Publications by authors named "Eve Corda"

7 Publications

  • Page 1 of 1

Familial melanoma: clinical factors associated with germline CDKN2A mutations according to the number of patients affected by melanoma in a family.

J Am Acad Dermatol 2012 Dec 26;67(6):1257-64. Epub 2012 Jul 26.

INSERM (Institut National de Santé et de Recherche Médicale), Genetic Variation and Human Diseases Unit (U946), Paris, France.

Background: Features associated with an increased frequency of cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations have been identified in families with 3 or more patients with cutaneous melanoma (CM). However, in families with 2 patients with CM, which represent the majority of familial melanoma, these factors have been rarely studied.

Objective: We investigated association of 3 clinical features with the presence of a CDKN2A mutation in a family by extent of CM family clustering (2 vs ≥3 patients with CM among first-degree relatives in a family).

Methods: We included 483 French families that comprised 387 families with 2 patients with CM (F2 families) and 96 families with 3 or more patients with CM (F3+ families). Three clinical factors were examined individually and in a joint analysis: median age at diagnosis younger than 50 years, and 1 or more patient in a family with multiple primary melanoma or with pancreatic cancer.

Results: The frequency of CDKN2A mutations was higher in F3+ families (32%) than in F2 families (13%). Although early age at melanoma diagnosis and occurrence of multiple primary melanoma in 1 or more patient were significantly associated with the risk of a CDKN2A mutation in F2 families, early age at melanoma diagnosis and occurrence of pancreatic cancer in a family were significantly associated with CDKN2A mutations in F3+ families.

Limitations: The study was not population based.

Conclusions: This study shows that factors associated with CDKN2A mutations differ by extent of CM family clustering. It indicates that, in France, families with 2 patients with CM are eligible for genetic testing especially when there is an early age at CM diagnosis and/or 1 or more patients with multiple primary melanoma.
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http://dx.doi.org/10.1016/j.jaad.2012.05.014DOI Listing
December 2012

The ANO3/MUC15 locus is associated with eczema in families ascertained through asthma.

J Allergy Clin Immunol 2012 Jun;129(6):1547-53.e3

Genetic Variation and Human Diseases Unit, INSERM, U946, Paris, France; Université Paris, France.

Background: A previous genome-wide linkage scan in 295 families of the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) reported strong evidence of linkage of 11p14 to eczema.

Objective: Our purpose was to conduct fine-scale mapping of the 11p14 region to identify the genetic variants associated with eczema.

Methods: Association analyses were first conducted in the family sample from the French EGEA by using 2 methods: the family-based association method and logistic regression. Replication of the EGEA findings was sought in French Canadian and United Kingdom family samples, which, similarly to EGEA samples, were ascertained through asthma. We also tested for association in 2 German samples ascertained through eczema.

Results: We found significant association of eczema with 11p14 genetic variants in the vicinity of the linkage peak in EGEA (P = 10(-4) for rs1050153 by using the family-based association method, which reached the multiple testing-corrected threshold of 10(-4); P = .003 with logistic regression). Pooled analysis of the 3 asthma-ascertained samples showed strong improvement in the evidence for association (P = 6 × 10(-6) for rs293974, P = 3 × 10(-5) for rs1050153, and P = 8 × 10(-5) for rs15783). No association was observed in the eczema-ascertained samples.

Conclusion: The significant single nucleotide polymorphisms are located within the overlapping anoctamin 3 (ANO3) and mucin 15 (MUC15) genes. Several lines of evidence suggest that MUC15 is a strong candidate for eczema. Further investigation is needed to confirm our findings and to better understand the role of the ANO3/MUC15 locus in eczema and its relationship with respect to asthma.
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http://dx.doi.org/10.1016/j.jaci.2012.04.010DOI Listing
June 2012

A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma.

Authors:
Corine Bertolotto Fabienne Lesueur Sandy Giuliano Thomas Strub Mahaut de Lichy Karine Bille Philippe Dessen Benoit d'Hayer Hamida Mohamdi Audrey Remenieras Eve Maubec Arnaud de la Fouchardière Vincent Molinié Pierre Vabres Stéphane Dalle Nicolas Poulalhon Tanguy Martin-Denavit Luc Thomas Pascale Andry-Benzaquen Nicolas Dupin Françoise Boitier Annick Rossi Jean-Luc Perrot Bruno Labeille Caroline Robert Bernard Escudier Olivier Caron Laurence Brugières Simon Saule Betty Gardie Sophie Gad Stéphane Richard Jérôme Couturier Bin Tean Teh Paola Ghiorzo Lorenza Pastorino Susana Puig Celia Badenas Hakan Olsson Christian Ingvar Etienne Rouleau Rosette Lidereau Philippe Bahadoran Philippe Vielh Eve Corda Hélène Blanché Diana Zelenika Pilar Galan François Aubin Bertrand Bachollet Céline Becuwe Pascaline Berthet Yves Jean Bignon Valérie Bonadona Jean-Louis Bonafe Marie-Noëlle Bonnet-Dupeyron Fréderic Cambazard Jacqueline Chevrant-Breton Isabelle Coupier Sophie Dalac Liliane Demange Michel d'Incan Catherine Dugast Laurence Faivre Lynda Vincent-Fétita Marion Gauthier-Villars Brigitte Gilbert Florent Grange Jean-Jacques Grob Philippe Humbert Nicolas Janin Pascal Joly Delphine Kerob Christine Lasset Dominique Leroux Julien Levang Jean-Marc Limacher Cristina Livideanu Michel Longy Alain Lortholary Dominique Stoppa-Lyonnet Sandrine Mansard Ludovic Mansuy Karine Marrou Christine Matéus Christine Maugard Nicolas Meyer Catherine Nogues Pierre Souteyrand Laurence Venat-Bouvet Hélène Zattara Valérie Chaudru Gilbert M Lenoir Mark Lathrop Irwin Davidson Marie-Françoise Avril Florence Demenais Robert Ballotti Brigitte Bressac-de Paillerets

