title: Aromatic DNA adducts and number of lung cancer risk alleles in Map-Ta-Phut Industrial Estate workers and nearby residents.
abstract: The Map-Ta-Phut Industrial Estate (MIE) in Rayong, Thailand, is the location of one of the largest industrial complexes in southeastern Asia. The MIE complex produces a mixture of air pollutants, including polycyclic aromatic hydrocarbons, compounds capable to induce the generation of DNA adducts. DNA adducts are considered to be a biomarker of carcinogen exposure; however, its production can be modulated by genetic susceptibility. Thus, we analysed the influence of EPHX1 His139Arg (A>G, rs2234922) and NQO1 Pro187Ser (C>T, rs1800566) involved in the metabolism of polycyclic aromatic hydrocarbons; MnSOD(2) Val16Ala (C>T, rs1799725) a gene that acts against the free radical generation; APE1/Ref-1 Asp148Glu (T>G, rs3136820) a gene involved in the repair of DNA, and in the control of cell-cycle and apoptosis on leucocyte DNA adducts in 77 MIE workers, 69 Map-Ta-Phut residents, and 50 rural controls, Rayong, Thailand. We searched for associations with the 'sum of at-risk alleles' by combining the variant alleles of EPHX1, NQO1 and MnSOD(2) together with the wild-type allele of APE1, since they appeared to influence lung cancer risk. Although our findings revealed significant associations between DNA adducts and the EPHX1 His139Arg and NQO1 Pro187Ser polymorphisms, the combination of at-risk alleles was found to affect DNA damage much stronger. DNA adducts were significantly increased in the individuals bearing 4 and ≥ 5 at-risk alleles [mean ratio (MR) = 1.55, 95% CI 1.10-2.18, P = 0.012, and MR = 2.11, 95% CI 1.27-3.51, P = 0.004, respectively)]. After correction for residence/employment categorisation, a significant increment was present in the MIE workers with ≥ 5 alleles (MR = 2.88, 95% CI 1.46-5.71, P = 0.003). Our data indicate relationships between the generation of DNA adducts and the enzymatic activities of EPHX and NQO1. The combination of unfavourable genetic variants seems to determine the individuals' susceptibility, rather than a single polymorphism.
authors.affiliation: Cancer Risk Factor Branch, Cancer Prevention and Research Institute, Florence, Italy. m.peluso@ispo.toscana.it
authors.forename: Marco
authors.initials: M
authors.lastname: Peluso
authors.forename: Petcharin
authors.initials: P
authors.lastname: Srivatanakul
authors.forename: Adisorn
authors.initials: A
authors.lastname: Jedpiyawongse
authors.forename: Suleeporn
authors.initials: S
authors.lastname: Sangrajrang
authors.forename: Armelle
authors.initials: A
authors.lastname: Munnia
authors.forename: Sara
authors.initials: S
authors.lastname: Piro
authors.forename: Marcello
authors.initials: M
authors.lastname: Ceppi
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Roger W L
authors.initials: RW
authors.lastname: Godschalk
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: van Schooten
mesh_terms: D000328:Adult; D002273:Carcinogens / Q000633:toxicity; D016022:Case-Control Studies; D018736:DNA Adducts / Q000032:analysis*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D004781:Environmental Exposure / Q000009:adverse effects; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D016273:Occupational Exposure / Q000009:adverse effects*; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity; D020641:Polymorphism, Single Nucleotide; D013482:Superoxide Dismutase / Q000235:genetics*; D013785:Thailand; D000099156:Superoxide Dismutase 2
chemical_list: D002273:Carcinogens; D018736:DNA Adducts; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004851:Epoxide Hydrolases; D016660:NAD(P)H Dehydrogenase (Quinone); D011084:Polycyclic Aromatic Hydrocarbons; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C447479:NQO1 protein, human; C522330:EPHX1 protein, human; C085108:APEX1 protein, human