title: Association between frequency of chromosomal aberrations and cancer risk is not influenced by genetic polymorphisms in GSTM1 and GSTT1.
abstract: BACKGROUND
  The frequency of chromosomal aberrations (CA) in peripheral blood lymphocytes of healthy individuals has been associated with cancer risk. It is presently unclear whether this association is influenced by individual susceptibility factors such as genetic polymorphisms of xenobiotic-metabolizing enzymes.
  
  
  OBJECTIVE
  To evaluate the role of polymorphisms in glutathione S-transferase (GST) M1 (GSTM1) and theta 1 (GSTT1) as effect modifiers of the association between CA and cancer risk.
  
  
  METHODS
  A case-control study was performed pooling data from cytogenetic studies carried out in 1974-1995 in three laboratories in Italy, Norway, and Denmark. A total of 107 cancer cases were retrieved from national registries and matched to 291 controls. The subjects were classified as low, medium, and high by tertile of CA frequency. The data were analyzed by setting up a Bayesian model that included prior information about cancer risk by CA frequency.
  
  
  RESULTS
  The association between CA frequency and cancer risk was confirmed [OR(medium) (odds ratio)(medium) = 1.5, 95% credibility interval (CrI), 0.9-2.5; OR(high) = 2.8, 95% CrI, 1.6-4.6], whereas no effect of the genetic polymorphism was observed. A much stronger association was seen in the Italian subset (OR(high)= 9.4, 95% CrI, 2.6-28.0), which was characterized by a lower technical variability of the cytogenetic analysis. CA level was particularly associated with cancer of the respiratory tract (OR(high)= 6.2, 95% CrI, 1.5-20.0), the genitourinary tract (OR(high) = 4.0, 95% CrI, 1.4-10.0), and the digestive tract (OR(high) = 2.8, 95% CrI, 1.2-5.8).
  
  
  CONCLUSIONS
  Despite the small size of the study groups, our results substantiate the cancer risk predictivity of CA frequency, ruling against a strong modifying effect of GSTM1 and GSTT1 polymorphisms.
authors.affiliation: Department of Biology, Pisa University, Pisa, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Rossi
authors.forename: Inger-Lise
authors.initials: IL
authors.lastname: Hansteen
authors.forename: Camilla Furu
authors.initials: CF
authors.lastname: Skjelbred
authors.forename: Michela
authors.initials: M
authors.lastname: Ballardin
authors.forename: Valentina
authors.initials: V
authors.lastname: Maggini
authors.forename: Elena
authors.initials: E
authors.lastname: Murgia
authors.forename: Antonio
authors.initials: A
authors.lastname: Tomei
authors.forename: Paolo
authors.initials: P
authors.lastname: Viarengo
authors.forename: Lisbeth E
authors.initials: LE
authors.lastname: Knudsen
authors.forename: Roberto
authors.initials: R
authors.lastname: Barale
authors.forename: Hannu
authors.initials: H
authors.lastname: Norppa
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonassi
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012306:Risk
chemical_list: D005982:Glutathione Transferase; C413545:glutathione S-transferase T1