Two novel polymorphisms in 5' flanking region of the mesothelin gene are associated with soluble mesothelin-related peptide (SMRP) levels

Int J Biol Markers. Apr-Jun 2011;26(2):117-23. doi: 10.5301/JBM.2011.8332.

Abstract

Background and aims: 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.

MeSH terms

  • 5' Flanking Region / genetics
  • Asbestos / toxicity*
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics*
  • GPI-Linked Proteins / blood*
  • GPI-Linked Proteins / genetics*
  • Gene Frequency
  • Humans
  • Male
  • Mesothelioma / blood*
  • Mesothelioma / chemically induced
  • Middle Aged
  • Occupational Diseases / blood*
  • Occupational Diseases / chemically induced
  • Occupational Exposure*
  • Peptides / blood
  • Pleural Neoplasms / blood*
  • Pleural Neoplasms / chemically induced
  • Polymorphism, Genetic
  • Promoter Regions, Genetic

Substances

  • Biomarkers, Tumor
  • GPI-Linked Proteins
  • Peptides
  • Asbestos
  • mesothelin