Association between frequency of chromosomal aberrations and cancer risk is not influenced by genetic polymorphisms in GSTM1 and GSTT1.
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.
Rossi
Anna Maria
AM
Department of Biology, Pisa University, Pisa, Italy.
Hansteen
Inger-Lise
IL
Skjelbred
Camilla Furu
CF
Ballardin
Michela
M
Maggini
Valentina
V
Murgia
Elena
E
Tomei
Antonio
A
Viarengo
Paolo
P
Knudsen
Lisbeth E
LE
Barale
Roberto
R
Norppa
Hannu
H
Bonassi
Stefano
S
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
D005982:Glutathione Transferase; C413545:glutathione S-transferase T1