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Carcinogenesis Advance Access originally published online on December 19, 2003
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Carcinogenesis, Vol. 25, No. 5, 749-755, May 2004
Carcinogenesis vol.25 no.5 © Oxford University Press 2004; all rights reserved.


ARTICLE

Ras gene mutations in patients with acute myeloid leukaemia and exposure to chemical agents

Emanuela Barletta1, Giuseppe Gorini2, Paolo Vineis3, Lucia Miligi2, Laura Davico4, Gabriele Mugnai1, Stefania Ciolli5, Franco Leoni5, Marilena Bertini4, Giuseppe Matullo6 and Adele Seniori Costantini2,7

1 Department of Experimental Pathology and Oncology, University of Florence, 2 Centre for Study and Prevention of Cancer—Unit of Occupational and Environmental Epidemiology, Florence, 3 Department of Biomedical Sciences and Human Oncology, AO San Giovanni Battista/University of Turin, 4 Department of Haematology, AO San Giovanni Battista, Turin, 5 Department of Haematology Careggi University Hospital, Florence and 6 ISI Foundation and Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy

7 To whom correspondence should be addressed Email: a.seniori{at}cspo.it

Mutations of the N- and K-ras genes occur in ~15–30% of acute myeloid leukaemia patients. The role of the oncogenic ras in leukaemogenesis remains unclear. Few studies have revealed that mutations in the ras oncogene family are more probably found in acute myeloid leukaemia patients with previous exposure to toxic agents. A case–case study was conducted in the areas of Florence and Turin, Italy, to investigate whether the presence of N- and K-ras mutations in acute myeloid leukaemia patients was related to a higher frequency of exposure to chemicals. During a 3-year period, 111 acute myeloid leukaemia patients were enrolled. All the patients were interviewed using a semi-structured questionnaire collecting data on residential history, occupation, personal habits and pathological history. The presence of N- and K-ras mutations was analysed by amplification and synthetic oligonucleotide probes and by the so-called polymerase chain reaction amplification for specific alleles technique. A total of 34 (30.6%) patients were found to harbour ras mutations in N-ras and/or K-ras. Fourteen patients (12.6%) had a single ras mutation and 20 patients (18%) had two ras mutations. A positive association between a priori at risk jobs and ras mutations was found, based on nine exposed cases; the odds ratio, adjusted by age, sex and previous X-ray and/or chemotherapy was 2.8 (95% confidence intervals: 0.9–9.0). When considering only subjects with two ras mutations the odds ratio was 4.8 (95% confidence intervals: 1.2–18.8). The odds ratio for a previous X-ray and/or chemotherapy was 16.2 (95% confidence intervals: 1.8–755.9); when only subjects with two ras mutations were considered, the odds ratio was 26.1 (95% confidence intervals: 2.5–1248.9). In conclusion, our data suggest that ras oncogene mutations might identify a group of leukaemia in people with previous X-ray/chemotherapy or with exposure to chemical agents in the work environment.


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