title: Polymorphisms in the DNA repair enzyme XPD are associated with increased levels of PAH-DNA adducts in a case-control study of breast cancer.
abstract: We present findings on the associations between DNA adduct levels in breast tissue, risk of breast cancer, and polymorphisms in the DNA repair enzyme XPD. Breast cancer cases, benign breast disease (BBD) controls, and healthy controls were enrolled. Polycyclic aromatic hydrocarbons (PAH)-DNA adduct levels were measured by immunohistochemistry in breast tissue samples from cases and BBD controls. XPD polymorphisms at codons 312 and 751 was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis using white blood cell DNA. Neither of the polymorphisms were associated with case-control status, both in comparisons of cases and BBD controls, and cases and healthy controls. XPD polymorphisms at codons 312 and 751 were associated with higher levels of PAH-DNA in tumor tissue from breast cancer cases. Subjects with an Asp/Asn or Asn/Asn polymorphic genotype in codon 312 of XPD had elevated levels of PAH-DNA adducts compared to subjects with the Asp/Asp genotype (0.55 optical density (OD) v.s. 0.33 OD, p < 0.01). PAH-DNA adducts were associated with increasing copy number of the Gln allele for the codon 751 polymorphism (p for trend <0.01). Among subjects with the Asp/Asn or Asn/Asn genotype at codon 312, adduct levels were higher in tumor tissue compared to tissue from BBD controls (0.55 OD v.s. 0.36 OD, p = 0.003). Among subjects with the Gln/Gln genotype at codon 751 adduct levels were higher in tumor tissue compared to tissue from BBD controls (0.68 OD v.s. 0.40 OD, p = 0.01). The trend of increasing PAH-DNA adduct levels with either the Asn/Asn or Gln/Gln genotype was greater in tumor tissue than the trend in BBD control tissue.
authors.affiliation: Department of Environmental Health Sciences, Joseph L. Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
authors.forename: Deliang
authors.initials: D
authors.lastname: Tang
authors.forename: Stan
authors.initials: S
authors.lastname: Cho
authors.forename: Andrew
authors.initials: A
authors.lastname: Rundle
authors.forename: Senqing
authors.initials: S
authors.lastname: Chen
authors.forename: David
authors.initials: D
authors.lastname: Phillips
authors.forename: Jingzhi
authors.initials: J
authors.lastname: Zhou
authors.forename: Yanzhi
authors.initials: Y
authors.lastname: Hsu
authors.forename: Freya
authors.initials: F
authors.lastname: Schnabel
authors.forename: Alison
authors.initials: A
authors.lastname: Estabrook
authors.forename: Frederica P
authors.initials: FP
authors.lastname: Perera
mesh_terms: D000704:Analysis of Variance; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics*; D016022:Case-Control Studies; D018736:DNA Adducts / Q000032:analysis*; D004265:DNA Helicases; D004260:DNA Repair; D004268:DNA-Binding Proteins; D005260:Female; D005838:Genotype; D006801:Humans; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis*; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D014157:Transcription Factors; D051759:Xeroderma Pigmentosum Group D Protein
chemical_list: D018736:DNA Adducts; D004268:DNA-Binding Proteins; D011084:Polycyclic Aromatic Hydrocarbons; D011506:Proteins; D014157:Transcription Factors; C095911:polycyclic aromatic hydrocarbons-DNA adduct; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human