No abstract

Molecular mutation spectra induced by N-ethyl-N-nitrosourea have been obtained in several organisms and test systems, frequently showing different results. In Drosophila melanogaster this spectrum has been analyzed in postmeiotic stages, resulting in good agreement between the adduct spectrum and mutational events, the majority being GC-->AT transitions (61%). However, when collecting data about in vivo ENU-induced mutations in mouse germ cell stages mostly damage at A:T sites (89%) was observed. In this work we analyze the molecular spectrum induced with ENU in pre-meiotic repair-active male germ cells of D.melanogaster, using the specific locus test (SLT) with the vermilion locus as target. Results show that the most mutagenic sites in spermatogonial stem cells of Drosophila are A:T pairs (85%), with AT-->TA transversions (50%) and AT-->GC transitions (35%) as the most frequent mutations. Differences from the post-meiotic spectrum may be explained by the active repair of some adducts, such as O6-ethylguanine and N-alkyl-induced abasic sites. In addition, these results show the relevance of the minor lesions O4-ethylthymine and O2-ethylthymine in the production of mutations, as a consequence of their poor repair. Finally, since there is a striking similarity to the ENU-induced mutation spectrum in mouse, these results reveal that Drosophila continues to be an excellent model system.

Breast cancer (BC) survivors have an increased risk of developing second primary cancer (SPC). The aim of this study was to detect and compare SPC predictors linked to the host, the first BC and its treatment. Two hundred and seventeen patients with a nonbreast SPC and 465 matched controls, nested in the cohort of BC patients diagnosed in a Spanish region between 1975 and 2003, were involved in a case-control study. The Tumour Registry database provided information about the host, BC and its treatment factors. Their contribution to the risk of developing SPC was measured by means of a conditional logistic regression. After controlling for differences between cases and controls at baseline, obesity [odds ratio (OR): 7.48; 95% confidence interval (CI): 1.25-44.88], smoking (OR: 3.16; 95% CI: 1.23-8.15), high blood pressure (OR: 1.68; 95% CI: 1.04-2.71) and having first-degree relatives suffering from cancer (OR: 1.69; 95% CI: 1.05-2.72) were the best SPC predictors. The risk of SPC increases by 1% per month of survival from BC (OR: 1.01; 95% CI: 1.007-1.012), while having metastases (OR: 0.23; 95% CI: 0.14-0.37) and being premenopausal at diagnosis of the BC (OR: 0.44; 95% CI: 0.247-0.792) diminish the risk, probably decreasing survival. The treatments were the regression model's worst predictors. Controlling modifiable factors linked to lifestyle such as obesity and smoking is essential to prevent SPC in survivors of BC. Health education to remove persistent risk factors should be included in the treatment protocol of BC patients, because they are important predictors of SPC.

No abstract

This study was set to look for associations between the sites of the first and subsequent tumours in patients with multiple primary cancer (MPC) diagnosed from 1975 to 2002 in the reference hospital of a Spanish northern region, and propose prevention strategies. Patient and tumour variables were measured. Crude and standardized incidence rates per 100 000 inhabitants were obtained, and the association between MPC incidence and time was analysed by means of lineal regression. Relative risks were calculated to analyse associations between tumour sites. A total of 2737 MPC cases were registered (male/female ratio = 2). The percentage of MPC with respect to the total cancer increased from 1.78% in the 1975-1979 period to 7.08% in the 2000-2002 period (R(2) = 0.92; P = 0.003). Great increase of incidence by time was found (R(2) = 0.90; P = 0.004). Breast, prostate and bladder cancers increase risk of second tumour in female genital organs [RR 4.78 (3.84-5.93)], urinary system [RR 3.69 (2.89-4.69)] and male genital organs [RR 3.76 (2.84-4.69)] respectively. The MPC incidence is increasing. Interventions for MPC prevention, according to the European Code against Cancer, should be implemented early after the first cancer principally if patients suffer breast, bladder, prostate, larynx and colon cancers.