JC
authors.lastname: García-Borrón
authors.forename: Julian
authors.initials: J
authors.lastname: Little
authors.forename: Julia
authors.initials: J
authors.lastname: Newton-Bishop
authors.forename: Francesco
authors.initials: F
authors.lastname: Sera
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
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authors.lastname: Kayser
authors.forename: Tamar
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authors.lastname: Nijsten
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003625:Data Collection / Q000592:standards; D003627:Data Interpretation, Statistical; D015340:Epidemiologic Research Design; D005260:Female; D020022:Genetic Predisposition to Disease; D006760:Hospitalization; D006801:Humans; D016015:Logistic Models; D008297:Male; D015201:Meta-Analysis as Topic; D010641:Phenotype; D044102:Receptor, Melanocortin, Type 1; D012878:Skin Neoplasms / Q000235:genetics* / Q000503:physiopathology / Q000556:secondary; D012907:Smoking; D013472:Sunlight / Q000009:adverse effects*
chemical_list: D044102:Receptor, Melanocortin, Type 1