title: Iron signature in asbestos-induced malignant pleural mesothelioma: A population-based autopsy study.
abstract: Malignant pleural mesothelioma (MPM) is an aggressive cancer with poor prognosis. The development of MPM is frequently linked to inhalation of asbestos fibers. A genetic component of susceptibility to this disease is suggested by the observation that some individuals develop MPM following lower doses of asbestos exposure, whereas others exposed to higher quantities do not seem to be affected. This hypothesis is supported also by frequent reports of MPM familial clustering. Despite the widely recognized role of iron (Fe) in cellular asbestos-induced pulmonary toxicity, the role of the related gene polymorphisms in the etiology of MPM has apparently not been evaluated. Eighty-six single-nucleotide polymorphisms (SNPs) of 10 Fe-metabolism genes were examined by exploiting formalin-fixed paraffin-embedded postmortem samples from 77 patients who died due to MPM (designated AEM) and compared with 48 who were exposed to asbestos but from died in old age of cause other than asbestos (designated AENM). All subjects showed objective signs of asbestos exposure. Three SNPs, localized in the ferritin heavy polypeptide, transferrin, and hephaestin genes, whose frequencies were distributed differently in AEM and AENM populations, were identified. For ferritin and transferrin the C/C and the G/G genotypes, respectively, representing intronic polymorphisms, were significantly associated with protection against MPM and need to be considered as possible genetic markers of protection. Similarly, the C/C hephaestin SNP, a missense variation of this multicopper ferroxidase encoding gene, may be related, also functionally, with protection against MPM. In conclusion, it is proposed that three Fe metabolism-associated genes, significantly associated with protection against development of MPM, may serve as protective markers for this aggressive tumor.
authors.affiliation: a Institute for Maternal and Child Health, IRCCS Burlo Garofolo , Trieste , Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
authors.affiliation: a Institute for Maternal and Child Health, IRCCS Burlo Garofolo , Trieste , Italy.
authors.forename: Anna Monica
authors.initials: AM
authors.lastname: Bianco
authors.affiliation: a Institute for Maternal and Child Health, IRCCS Burlo Garofolo , Trieste , Italy.
authors.forename: Joseph
authors.initials: J
authors.lastname: Vuch
authors.affiliation: a Institute for Maternal and Child Health, IRCCS Burlo Garofolo , Trieste , Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Zupin
authors.affiliation: a Institute for Maternal and Child Health, IRCCS Burlo Garofolo , Trieste , Italy.
authors.forename: Ronald Rodrigues
authors.initials: RR
authors.lastname: Moura
authors.affiliation: b Department of Life Science , University of Trieste , Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Trevisan
authors.affiliation: c Laboratory of Pathological Anatomy , Hospital of Monfalcone (GO), Ass2 , Gorizia , Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Schneider
authors.affiliation: c Laboratory of Pathological Anatomy , Hospital of Monfalcone (GO), Ass2 , Gorizia , Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Brollo
authors.affiliation: c Laboratory of Pathological Anatomy , Hospital of Monfalcone (GO), Ass2 , Gorizia , Italy.
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Nicastro
authors.affiliation: d Department of Medicine , Hospital of Monfalcone (GO), Ass2 , Gorizia , Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cosenzi
authors.affiliation: b Department of Life Science , University of Trieste , Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Zabucchi
authors.affiliation: b Department of Life Science , University of Trieste , Italy.
authors.forename: Violetta
authors.initials: V
authors.lastname: Borelli
mesh_terms: D000328:Adult; D000368:Aged; D001194:Asbestos / Q000633:toxicity*; D001344:Autopsy; D016022:Case-Control Studies; D005260:Female; D005293:Ferritins / Q000235:genetics; D005787:Gene Frequency; D005819:Genetic Markers; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008654:Mesothelioma / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D020125:Mutation, Missense; D010088:Oxidoreductases; D020641:Polymorphism, Single Nucleotide; D014168:Transferrin / Q000235:genetics; D055815:Young Adult
chemical_list: D005819:Genetic Markers; C492164:HEPH protein, human; D008565:Membrane Proteins; D014168:Transferrin; D001194:Asbestos; D005293:Ferritins; D007501:Iron; C454461:FTH1 protein, human; D010088:Oxidoreductases