J. Han
http://repub.eur.nl/ppl/5108/
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http://repub.eur.nl/
RePub, Erasmus University RepositoryMC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: A pooled-analysis from the M-SKIP project
http://repub.eur.nl/pub/72933/
Fri, 20 Jun 2014 00:00:01 GMT<div>E. Pasquali</div><div>J.C. García-Borrón</div><div>M.C. Fargnoli</div><div>S. Gandini</div><div>P. Maisonneuve</div><div>V. Bagnardi</div><div>C. Specchia</div><div>F. Liu</div><div>M.H. Kayser</div><div>T.E.C. Nijsten</div><div>E. Nagore</div><div>R. Kumar</div><div>J. Hansson</div><div>P.A. Kanetsky</div><div>P. Ghiorzo</div><div>T. Debniak</div><div>W. Branicki</div><div>N.A. Gruis</div><div>J. Han</div><div>T. Dwyer</div><div>L. Blizzard</div><div>M.T. Landi</div><div>D. Palmieri</div><div>G. Ribas</div><div>A. Stratigos</div><div>M.L. Council</div><div>P.J.M. Autier</div><div>J. Little</div><div>J. Newton-Bishop</div><div>J.P. de Sera</div><div>S. Raimondi</div>
The MC1R gene is a key regulator of skin pigmentation. We aimed to evaluate the association between MC1R variants and the risk of sporadic cutaneous melanoma (CM) within the M-SKIP project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. Data included 5,160 cases and 12,119 controls from 17 studies. We calculated a summary odds ratio (SOR) for the association of each of the nine most studied MC1R variants and of variants combined with CM by using random-effects models. Stratified analysis by phenotypic characteristics were also performed. Melanoma risk increased with presence of any of the main MC1R variants: the SOR for each variant ranged from 1.47 (95%CI: 1.17-1.84) for V60L to 2.74 (1.53-4.89) for D84E. Carriers of any MC1R variant had a 66% higher risk of developing melanoma compared with wild-type subjects (SOR; 95%CI: 1.66; 1.41-1.96) and the risk attributable to MC1R variants was 28%. When taking into account phenotypic characteristics, we found that MC1R-associated melanoma risk increased only for darker-pigmented Caucasians: SOR (95%CI) was 3.14 (2.06-4.80) for subjects with no freckles, no red hair and skin Type III/IV. Our study documents the important role of all the main MC1R variants in sporadic CM and suggests that they have a direct effect on melanoma risk, independently on the phenotypic characteristics of carriers. This is of particular importance for assessing preventive strategies, which may be directed to darker-pigmented Caucasians with MC1R variants as well as to lightly pigmented, fair-skinned subjects.Melanocortin-1 receptor, skin cancer and phenotypic characteristics (M-SKIP) project: Study design and methods for pooling results of genetic epidemiological studies
http://repub.eur.nl/pub/69511/
Tue, 07 Aug 2012 00:00:01 GMT<div>S. Raimondi</div><div>S. Gandini</div><div>M.C. Fargnoli</div><div>V. Bagnardi</div><div>P. Maisonneuve</div><div>C. Specchia</div><div>R. Kumar</div><div>E. Nagore</div><div>J. Han</div><div>J. Hansson</div><div>P.A. Kanetsky</div><div>P. Ghiorzo</div><div>N.A. Gruis</div><div>T. Dwyer</div><div>L. Blizzard</div><div>R. Fernandez-De-Misa</div><div>W. Branicki</div><div>T. Debniak</div><div>N. Morling</div><div>M.T. Landi</div><div>D. Palmieri</div><div>G. Ribas</div><div>A. Stratigos</div><div>L. Cornelius</div><div>T. Motokawa</div><div>H. Anno</div><div>P. Helsing</div><div>T.H. Wong</div><div>P.J.M. Autier</div><div>J.C. García-Borrón</div><div>J. Little</div><div>J. Newton-Bishop</div><div>J.P. de Sera</div><div>F. Liu</div><div>M.H. Kayser</div><div>T.E.C. Nijsten</div>
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.An entropic regularization approach for mathematical programs with equilibrium constraints
http://repub.eur.nl/pub/62138/
Mon, 01 Nov 2004 00:00:01 GMT<div>S.I. Birbil</div><div>S-C. Fang</div><div>J. Han</div>
A new smoothing approach based on entropic regularization is proposed for solving a mathematical program with equilibrium constraints (MPEC). With some known smoothing properties of the entropy function and keeping real practice in mind, we reformulate an MPEC problem as a smooth nonlinear programming problem. In this way, a difficult MPEC problem becomes solvable by using available nonlinear optimization software. To support our claims, we use an online solver and test the performance of the proposed approach on a set of well-known test problems.Entropic regularization approach for mathematical programs with equilibrium constraints
http://repub.eur.nl/pub/525/
Tue, 31 Dec 2002 00:00:01 GMT<div>S.I. Birbil</div><div>S.-C. Fang</div><div>J. Han</div>
A new smoothing approach based on entropic perturbation is proposed for solving mathematical
programs with equilibrium constraints. Some of the desirable properties of the smoothing
function are shown. The viability of the proposed approach is supported by a computational
study on a set of well-known test problems.On the finite termination of an entropy function based smoothing Newton method for vertical linear complementarity problems
http://repub.eur.nl/pub/527/
Tue, 31 Dec 2002 00:00:01 GMT<div>S.-C. Fang</div><div>J. Han</div><div>Z. Huang</div><div>S.I. Birbil</div>
By using a smooth entropy function to approximate the non-smooth max-type function, a
vertical linear complementarity problem (VLCP) can be treated as a family of parameterized
smooth equations. A Newton-type method with a testing procedure is proposed to solve such
a system. We show that the proposed algorithm finds an exact solution of VLCP in a finite
number of iterations, under some conditions milder than those assumed in literature.
Some computational results are included to illustrate the potential of this approach.On the Finite Termination of An Entropy Function Based Smoothing Newton Method for Vertical Linear Complementarity Problems
http://repub.eur.nl/pub/225/
Mon, 16 Sep 2002 00:00:01 GMT<div>S.I. Birbil</div><div>S-C. Fang</div><div>J. Han</div>
By using a smooth entropy function to approximate the non-smooth max-type function, a vertical
linear complementarity problem (VLCP) can be treated as a family of parameterized smooth
equations. A Newton-type method with a testing procedure is proposed to solve such
a system. We show that the proposed algorithm finds an exact solution of VLCP in a finite
number of iterations, under some conditions milder than those assumed in literature. Some
computational results are included to illustrate the potential of this approach.Entropic Regularization Approach for Mathematical Programs with Equilibrium Constraints
http://repub.eur.nl/pub/224/
Fri, 13 Sep 2002 00:00:01 GMT<div>S.I. Birbil</div><div>S-C. Fang</div><div>J. Han</div>
A new smoothing approach based on entropic perturbation
is proposed for solving mathematical programs with
equilibrium constraints. Some of the desirable
properties of the smoothing function are shown. The
viability of the proposed approach is supported by a
computationalstudy on a set of well-known test problems.