title: Two novel polymorphisms in 5' flanking region of the mesothelin gene are associated with soluble mesothelin-related peptide (SMRP) levels.
abstract: OBJECTIVE
  Increased concentrations of soluble mesothelin-related peptides (SMRP) have been found in sera of patients with malignant pleural mesothelioma (MPM) even if a relatively high rate of false positives has hampered their clinical use as a tumor marker. Individual SMRP levels could be affected by polymorphic elements. The aim of this study was to investigate the association between single nucleotide polymorphisms within the promoter-5'UTR regions and SMRP levels in healthy asbestos-exposed individuals and patients suffering from MPM.?
  
  
  METHODS
  The promoter-5'UTR regions of the mesothelin gene were genotyped in 59 healthy asbestos-exposed subjects and 27 MPM patients. SMRP levels were measured using a commercially available ELISA kit.?
  
  
  RESULTS
  Two novel polymorphisms, an A>C variant (called New1) and a C>T variant (called New2), were identified. In healthy subjects, high SMRP levels were associated with the C-variant of New1, with an average 1.62-fold increase compared with AA homozygotes (p<0.0001). Most of the C-allele carriers had SMRP levels above the threshold of 1.00 nM. We set two different SMRP cutoffs on the basis of the combined New1+New2 genotypes.?
  
  
  CONCLUSIONS
  New1-New2 genotypes could be employed as markers for setting individualized and appropriate thresholds of "normality" when SMRP is used in surveillance programs of asbestos-exposed people.
authors.affiliation: Department of Endocrinology and Metabolism, Orthopedics and Traumatology, Occupational Medicine, University of Pisa - Italy. a.cristaudo@med.unipi.it
authors.forename: Alfonso
authors.initials: A
authors.lastname: Cristaudo
authors.forename: Rudy
authors.initials: R
authors.lastname: Foddis
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bonotti
authors.forename: Silvia
authors.initials: S
authors.lastname: Simonini
authors.forename: Agnese
authors.initials: A
authors.lastname: Vivaldi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Guglielmi
authors.forename: Rossella
authors.initials: R
authors.lastname: Bruno
authors.forename: Federica
authors.initials: F
authors.lastname: Gemignani
authors.forename: Stefano
authors.initials: S
authors.lastname: Landi
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D001194:Asbestos / Q000633:toxicity*; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D058851:GPI-Linked Proteins / Q000097:blood* / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D008297:Male; D000090204:Mesothelin; D008654:Mesothelioma / Q000097:blood* / Q000139:chemically induced; D008875:Middle Aged; D009784:Occupational Diseases / Q000097:blood* / Q000139:chemically induced; D016273:Occupational Exposure; D010455:Peptides / Q000097:blood; D010997:Pleural Neoplasms / Q000097:blood* / Q000139:chemically induced; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D010455:Peptides; D001194:Asbestos; D000090204:Mesothelin