Nature 2011 Oct 19;480(7375):94-8. Epub 2011 Oct 19.

1] INSERM, U895 (équipe 1), Equipe labélisée Ligue Contre le Cancer, C3M, 06204 Nice, France [2] Université of Nice Sophia-Antipolis, UFR Médecine, 06204 Nice, France [3] Centre Hospitalier Universitaire de Nice, Service de Dermatologie, 06204 Nice, France [4].

So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes; risk factors associated with RCC include smoking, obesity and hypertension. A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene; it also stimulates the transcription of hypoxia inducible factor (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes. We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (ΨKXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K-occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer.
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http://dx.doi.org/10.1038/nature10539DOI Listing
October 2011

Genome-wide association study identifies three new melanoma susceptibility loci.

Nat Genet 2011 Oct 9;43(11):1108-13. Epub 2011 Oct 9.

Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Leeds Cancer Research UK Centre, St James’s University Hospital, Leeds, UK.

We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 × 10(-9)), an SNP in MX2 (rs45430, P = 2.9 × 10(-9)) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 × 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 × 10(-7) under a fixed-effects model and P = 1.2 × 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
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http://dx.doi.org/10.1038/ng.959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251256PMC
October 2011

Genome-wide association study identifies three loci associated with melanoma risk.

Nat Genet 2009 Aug 5;41(8):920-5. Epub 2009 Jul 5.

Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds, UK.

We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317K tagging SNPs for 1,650 selected cases and 4,336 controls, with replication in an additional two cohorts (1,149 selected cases and 964 controls from GenoMEL, and a population-based case-control study in Leeds of 1,163 cases and 903 controls). The genome-wide screen identified five loci with genotyped or imputed SNPs reaching P < 5 x 10(-7). Three of these loci were replicated: 16q24 encompassing MC1R (combined P = 2.54 x 10(-27) for rs258322), 11q14-q21 encompassing TYR (P = 2.41 x 10(-14) for rs1393350) and 9p21 adjacent to MTAP and flanking CDKN2A (P = 4.03 x 10(-7) for rs7023329). MC1R and TYR are associated with pigmentation, freckling and cutaneous sun sensitivity, well-recognized melanoma risk factors. Common variants within the 9p21 locus have not previously been associated with melanoma. Despite wide variation in allele frequency, these genetic variants show notable homogeneity of effect across populations of European ancestry living at different latitudes and show independent association to disease risk.
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http://dx.doi.org/10.1038/ng.411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2741419PMC
August 2009

Effect of 17q21 variants and smoking exposure in early-onset asthma.

N Engl J Med 2008 Nov 15;359(19):1985-94. Epub 2008 Oct 15.

INSERM Unité 794, Paris, France.

Background: A genomewide association study has shown an association between variants at chromosome 17q21 and an increased risk of asthma. To elucidate the relationship between this locus and disease, we examined a large, family-based data set that included extensive phenotypic and environmental data from the Epidemiological Study on the Genetics and Environment of Asthma.

Methods: We tested 36 single-nucleotide polymorphisms (SNPs) in the 17q21 region in 1511 subjects from 372 families for an association with asthma. We also tested for genetic heterogeneity according to the age at the onset of asthma and exposure to environmental tobacco smoke in early life.

Results: Eleven SNPs were significantly associated with asthma (P<0.01), of which three (rs8069176, rs2305480, and rs4795400) were strongly associated (P<0.001). Ordered-subset regression analysis led us to select an onset at 4 years of age or younger to classify patients as having early-onset asthma. Association with early-onset asthma was highly significant (P<10(-5) for four SNPs), whereas no association was found with late-onset asthma. With respect to exposure to environmental tobacco smoke in early life, we observed a significant association with early-onset asthma only in exposed subjects (P<5x10(-5) for six SNPs). Under the best-fitting recessive model, homozygous status (GG) at the most strongly associated SNP (rs8069176) conferred an increase in risk by a factor of 2.9, as compared with other genotypes (AG and AA) in the group exposed to environmental tobacco smoke (P=2.8x10(-6); P=0.006 for the test for heterogeneity of the SNP effect on early-onset asthma between groups with tobacco exposure and those without such exposure).

Conclusions: This study shows that the increased risk of asthma conferred by 17q21 genetic variants is restricted to early-onset asthma and that the risk is further increased by early-life exposure to environmental tobacco smoke. These findings provide a greater understanding of the functional role of the 17q21 variants in the pathophysiology of asthma.
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http://dx.doi.org/10.1056/NEJMoa0806604DOI Listing
November 2008