title: A genome-wide association study for malignant mesothelioma risk.
abstract: Malignant mesothelioma (MM) is a uniformly fatal tumour of mesothelial cells. MM is caused by exposure to asbestos however most individuals with documented asbestos exposure do not develop MM. Although MM appears to aggregate within families, the genetics of MM susceptibility is a relatively unexplored area. The aim of the current study was to identify genetic factors that contribute to MM risk. A genome-wide association analysis of 2,508,203 single nucleotide polymorphisms (SNPs) from 428 MM cases and 1269 controls from Western Australia was performed. Additional genotyping was performed on a sample of 778 asbestos-exposed Western Australian controls. Replication of the most strongly associated SNPs was undertaken in an independent case-control study of 392 asbestos-exposed cases and 367 asbestos-exposed controls from Italy. No SNPs achieved formal genome-wide statistical significance in the Western Australian study. However, suggestive results for MM risk were identified in the SDK1, CRTAM and RASGRF2 genes, and in the 2p12 chromosomal region. These findings were not replicated in the Italian study, although there was some evidence of replication in the region of SDK1. These suggestive associations will be further investigated in sequencing and functional studies.
authors.affiliation: Centre for Genetic Origins of Health and Disease, University of Western Australia, 35 Stirling Hwy, Crawley, Western Australia 6009, Australia. Electronic address: gemma.cadby@uwa.edu.au.
authors.forename: Gemma
authors.initials: G
authors.lastname: Cadby
authors.forename: Sutapa
authors.initials: S
authors.lastname: Mukherjee
authors.forename: A W Bill
authors.initials: AW
authors.lastname: Musk
authors.forename: Alison
authors.initials: A
authors.lastname: Reid
authors.forename: Mike
authors.initials: M
authors.lastname: Garlepp
authors.forename: Ian
authors.initials: I
authors.lastname: Dick
authors.forename: Cleo
authors.initials: C
authors.lastname: Robinson
authors.forename: Jennie
authors.initials: J
authors.lastname: Hui
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fiorito
authors.forename: Simonetta
authors.initials: S
authors.lastname: Guarrera
authors.forename: John
authors.initials: J
authors.lastname: Beilby
authors.forename: Phillip E
authors.initials: PE
authors.lastname: Melton
authors.forename: Eric K
authors.initials: EK
authors.lastname: Moses
authors.forename: Donatella
authors.initials: D
authors.lastname: Ugolini
authors.forename: Dario
authors.initials: D
authors.lastname: Mirabelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonassi
authors.forename: Corrado
authors.initials: C
authors.lastname: Magnani
authors.forename: Irma
authors.initials: I
authors.lastname: Dianzani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matullo
authors.forename: Bruce
authors.initials: B
authors.lastname: Robinson
authors.forename: Jenette
authors.initials: J
authors.lastname: Creaney
authors.forename: Lyle J
authors.initials: LJ
authors.lastname: Palmer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008654:Mesothelioma / Q000235:genetics*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D020663:ras Guanine Nucleotide Exchange Factors / Q000235:genetics*
chemical_list: D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C504490:RASGRF2 protein, human; C493091:SDK1 protein, human; C408522:class-I restricted T cell-associated molecule; D020663:ras Guanine Nucleotide Exchange Factors
keywords: Asbestos; Case–control studies; Genetics; Genome-wide association study; Mesothelioma