title: Occupational exposure to polycyclic aromatic hydrocarbons influenced neither the frequency nor the spectrum of FGFR3 mutations in bladder urothelial carcinoma.
abstract: Occupational exposure to polycyclic aromatic hydrocarbons (PAH) is associated with an increased risk of urothelial carcinoma (UC). FGFR3 is found mutated in about 70% of Ta tumors, which represent the major group at diagnosis. The influence of PAH on FGFR3 mutations and whether it is related to the emergence or shaping of these mutations is not yet known. We investigated the influence of occupational PAH on the frequency and spectrum of FGFR3 mutations. We included on 170 primary urothelial tumors from five hospitals from France. Patients (median age, 64 yr) were interviewed to gather data on occupational exposure to PAH, revealing 104 non- and possibly PAH exposed patients, 66 probably and definitely exposed patients. Tumors were classified as follows: 75 pTa, 52 pT1, and 43 > or =pT2. Tumor grades were as follows: 6 low malignant potential neoplasms (LMPN) and 41 low-grade and 123 high-grade carcinomas. The SnaPshot method was used to screen for the following FGFR3 mutations: R248C, S249C, G372C, Y375C, A393E, K652E, K652Q, K652M, and K652T. Occupational PAH exposure was not associated with a particular stage or grade of tumors. Thirty-nine percent of the tumors harbored FGFR3 mutations. After adjustment for smoking, occupational exposure to PAH did not influence the frequency [OR, 1.10; 95% CI, 0.78-1.52], or spectrum of FGFR3 mutations. Occupational exposure to PAH influenced neither the frequency nor the spectrum of FGFR3 mutations and there was no direct relationship between these mutations and this occupational hazard.
authors.affiliation: INSERM, Créteil, France.
authors.forename: Ashraf A
authors.initials: AA
authors.lastname: Bakkar
authors.forename: Yves
authors.initials: Y
authors.lastname: Allory
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Iwatsubo
authors.forename: Sixtina Gil Diez
authors.initials: SG
authors.lastname: de Medina
authors.forename: Pascale
authors.initials: P
authors.lastname: Maille
authors.forename: Nathalie
authors.initials: N
authors.lastname: Khreich
authors.forename: Audrey
authors.initials: A
authors.lastname: Riou
authors.forename: Karen
authors.initials: K
authors.lastname: Leroy
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Vordos
authors.forename: Claude C
authors.initials: CC
authors.lastname: Abbou
authors.forename: Pascal
authors.initials: P
authors.lastname: Andujar
authors.forename: Thierry
authors.initials: T
authors.lastname: Billebaud
authors.forename: Soizick
authors.initials: S
authors.lastname: Chammings
authors.forename: Françoise
authors.initials: F
authors.lastname: Conso
authors.forename: Alexandre
authors.initials: A
authors.lastname: De La Taille
authors.forename: Eric
authors.initials: E
authors.lastname: Fontaine
authors.forename: Bernard
authors.initials: B
authors.lastname: Gattegno
authors.forename: Vincent
authors.initials: V
authors.lastname: Ravery
authors.forename: Mathilde
authors.initials: M
authors.lastname: Sibony
authors.forename: François
authors.initials: F
authors.lastname: Radvanyi
authors.forename: Dominique K
authors.initials: DK
authors.lastname: Chopin
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Pairon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016273:Occupational Exposure / Q000032:analysis*; D011084:Polycyclic Aromatic Hydrocarbons / Q000506:poisoning*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology
chemical_list: D011084:Polycyclic Aromatic Hydrocarbons; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3