Carcinogenesis Advance Access published online on December 19, 2003
Carcinogenesis, doi:10.1093/carcin/bgh057
© 2003 by Oxford University Press
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MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
1 Department of Experimental Pathology and Oncology, University of Florence
* Corresponding author. E-mail: a.seniori{at}cspo.it.
Received 3 October 2003
; revised 2 December 2003
; accepted 9 December 2003
Mutations of the N- and K-ras genes occur in approximately 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 likely 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 three year period, a 111 Acute Myeloid Leukaemia patients were enrolled. All the patients were interviewed by 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. 14 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 9 exposed cases; the odds ratio, adjusted by age, sex and previous X-ray and/or chemo-therapy was 2.8 (95% confidence intervals: 0.9-9.0). When considering only subjects with 2 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 chemo-therapy was 16.2 (95% confidence intervals: 1.8-755.9); when only subjects with 2 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/chemo-therapy or with exposure to chemical agents in the work environment.
Ras gene mutations in patients with Acute Myeloid Leukaemia and exposure to chemical agents
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
6 ISI Foundation and Department of Genetics, Biology and Biochemistry, University of Turin
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