The frequency of micronuclei (MN) in peripheral blood lymphocytes (PBL) is extensively used as a biomarker of chromosomal damage and genome stability in human populations. Much theoretical evidence has been accumulated supporting the causal role of MN induction in cancer development, although prospective cohort studies are needed to validate MN as a cancer risk biomarker. A total of 6718 subjects from of 10 countries, screened in 20 laboratories for MN frequency between 1980 and 2002 in ad hoc studies or routine cytogenetic surveillance, were selected from the database of the HUman MicroNucleus (HUMN) international collaborative project and followed up for cancer incidence or mortality. To standardize for the inter-laboratory variability subjects were classified according to the percentiles of MN distribution within each laboratory as low, medium or high frequency. A significant increase of all cancers incidence was found for subjects in the groups with medium (RR=1.84; 95% CI: 1.28-2.66) and high MN frequency (RR=1.53; 1.04-2.25). The same groups also showed a decreased cancer-free survival, i.e. P=0.001 and P=0.025, respectively. This association was present in all national cohorts and for all major cancer sites, especially urogenital (RR=2.80; 1.17-6.73) and gastro-intestinal cancers (RR=1.74; 1.01-4.71). The results from the present study provide preliminary evidence that MN frequency in PBL is a predictive biomarker of cancer risk within a population of healthy subjects. The current wide-spread use of the MN assay provides a valuable opportunity to apply this assay in the planning and validation of cancer surveillance and prevention programs.
Background: The occurrence of spontaneous tumors in pet animals has been estimated in a few European and North American veterinary cancer registries with dissimilar methodologies and variable reference populations.Objectives: The Animal Tumor Registry (ATR) of Genoa, Italy, was established in 1985 with the aim of estimating the occurrence of spontaneous tumors in dogs.Methods: Six thousand seven hundred and forty-three tumor biopsy specimens were received from local veterinarians in the Municipality of Genoa between 1985 and 2002. Three thousand and three hundred and three (48.9%) biopsy specimen samples were diagnosed as cancer and were coded according to the International Statistical Classification of Diseases (ICD-9).Results: Mammary cancer was the most frequently diagnosed cancer in female dogs, accounting for 70% of all cancer cases. Incidence of all cancers was 99.3 per 100,000 dog-years (95% CI: 93.6-105.1) in male dogs and 272.1 (95% CI: 260.7-283.6) in female dogs. The highest incidence rates were detected for mammary cancer (IR 5 191.8, 95% CI: 182.2-201.4) and for non-Hodgkin's lymphoma (IR 5 22.9, 95% CI: 19.7-26.5) in bitches and for non-Hodgkin's lymphoma (IR 5 19.9, 95% CI: 17.4-22.7) and skin cancer (IR 5 19.1, 95% CI: 16.6-21.8) in male dogs. All cancer IR increased with age ranging between 23.7 (95% CI: 18.4-30.1) and 763.2 (95% CI: 700.4-830.1) in bitches and between 16.5 (95% CI: 12.8-21.1) and 237.6 (95% CI: 209.1-269.0) in male dogs aged 3 years and 49-11 years.Conclusion: This study summarizes the work done by the ATR of Genoa, Italy, between 1985 and 2002. All cancer incidence was 3 times higher in female than in male dogs, a difference explained by the high rate of mammary cancer observed in bitches. Because a biopsy specimen was required to make a cancer diagnosis, cancer rates for internal organs cancers, such as respiratory and digestive tract cancers may have been underestimated in the study population.
Purpose The role of temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal women remains controversial. This systematic review and meta-analysis using individual patient-level data was conducted to better assess the efficacy and safety of this strategy in patients with early breast cancer. Methods The trials in which premenopausal women with early breast cancer were randomly assigned to receive (neo)adjuvant chemotherapy alone or with concurrent GnRHa were eligible for inclusion. Primary end points were premature ovarian insufficiency (POI) rate and post-treatment pregnancy rate. Disease-free survival and overall survival were secondary end points. Because each study represents a cluster, statistical analyses were performed using a random effects model. Results A total of 873 patients from five trials were included. POI rate was 14.1% in the GnRHa group and 30.9% in the control group (adjusted odds ratio, 0.38; 95% CI, 0.26 to 0.57; P < .001). A total of 37 (10.3%) patients had at least one post-treatment pregnancy in the GnRHa group and 20 (5.5%) in the control group (incidence rate ratio, 1.83; 95% CI, 1.06 to 3.15; P = .030). No significant differences in disease-free survival (adjusted hazard ratio, 1.01; 95% CI, 0.72 to 1.42; P = .999) and overall survival (adjusted hazard ratio, 0.67; 95% CI, 0.42 to 1.06; P = .083) were observed between groups. Conclusion Our findings provide evidence for the efficacy and safety of temporary ovarian suppression with GnRHa during chemotherapy as an available option to reduce the likelihood of chemotherapy-induced POI and potentially improve future fertility in premenopausal patients with early breast cancer.
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