title: Case-only gene-environment interaction between ALAD tagSNPs and occupational lead exposure in prostate cancer.
abstract: BACKGROUND
  Black men have historically had higher blood lead levels than white men in the U.S. and have the highest incidence of prostate cancer in the world. Inorganic lead has been classified as a probable human carcinogen. Lead (Pb) inhibits delta-aminolevulinic acid dehydratase (ALAD), a gene recently implicated in other genitourinary cancers. The ALAD enzyme is involved in the second step of heme biosynthesis and is an endogenous inhibitor of the 26S proteasome, a master system for protein degradation and a current target of cancer therapy.
  
  
  METHODS
  Using a case-only study design, we assessed potential gene-environment (G × E) interactions between lifetime occupational Pb exposure and 11 tagSNPs within ALAD in black (N = 260) and white (N = 343) prostate cancer cases.
  
  
  RESULTS
  Two ALAD tagSNPs in high linkage disequilibrium showed significant interaction with high Pb exposure among black cases (rs818684 interaction odds ratio or IOR = 2.73, 95% CI 1.43-5.22, P = 0.002; rs818689 IOR = 2.20, 95% CI 1.15-4.21, P = 0.017) and an additional tagSNP, rs2761016, showed G × E interaction with low Pb exposure (IOR = 2.08, 95% CI 1.13-3.84, P = 0.019). Further, the variant allele of rs818684 was associated with a higher Gleason grade in those with high Pb exposure among both blacks (OR 3.96, 95% CI 1.01-15.46, P = 0.048) and whites (OR 2.95, 95% CI 1.18-7.39, P = 0.020).
  
  
  CONCLUSIONS
  Genetic variation in ALAD may modify associations between Pb and prostate cancer. Additional studies of ALAD, Pb, and prostate cancer are warranted and should include black men. Prostate 74:637-646, 2014. © 2014 Wiley Periodicals, Inc.
authors: Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan; Population Studies and Prevention Programs, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors: Christine
authors: C
authors: Neslund-Dudas
authors: Albert M
authors: AM
authors: Levin
authors: Andrew
authors: A
authors: Rundle
authors: Jennifer
authors: J
authors: Beebe-Dimmer
authors: Cathryn H
authors: CH
authors: Bock
authors: Nora L
authors: NL
authors: Nock
authors: Michelle
authors: M
authors: Jankowski
authors: Indrani
authors: I
authors: Datta
authors: Richard
authors: R
authors: Krajenta
authors: Q Ping
authors: QP
authors: Dou
authors: Bharati
authors: B
authors: Mitra
authors: Deliang
authors: D
authors: Tang
authors: Benjamin A
authors: BA
authors: Rybicki
mesh_terms: D001741:Black or African American; D000368:Aged; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D007854:Lead / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D000623:Porphobilinogen Synthase / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000209:etiology* / Q000235:genetics; D044465:White People
chemical_list: D007854:Lead; D000623:Porphobilinogen Synthase
keywords: ALAD; African American; delta-aminolevulinic acid dehydratase; heavy metal; lead; occupational exposure; prostate cancer