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. 2012 Aug 3:12:116.
doi: 10.1186/1471-2288-12-116.

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

Sara Raimondi  1 , Sara Gandini, Maria Concetta Fargnoli, Vincenzo Bagnardi, Patrick Maisonneuve, Claudia Specchia, Rajiv Kumar, Eduardo Nagore, Jiali Han, Johan Hansson, Peter A Kanetsky, Paola Ghiorzo, Nelleke A Gruis, Terry Dwyer, Leigh Blizzard, Ricardo Fernandez-de-Misa, Wojciech Branicki, Tadeusz Debniak, Niels Morling, Maria Teresa Landi, Giuseppe Palmieri, Gloria Ribas, Alexander Stratigos, Lynn Cornelius, Tomonori Motokawa, Sumiko Anno, Per Helsing, Terence H Wong, Philippe Autier, José C García-Borrón, Julian Little, Julia Newton-Bishop, Francesco Sera, Fan Liu, Manfred Kayser, Tamar Nijsten; GEM Study Group; M-SKIP Study Group
Collaborators, Affiliations

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

Sara Raimondi et al. BMC Med Res Methodol. .

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.

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.

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Figures

Figure 1
Figure 1
Example of a logic tree representing the Boolean expression “more than 50 common naeviV [skin type IVΛ (MC1R R151CVbrown hair)]”.
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