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Anna Maria Rossi,¹* Inger-Lise Hansteen,²* Camilla Furu Skjelbred,² Michela Ballardin,¹ Valentina Maggini,¹ Elena Murgia,¹ Antonio Tomei,¹ Paolo Viarengo,³ Lisbeth E. Knudsen,⁴ Roberto Barale,¹ Hannu Norppa,⁵ and Stefano Bonassi ⁶

¹Department of Biology, Pisa University, Pisa, Italy, ²Department of Laboratory Medicine, Section of Medical Genetics, Telemark Hospital, Skien, Norway; ³Department of Aerospace Engineering, University of Naples Federico II, Naples, Italy; ⁴Environmental Health, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark; ⁵New Technologies and Risks, Work Environment Development, Finnish Institute of Occupational Health, Helsinki, Finland; ⁶Unit of Molecular Epidemiology, National Cancer Research Institute, Genoa, Italy

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.

Objectives: 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.

Key words: Bayesian, biomarker, cancer risk, case–control study, chromosomal aberration, genetic polymorphism, glutathione S-transferase, GSTM1, GSTT1, Monte Carlo Markov Chain. Environ Health Perspect 117:203–208 (2009) . doi:10.1289/ehp.11769 available via http://dx.doi.org/ [Online September 2008]

Address correspondence to S. Bonassi, Unit of Molecular Epidemiology, National Cancer Research Institute, Largo Rosanna Benzi, 10, 16132 Genoa, Italy. Telephone: 390 10 5600924. Fax: 390 10-5600501. E-mail: stefano.bonassi@istge.it.

*These two authors contributed equally to the present study.

This work was supported by grants from the European Union 5th FP (QLRT-2000-00628) and its extension (QLK4-CT-2002-02831) , the Associazione Italiana per la Ricerca sul Cancro (AIRC) , the Italian Ministry of Health, the Italian Space Agency (ASI) , the Telemark Hospital (Research and Development) , the Fondazione Buzzi-Unicem per la Ricerca sul Mesotelioma, Casale (Italy) , the Danish National Programme of Environmental Health Research on Cancer (0-302-02-4/2) , and the Finnish Work Environment Fund.

The Cancer Registry of Norway is not responsible for the analysis or interpretation of the data presented.

The authors declare they have no competing financial interests.

Received 6 June 2008 ; accepted 16 September 2008.